晚期非小细胞肺癌的前瞻性一线新一代测序：来自奇里库察肿瘤研究所的真实世界结果
Prospective Upfront Next-Generation Sequencing for Advanced Non-Small Cell Lung Cancer: Real-World Outcomes from the Ion Chiricuță Oncology Institute.
作者信息
Preda Alexandra Cristina, Todor Nicolae, Cârlan Bogdan, Kubelac-Varro Adelina-Dadiana, Iancu Dana Ioana, Mocan Cristina, Vasilica Mariana Bandi, Kubelac Milan-Paul, Vlad Cătălin, Ciuleanu Tudor Eliade
机构信息
Oncology Institute "Prof. Dr. Ion Chiricuță" 34-36 Republicii Street, 400015 Cluj-Napoca, Romania.
Faculty of Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania.
出版信息
Int J Mol Sci. 2025 Apr 5;26(7):3403. doi: 10.3390/ijms26073403.
Upfront Next-Generation Sequencing (NGS) is increasingly recommended in advanced NSCLC to guide targeted therapy. This prospective single-center study in Romania evaluated routine, upfront NGS in advanced NSCLC at baseline (tissue and/or liquid) and progression (liquid). Baseline FoundationOne NGS (tissue/liquid) was performed in 119 consecutive stage IV NSCLC patients, along with PD-L1 immunohistochemistry (IHC, SP263). Liquid biopsy was repeated at progression. Turnaround time (TAT), the prevalence of actionable targets, and clinical utility were assessed. Patients were predominantly male (68.1%) with a median age of 62 years (range 30-86). Most had ECOG PS 0-1 (79%) and non-squamous histology (67.2%). Never-smokers accounted for 25.2%. The median TAT for the NGS results was 9 days (range 5-21). Overall, 671 genetic alterations were detected in 149 genes. The mean number of distinct mutations per patient dropped from 5.6 at baseline to 4.3 at progression. Tissue samples yielded more alterations (6 per patient) than baseline liquid biopsies (4.6). Squamous tumors had more alterations (7.1 vs. 4.8 in non-squamous), and the number of smokers exceeded that of never-smokers (6 vs. 4.5). TP53 was the most frequent (70.59%). Actionable variants were found in 74.8% of patients, though only 35.3% received personalized therapy, largely due to performance status deterioration, reimbursement, or trial availability barriers. Common targets in non-squamous tumors included EGFR (21%), KRAS G12C (11%), NF1 (11%), and ERBB2 (6%); in squamous tumors, common targets included NF1 (24%), PIK3CA (18%), and ERBB2 (8%). Among smokers, driver mutations were often NF1 (15%), PIK3CA (11%), KRAS G12C (9%), and ERBB2 (8%); never-smokers were dominated by EGFR (45%), NF1 (15%), and KRAS G12C (8%). TMB ≥ 10 mut/Mb was seen in 26.9%; no patients were MSI-H. PD-L1 TPS was <1% in 33% of patients, 1-49% in 20%, ≥50% in 18%, and unknown in 29%. Upfront NGS offers rapid, comprehensive genomic data, guiding tailored therapies and trials in advanced NSCLC. Liquid rebiopsy at progression further refines treatment decisions.
在晚期非小细胞肺癌（NSCLC）中，越来越推荐进行一线下一代测序（NGS）以指导靶向治疗。这项在罗马尼亚进行的前瞻性单中心研究评估了晚期NSCLC患者在基线期（组织和/或液体样本）及病情进展期（液体样本）进行常规一线NGS检测的情况。对119例连续的IV期NSCLC患者进行了基线期FoundationOne NGS（组织/液体样本）检测，并同时进行了程序性死亡配体1（PD-L1）免疫组化（IHC，SP263）检测。在病情进展期重复进行液体活检。评估了周转时间（TAT）、可操作靶点的发生率及临床应用价值。患者以男性为主（68.1%），中位年龄为62岁（范围30 - 86岁）。大多数患者东部肿瘤协作组（ECOG）体能状态为0 - 1（79%），组织学类型为非鳞状（67.2%）。从不吸烟者占25.2%。NGS结果的中位TAT为9天（范围5 - 21天）。总体而言，在149个基因中检测到671个基因改变。每位患者不同突变的平均数从基线期的5.6个降至病情进展期的4.3个。组织样本产生的改变更多（每位患者6个），多于基线期液体活检样本（4.6个）。鳞状肿瘤的改变更多（7.1个 vs. 非鳞状肿瘤的4.8个），吸烟者的基因改变数量超过从不吸烟者（6个 vs. 4.5个）。TP53是最常见的（70.59%）。74.8%的患者发现了可操作的变异，但只有35.3%的患者接受了个性化治疗，主要原因是体能状态恶化、报销问题或试验可及性障碍。非鳞状肿瘤的常见靶点包括表皮生长因子受体（EGFR，21%）、KRAS G12C（11%）、神经纤维瘤病1型（NF1，11%）和人表皮生长因子受体2（ERBB2，6%）；在鳞状肿瘤中，常见靶点包括NF1（24%）、磷脂酰肌醇-3-激酶催化亚基α（PIK3CA，18%）和ERBB2（8%）。在吸烟者中，驱动突变通常为NF1（15%）、PIK3CA（11%）、KRAS G12C（9%）和ERBB2（8%）；从不吸烟者中则以EGFR（45%）、NF1（15%）和KRAS G12C（8%）为主。肿瘤突变负荷（TMB）≥10个突变/Mb的患者占26.9%；无患者为微卫星高度不稳定（MSI-H）。33%的患者PD-L1肿瘤比例评分（TPS）<1%，20%的患者为1% - 49%，18%的患者≥50%，29%的患者未知。一线NGS可提供快速、全面的基因组数据，为晚期NSCLC的个体化治疗和临床试验提供指导。病情进展期的液体活检复查可进一步优化治疗决策。
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