Real-world utility of next-generation sequencing for targeted gene analysis and its application to treatment in lung adenocarcinoma

IF 3.1 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2021-05-07 DOI:10.1002/cam4.3874

Jwa Hoon Kim, Shinkyo Yoon, Dae Ho Lee, Se Jin Jang, Sung-Min Chun, Sang-We Kim

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引用次数: 8

Abstract

Purpose

This study investigated the clinical utility of next-generation sequencing (NGS) for detection of genetic alterations and its implications on treatment of lung adenocarcinoma in real-world practice.

Patients and Methods

Data were reviewed for 391 patients with lung adenocarcinoma who underwent NGS between March 2017 and October 2018. Formalin-fixed, paraffin-embedded archival samples were used for performing NGS targeting 382 genes, including all exons of 199 genes, 184 hotspots, and the partial introns of 8 genes often rearranged in cancer. Survival analysis was performed for stage IV disease.

Results

Among the 391 patients, at least one actionable mutation was identified in 294 patients (75.2%). The most commonly mutated gene was EGFR (n = 130, 33.2%), involving EGFR exon 19 deletion (n = 48, 12.3%), L858R (n = 47, 12%), and others (n = 35, 9%), followed by KRAS (n = 48, 12.3%), ALK (n = 40, 10.2%), RET (6%), MET (3%), ROS-1 (3%), and BRAF (2%) mutations. TP53 (46.9%) and CDKN2A (12.6%) mutations were common co-mutations in patients with AMs. With a median follow-up duration of 16.8 months, median overall survival was 36.8 months in patients with stage IV disease. Patients treated with the corresponding targeted therapy for AMs based on NGS reports lived significantly longer than those not treated with such therapy (p < 0.001). After multivariate analysis, targeted therapy for AM was a significantly favorable factor for survival (AM without targeted therapy vs. AM with targeted therapy, hazard ratio 2.58, 95% confidence interval 1.57–4.25; p < 0.001).

Conclusion

This study revealed that AMs could be comparably detected using NGS. Based on these NGS results, a suitable targeted therapy can be selected, which may improve survival in patients with lung adenocarcinoma. This NGS-based approach is useful in real-world practice to provide guidance when selecting targeted therapy.

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新一代测序在靶向基因分析中的实际应用及其在肺腺癌治疗中的应用

目的研究新一代测序(NGS)检测肺腺癌基因改变的临床应用及其对肺腺癌治疗的意义。患者和方法回顾了2017年3月至2018年10月期间接受NGS治疗的391例肺腺癌患者的数据。采用福尔马林固定石蜡包埋档案样本，对382个基因进行NGS，其中包括199个基因的全部外显子、184个热点，以及8个癌症中常重排基因的部分内含子。对IV期疾病进行生存分析。结果在391例患者中，294例(75.2%)患者至少鉴定出一种可操作突变。最常见的突变基因是EGFR (n = 130, 33.2%)，包括EGFR外显子19缺失(n = 48, 12.3%)、L858R (n = 47, 12%)和其他基因(n = 35, 9%)，其次是KRAS (n = 48, 12.3%)、ALK (n = 40, 10.2%)、RET(6%)、MET(3%)、ROS-1(3%)和BRAF(2%)突变。TP53(46.9%)和CDKN2A(12.6%)突变是AMs患者常见的共突变。IV期疾病患者的中位随访时间为16.8个月，中位总生存期为36.8个月。根据NGS报告，接受相应靶向治疗的AMs患者的寿命明显长于未接受此类治疗的患者(p <0.001)。多因素分析后，AM的靶向治疗是显著有利的生存因素(无靶向治疗AM vs有靶向治疗AM，风险比2.58,95%可信区间1.57-4.25;p & lt;0.001)。结论采用NGS法可较好地检测出AMs。基于这些NGS结果，可以选择合适的靶向治疗，从而提高肺腺癌患者的生存率。这种基于ngs的方法在现实世界的实践中很有用，可以为选择靶向治疗提供指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.