液体活检结合下一代测序（NGS）已成为肿瘤突变谱定的一种有前景的工具。本研究描述了以基于血液的全面基因谱（CGP）为基础对意大利肺癌患者进行基因组分析，以评估基因组景观的复杂性及其对患者治疗选择的增强作用。2021年1月至2021年12月，共有229名肺癌患者通过FoundationOne®Liquid CDx（F1LCDx®）测试了循环肿瘤DNA（ctDNA）。F1LCDx®报告涉及324个与癌症相关的基因和基因组标记，包括肿瘤分数（TF）和基于血液的肿瘤突变负荷（bTMB）。根据ESMO分子靶点临床行动性评分（ESCAT），检测到的变异被分类。90.4%的患者血浆中至少有一种可检测的变异。最常见的突变基因是TP53（47.6%）、DNMT3A（33.2%）、EGFR（20.1%）和KRAS（15.7%）。检测到18.3%的患者存在升高的TF，表明测试结果具有较高的可靠性。根据ESCAT分类，27.1%的样本中检测到可能可行的变异（I-II级）。另外，5.2%的样本中存在适用于其他癌症类型的已批准药物的变异（III级）。此外，13.1%的肿瘤表现出较高的bTMB，可能预测对免疫疗法的响应。总体而言，有156名（68.1%）患者符合临床试验的入组条件。液体活检NGS是一种可行且有价值的指导个体化治疗方法。采用基于血液的CGP可能有助于识别更多可行的突变，并增加入组临床试验的机会。 版权所有©2023 Elsevier B.V。保留所有权利。

Liquid biopsy with next-generation sequencing (NGS) has emerged as a promising tool for tumor mutation profiling. In this study, we describe the genomic profile of Italian lung cancer patients tested with blood-based comprehensive genomic profiling (CGP) to assess the genomic landscape complexity and its impact on enhancing treatment options for patients.Between January 2021 and December 2021, a total of 229 lung cancer patients were profiled by FoundationOne®Liquid CDx (F1LCDx®) assay on circulating tumor DNA (ctDNA). F1LCDx® reports alterations across 324 cancer-related genes and genomic signatures, including tumor fraction (TF) and blood-based tumor mutational burden (bTMB). Detected variants were classified according to the ESMO Scale of Clinical Actionability for molecular Targets (ESCAT).90.4% of patients had at least one detectable alteration in plasma. The most frequently mutated genes were TP53 (47.6%), DNMT3A (33.2%), EGFR (20.1%), and KRAS (15.7%). Elevated TF was detected in 18.3% of patients, suggesting high reliability of test results. According to the ESCAT classification, potentially actionable alterations (Tier I-II) were identified in 27.1% of samples. An additional 5.2% harbored an alteration for which an approved drug is available in other cancer types (Tier III). Furthermore, 13.1% of tumors exhibited high bTMB, which may predict response to immunotherapy. Overall, 156 (68.1%) patients were eligible for enrolment in clinical trials.Liquid biopsy NGS is a viable and valuable approach to guide personalized therapy. The use of blood-based CGP may help identify a larger number of actionable mutations and increase chances of enrolment in clinical trials.Copyright © 2023 Elsevier B.V. All rights reserved.