de Luca Caterina, Russo Gianluca, Nacchio Mariantonia, Ingenito Maria, Palumbo Lucia, Gragnano Gianluca, Conticelli Floriana, Russo Maria, Rocco Danilo, Gridelli Cesare, Bianco Roberto, Galetta Domenico, Troncone Giancarlo, Parente Paola, Iaccarino Antonino
Department of Public Health, Federico II University of Naples, Via S. Pansini, 5, 80131, Naples, Italy.
Pneumo-Oncology Unit, Ospedali dei Colli Monaldi Cotugno CTO, Napoli, Italy.
J Liq Biopsy. 2023 Nov 17;2:100128. doi: 10.1016/j.jlb.2023.100128. eCollection 2023 Dec.
Lung cancer is the leading cause of cancer death worldwide. Over the last decade, molecular testing of a growing number of predictive biomarkers has become mandatory in the management of NSCLC patients. However, a major obstacle in routine clinical practice is the scant quantity of available tissue specimens obtainable from advanced stage of NSCLC patients. Thus, liquid biopsy, mostly involving blood sampling, has now been integrated in routine diagnostic practice. However, although liquid biopsies constitute a versatile, compliant, and dynamic source of nucleic acids, many of the current testing approaches pose few technical challenges. Here, to validate the feasibility of implementing NGS-based liquid biopsy approaches in routine diagnostic practice, we overviewed the NGS molecular data generated by our in-house narrow gene panel on plasma samples from real-world NSCLC patients.
Our Institution received testing request on liquid biopsy samples from peripheral institutions not equipped to internally analyze liquid biopsy samples. Molecular data from NSCLC patients following oncological requested for clinically approved plasma-based biomarkers evaluated in a diagnostic routine setting from January 2020 to September 2022 were retrieved from our institutional archive. A customized NGS panel integrated with an optimized bioinformatic pipeline was adopted.
Overall, a total of n = 185 cases were retrieved. Of note, 103 (55.7 %) and 82 (44.3 %) patients were analyzed at basal setting and after resistance to first line TKI administration, respectively. Moreover, 31 out of 185 (16.7 %) cases reveled clinically relevant alterations. In particular, 6 out of 31 (19.3 %) and 25 out 31 (80.7 %) mutated patients were tested in basal setting and after first or second line TKIs progression. In addition, exon 20 p.T790 M mutation was also detected in 12 out of 25 (48.0 %) concomitant mutated cases. Moreover, hot spot mutations were found in 24 out of 185 (13.0 %) cases. Among them, exon 2 p.G12C clinically relevant mutations were observed in 8 out 24 cases (33.3 %).
This review highlights the technical suitability of an NGS-based liquid biopsy system for the analysis of clinically relevant mutations in NSCLC patients.
肺癌是全球癌症死亡的主要原因。在过去十年中，对越来越多的预测性生物标志物进行分子检测已成为非小细胞肺癌（NSCLC）患者管理中的强制性要求。然而，常规临床实践中的一个主要障碍是，从晚期NSCLC患者身上获取的可用组织标本数量稀少。因此，主要涉及血液采样的液体活检现已纳入常规诊断实践。然而，尽管液体活检构成了一种通用、合规且动态的核酸来源，但目前许多检测方法几乎没有技术挑战。在此，为了验证在常规诊断实践中实施基于二代测序（NGS）的液体活检方法的可行性，我们概述了我们内部针对来自真实世界NSCLC患者血浆样本的窄基因panel所产生的NGS分子数据。
我们机构收到了来自周边机构的液体活检样本检测请求，这些机构没有内部分析液体活检样本的能力。从我们的机构档案中检索了2020年1月至2022年9月在诊断常规环境中对经临床批准的基于血浆的生物标志物进行肿瘤学检测的NSCLC患者的分子数据。采用了一个定制的NGS panel，并结合了优化的生物信息学流程。
总体而言，共检索到n = 185例病例。值得注意的是，分别在基线状态和对一线酪氨酸激酶抑制剂（TKI）治疗耐药后对103例（55.7%）和82例（44.3%）患者进行了分析。此外，185例中的31例（16.7%）病例显示出临床相关改变。特别是，31例突变患者中的6例（19.3%）和25例（80.7%）分别在基线状态以及一线或二线TKI进展后进行了检测。此外，在25例伴随突变的病例中，有12例（48.0%）还检测到外显子20 p.T790M突变。此外，在185例中的24例（13.0%）病例中发现了热点突变。其中，24例中的8例（33.3%）观察到外显子2 p.G12C临床相关突变。
本综述强调了基于NGS的液体活检系统在分析NSCLC患者临床相关突变方面的技术适用性。
