Background: The use of next-generation sequencing (NGS) in liquid biopsy allows for a comprehensive molecular assessment of circulating tumor DNA (ctDNA) in patients with advanced malignancies. This approach facilitates the detection of clinically relevant mutations linked to prognosis and enables a personalized therapeutic strategy. The objective of this study was to assess the mutational landscape of ctDNA using NGS in patients with advanced non-small cell lung cancer (NSCLC), examine its relationship with clinical and molecular variables, and explore its association with overall survival (OS). Methods: We performed a retrospective observational study including 78 individuals with metastatic NSCLC treated at Arnau de Vilanova Hospital between 2019 and 2021. Plasma samples were analyzed using the AVENIO NGS platform, which targets the exons of 77 genes. Statistical analyses were conducted using SPSS version 25, applying a 95% confidence level. Results: A total of 143 genomic alterations were identified in the study population. NGS-directed therapies were initiated in eight patients (10.25%), including EGFR (n = 5), KRAS (n = 2), and BRCA1 (n = 1). The concordance rate between tissue and plasma NGS for EGFR alterations was 57.02%, with mutation frequencies of 11.4% in tissue and 6.5% in plasma. No BRAF mutations were detected by plasma analysis, despite being present in 4.3% of tissue samples. Patients receiving NGS-informed targeted therapy showed a numerically improved OS compared to those who did not, although this difference did not reach statistical significance (p= 0.34). Conclusions: Liquid biopsy based on NGS represents a reliable and minimally invasive approach for the genomic characterization of advanced NSCLC. In this real-world cohort, ctDNA profiling enabled the identification of actionable alterations in a relevant proportion of patients, supporting its integration into routine clinical practice for therapeutic decision-making.
背景：在液体活检中应用下一代测序技术，可对晚期恶性肿瘤患者的循环肿瘤DNA进行全面分子评估。该方法有助于检测与预后相关的临床意义突变，并支持个体化治疗策略的制定。本研究旨在利用NGS技术评估晚期非小细胞肺癌患者ctDNA的突变谱，分析其与临床及分子变量的关联性，并探讨其与总生存期的关系。方法：我们开展了一项回顾性观察研究，纳入2019年至2021年间在Arnau de Vilanova医院接受治疗的78例转移性NSCLC患者。使用靶向77个基因外显子区域的AVENIO NGS平台对血浆样本进行分析。采用SPSS 25版统计软件进行数据分析，置信水平设定为95%。结果：在研究人群中总计检测到143个基因组变异。8例患者（10.25%）根据NGS结果启动了靶向治疗，涉及EGFR（5例）、KRAS（2例）和BRCA1（1例）。组织与血浆NGS检测EGFR变异的一致性率为57.02%，组织样本突变频率为11.4%，血浆样本为6.5%。血浆分析未检出BRAF突变，而组织样本中该突变检出率为4.3%。接受NGS指导靶向治疗的患者总生存期在数值上优于未接受者，但差异未达到统计学显著性（p=0.34）。结论：基于NGS的液体活检是晚期NSCLC基因组特征分析的可靠微创方法。在此真实世界队列中，ctDNA谱分析能够在相当比例患者中识别可干预的基因变异，支持将该技术整合到常规临床实践中以指导治疗决策。
肿瘤(癌症)患者之家