Does large NGS panel analysed using exome tumour sequencing improve the management of advanced non-small-cell lung cancers?
Does large NGS panel analysed using exome tumour sequencing improve the management of advanced non-small-cell lung cancers?
复制标题
DOI：
10.1016/j.lungcan.2021.08.013
复制
发表时间：
2021-08
期刊：
影响因子：
5.3
通讯作者：
Julie Niogret;Lorraine Dalens;C. Truntzer;Sandy Chevrier;L. Favier;A. Lagrange;B. Coudert;Cléa Fraisse;P. Foucher;A. Zouak;V. Westeel;V. Goussot;V. Derangère;J. Albuisson;L. Arnould;R. Boidot;C. Kaderbhai;F. Ghiringhelli
中科院分区：
文献类型：
--
作者：
Julie Niogret;Lorraine Dalens;C. Truntzer;Sandy Chevrier;L. Favier;A. Lagrange;B. Coudert;Cléa Fraisse;P. Foucher;A. Zouak;V. Westeel;V. Goussot;V. Derangère;J. Albuisson;L. Arnould;R. Boidot;C. Kaderbhai;F. Ghiringhelli
简介非小细胞肺癌（NSCLC）是最常见和致命的癌症之一。现在已知致癌基因成瘾的几种分子驱动因素是靶向治疗的强有力的预测生物标志物。大型下一代测序（LNGS）的进步提高了检测潜在可靶向突变的能力。然而，以个体化方式将 LNGS 纳入临床管理仍然具有挑战性。方法在这项单中心观察性研究中，我们纳入了所有接受 LNGS 的晚期 NSCLC 患者。对 323 个癌症相关基因进行了体细胞和种系外显子组分析。对变异进行分类，分子肿瘤委员会 (MTB) 提出治疗建议。结果我们在 2015 年 3 月至 2018 年 1 月期间对 281 名晚期 NSCLC 患者进行了 LNGS 分析。只有 3% 的病例发生技术故障。检测到三百五十六个可靶向突变。在 209 名患者中至少发现了一种靶向突变。对于所有这些患者，MTB 能够根据肿瘤遗传谱和治疗史的评估推荐靶向药物治疗。 29 名患者 (13.9%) 随后接受了 MTB 推荐的靶向治疗。我们没有观察到这些患者的临床获益有任何改善。结论在本病例系列中，我们表明将 LNGS 纳入常规临床管理是可行的，但似乎无法为晚期 NSCLC 患者的治疗提供临床获益。
IntroductionNon-small-cell lung cancer (NSCLC) is one of the most common and deadly cancers. Several molecular drivers of oncogene addiction are now known to be strong predictive biomarkers for target therapies. Advances in large Next Generation Sequencing (LNGS) have improved the ability to detect potentially targetable mutations. However, the integration of LNGS into clinical management in an individualized manner remains challenging.MethodsIn this single-center observational study we included all patients with advanced NSCLC who underwent LNGS. Somatic and germline exome analysis was performed with a restriction on 323 cancer related genes. Variants were classified and Molecular Tumour Board (MTB) made therapeutic propositions.ResultsWe performed LNGS analysis in 281 patients with advanced NSCLC between March 2015 and January 2018. Technical failure occurred in only 3% of cases. Three hundred and fifty-six targetable mutations were detected. At least one targetable mutation was found in 209 patients. For all these patients, the MTB was able to recommend treatment with a targeted agent based on the evaluation of the tumour’s genetic profile and treatment history. Twenty-nine patients (13.9%) were subsequently treated with an MTB-recommended targeted therapy. We did not observe any improvement in terms of clinical benefit for these patients.ConclusionsIn this case series, we show that including LNGS into routine clinical management was feasible but does not appear to provide clinical benefit in the management of patients with advanced NSCLC.