Utility of incorporating next-generation sequencing (NGS) in an Asian non-small cell lung cancer (NSCLC) population: Incremental yield of actionable alterations and cost-effectiveness analysis
Utility of incorporating next-generation sequencing (NGS) in an Asian non-small cell lung cancer (NSCLC) population: Incremental yield of actionable alterations and cost-effectiveness analysis
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DOI：
10.1016/j.lungcan.2019.11.022
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发表时间：
2020-01-01
期刊：
影响因子：
5.3
通讯作者：
Tan, Daniel S. W.
中科院分区：
文献类型：
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作者：
Tan, Aaron C.;Lai, Gillianne G. Y.;Tan, Daniel S. W.
目的：非小细胞肺癌（NSCLC）的治疗相关生物标志物列表不断扩大，诊断时的分子谱分析至关重要。在从小活检中缩放传统的单一生物标志物测定中的组织磨损是越来越多地遇到的问题。我们试图比较有针对性的下一代测序（NGS）面板与传统检测的性能，并将突变景观与新加坡患者的PD-L1状态相关联。材料和方法：我们确定了2016年1月至2017年9月之间诊断的连续患者，标准分子检测后残留组织。使用靶向NGS组检测组织样本的DNA改变（29个选定的基因，包括BRAF、EGFR、ERBB 2和TP 53）和RNA融合组（ALK、ROS 1和RET）。还进行了PD-L1免疫组织化学。结果：共对174份样本进行了评估：PD-L1（n = 169）、NGS DNA panel（n = 173）和RNA融合（n = 119）检测。中位年龄为68岁，53%为男性，58%从不吸烟，85%为中国人，66例为IV期疾病，95%为腺癌组织学。在DNA上具有NGS谱的患者中，发现EGFR（56%）、KRAS（14%）、BRAF（2%）和ERBB 2（1%）突变。RNA融合检测显示ALK（6%）、RET（3%）和ROS 1（1%）融合。成本效益分析表明，与EGFR阴性患者的序贯检测相比，前期NGS检测将导致额外1%的患者出现可操作的靶向治疗改变，而不会显著增加检测成本或周转时间。这项研究表明，即使在EGFR突变占主导地位的人群中，前期NGS也代表了一种可行的，与序贯检测策略相比，这是一种具有成本效益的诊断分子谱分析方法。我们的研究结果支持在亚洲非鳞状NSCLC中实施诊断性NGS，以使患者获得最合适的个性化治疗。
Objectives: There is an expanding list of therapeutically relevant biomarkers for non-small cell lung cancer (NSCLC), and molecular profiling at diagnosis is paramount. Tissue attrition in scaling traditional single biomarker assays from small biopsies is an increasingly encountered problem. We sought to compare the performance of targeted next-generation sequencing (NGS) panels with traditional assays and correlate the mutational landscape with PD-L1 status in Singaporean patients.Materials and methods: We identified consecutive patients diagnosed between Jan 2016 to Sep 2017 with residual tissue after standard molecular testing. Tissue samples were tested using a targeted NGS panel for DNA alterations (29 selected genes including BRAF, EGFR, ERBB2 and TP53) and an RNA fusion panel (ALK, ROS1 and RET). PD-L1 immunohistochemistry was also performed. A cost-effectiveness analysis of NGS compared to standard molecular testing was conducted.Results: A total of 174 samples were evaluated: PD-L1 (n = 169), NGS DNA panel (n = 173) and RNA fusion (n = 119) testing. Median age was 68 years, 53 % were male, 58 % were never smokers, 85 % were Chinese, 66 had stage IV disease and 95 % had adenocarcinoma histology. In patients profiled with NGS on DNA, EGFR (56 %), KRAS (14 %), BRAF (2 %) and ERBB2 (1 %) mutations were found. RNA fusion testing revealed fusions in ALK (6 %), RET (3 %) and ROS1 (1 %). Cost-effectiveness analysis demonstrated that compared to sequential testing in EGFR negative patients, upfront NGS testing would result in an additional 1 % of patients with actionable alterations for targeted therapy being identified without significant increases in testing cost or turnaround time.Conclusions: This study demonstrates that even in an EGFR mutant predominant population, upfront NGS represents a feasible, cost-effective method of diagnostic molecular profiling compared with sequential testing strategies. Our results support the implementation of diagnostic NGS in non-squamous NSCLC in Asia to allow patients access to the most appropriate personalized therapy.