Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Division of Oncology/Hematology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
Cancer Med. 2021 May;10(10):3197-3204. doi: 10.1002/cam4.3874. Epub 2021 May 7.
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.
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.
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).
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.
本研究旨在探讨下一代测序（NGS）在检测肺癌腺癌遗传改变方面的临床应用价值，并分析其对真实世界中肺腺癌治疗的影响。
回顾性分析了 2017 年 3 月至 2018 年 10 月期间接受 NGS 检测的 391 例肺腺癌患者的数据。使用福尔马林固定、石蜡包埋的存档样本进行 NGS 检测，靶向 382 个基因，包括 199 个基因的所有外显子、184 个热点和 8 个经常在癌症中发生重排的部分内含子。对 IV 期疾病进行生存分析。
在 391 例患者中，294 例（75.2%）至少发现了一个可操作的突变。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（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 AM 患者中常见的共突变。在中位随访 16.8 个月时，IV 期疾病患者的中位总生存期为 36.8 个月。根据 NGS 报告接受 AM 相应靶向治疗的患者的生存期明显长于未接受此类治疗的患者（p<0.001）。多因素分析后，针对 AM 的靶向治疗是生存的显著有利因素（无 AM 靶向治疗 vs. 有 AM 靶向治疗，风险比 2.58，95%置信区间 1.57-4.25；p<0.001）。
本研究表明 NGS 可用于检测 AM。基于这些 NGS 结果，可以选择合适的靶向治疗，从而可能改善肺腺癌患者的生存。这种基于 NGS 的方法在真实世界中具有指导意义，可以为选择靶向治疗提供依据。
