Fernandes Maria Gabriela O, Cruz-Martins Natália, Souto Moura Conceição, Guimarães Susana, Pereira Reis Joana, Justino Ana, Pina Maria João, Magalhães Adriana, Queiroga Henrique, Machado José Carlos, Hespanhol Venceslau, Costa José Luis
Pulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal.
Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal.
Cancers (Basel). 2021 May 30;13(11):2707. doi: 10.3390/cancers13112707.
Analysis of circulating tumor DNA (ctDNA) has remarkable potential as a non-invasive lung cancer molecular diagnostic method. This prospective study addressed the clinical value of a targeted-gene amplicon-based plasma next-generation sequencing (NGS) assay to detect actionable mutations in ctDNA in patients with newly diagnosed advanced lung adenocarcinoma.
ctDNA test performance and concordance with tissue NGS were determined, and the correlation between ctDNA findings, clinical features, and clinical outcomes was evaluated in 115 patients with paired plasma and tissue samples.
Targeted-gene NGS-based ctDNA and NGS-based tissue analysis detected 54 and 63 genomic alterations, respectively; 11 patients presented co-mutations, totalizing 66 hotspot mutations detected, 51 on both tissue and plasma, 12 exclusively on tissue, and 3 exclusively on plasma. NGS-based ctDNA revealed a diagnostic performance with 81.0% sensitivity, 95.3% specificity, 94.4% PPV, 83.6% NPV, test accuracy of 88.2%, and Cohen's Kappa 0.764. PFS and OS assessed by both assays did not significantly differ. Detection of ctDNA alterations was statistically associated with metastatic disease ( = 0.013), extra-thoracic metastasis ( = 0.004) and the number of organs involved ( = 0.010).
This study highlights the potential use of ctDNA for mutation detection in newly diagnosed NSCLC patients due to its high accuracy and correlation with clinical outcomes.
循环肿瘤DNA（ctDNA）分析作为一种非侵入性肺癌分子诊断方法具有显著潜力。这项前瞻性研究探讨了基于靶向基因扩增子的血浆下一代测序（NGS）检测方法在新诊断的晚期肺腺癌患者中检测ctDNA中可操作突变的临床价值。
确定ctDNA检测性能及其与组织NGS的一致性，并在115例有配对血浆和组织样本的患者中评估ctDNA检测结果、临床特征和临床结局之间的相关性。
基于靶向基因NGS的ctDNA检测和基于NGS的组织分析分别检测到54个和63个基因组改变；11例患者存在共突变，共检测到66个热点突变，其中51个在组织和血浆中均检测到，12个仅在组织中检测到，3个仅在血浆中检测到。基于NGS的ctDNA检测显示出诊断性能，敏感性为81.0%，特异性为95.3%，阳性预测值为94.4%，阴性预测值为83.6%，检测准确率为88.2%，Cohen's Kappa为0.764。两种检测方法评估的无进展生存期（PFS）和总生存期（OS）无显著差异。ctDNA改变的检测与转移性疾病（P = 0.013）、胸外转移（P = 0.004）和受累器官数量（P = 0.010）在统计学上相关。
本研究强调了ctDNA因其高准确性以及与临床结局的相关性，在新诊断的非小细胞肺癌患者中用于突变检测的潜在用途。
