背景:推荐靶向下一代测序(NGS)用于筛选非小细胞肺癌(NSCLC)患者的可操作基因组改变(GA)。我们确定了使用TruSight™肿瘤学500(TSO500)在200例连续NSCLC患者中检测可操作的GA的可行性。
方法:在Illumina®NextSeq550仪器上对DNA和RNA进行测序,并使用TSO500Docker管道进行处理。根据针对癌基因成瘾的NSCLC的欧洲医学肿瘤学会(ESMO)指南,在分子肿瘤委员会中定义了临床可操作性。根据存在可用药的GAs和靶向治疗的治疗来估计总生存期(OS)。
结果:大多数患者为男性(69.5%)和曾经或现在的吸烟者(86.5%)。中位年龄为64岁。最常见的组织学类型和肿瘤分期是肺腺癌(81%)和IV期(64%),分别。在大多数患者(93.5%)中,测序是可行的,在26.5%的患者中发现了可操作的GA。在单基因测试和TSO500NGS面板之间观察到高度一致性。与没有可吸毒的GA的患者相比,携带可吸毒的GA并接受靶向治疗的患者获得了更长的OS。相反,与驱动阴性患者相比,未接受靶向治疗的可用药GA患者的OS有缩短趋势.
结论:使用TSO500组的杂交捕获测序对于分析NSCLC患者的临床样本是可行的,并且是筛选可操作的GAs的有效工具。
BACKGROUND: Targeted next-generation sequencing (NGS) is recommended to screen actionable genomic alterations (GAs) in patients with non-small-cell lung cancer (NSCLC). We determined the feasibility to detect actionable GAs using TruSight™ Oncology 500 (TSO500) in 200 consecutive patients with NSCLC.
METHODS: DNA and RNA were sequenced on an Illumina® NextSeq 550 instrument and processed using the TSO500 Docker pipeline. Clinical actionability was defined within the molecular tumour board following European Society for Medical Oncology (ESMO) guidelines for oncogene-addicted NSCLC. Overall survival (OS) was estimated as per the presence of druggable GAs and treatment with targeted therapy.
RESULTS: Most patients were males (69.5%) and former or current smokers (86.5%). Median age was 64 years. The most common histological type and tumour stage were lung adenocarcinoma (81%) and stage IV (64%), respectively. Sequencing was feasible in most patients (93.5%) and actionable GAs were found in 26.5% of patients. A high concordance was observed between single-gene testing and TSO500 NGS panel. Patients harbouring druggable GAs and receiving targeted therapy achieved longer OS compared to patients without druggable GAs. Conversely, patients with druggable GAs not receiving targeted therapy had a trend toward shorter OS compared with driver-negative patients.
CONCLUSIONS: Hybrid capture sequencing using TSO500 panel is feasible to analyse clinical samples from patients with NSCLC and is an efficient tool for screening actionable GAs.