确定晚期癌症最合适的靶向疗法具有挑战性。我们利用全面的下一代测序 (NGS) 检测对转移性实体瘤进行了分子分析，以确定基因组改变的类型、频率、可操作性以及与 PD-L1 表达的潜在相关性。总共 304 名接受过严格预处理的转移性实体瘤成年患者招募了 2019 年 1 月至 2021 年 3 月期间接受治疗的癌症。 CLIA/UKAS 认可的 Oncofocus 检测针对 505 个基因，用于新获得或存档的活检组织。在适当的情况下使用卡方、Kruskal-Wallis 和 Wilcoxon 秩和检验。结果显着，P < .05。总共 237 个肿瘤 (78%) 存在潜在的可操作基因组改变。 68.9% 的肿瘤病例中 PD-L1 呈阳性。突变基因/肿瘤的中位数为 2.0 (IQR: 1.0-3.0)。只有 34.5% 的 ESCAT Tier I-II 可采取行动，并且根据癌症类型的患病率不同。 DNA 损伤修复 (14%)、PI3K/AKT/mTOR (14%) 和 RAS/RAF/MAPK (12%) 通路是最常改变的。 PD-L1、ESCAT、年龄、性别和肿瘤突变状态之间没有发现关联。总体而言，62 名患者接受了针对性治疗，其中 37.1% 获得客观缓解。针对不同癌症类型的相同分子驱动治疗可能会产生相反的临床结果。我们强调使用基于 NGS 的全面面板进行转移性实体瘤分子分析的临床价值，以改进不确定情况下的治疗算法并促进临床试验招募。然而，以肿瘤类型特异性方式解释基因组改变至关重要。© 作者 2024。由牛津大学出版社出版。

The identification of the most appropriate targeted therapies for advanced cancers is challenging. We performed a molecular profiling of metastatic solid tumors utilizing a comprehensive next-generation sequencing (NGS) assay to determine genomic alterations' type, frequency, actionability, and potential correlations with PD-L1 expression.A total of 304 adult patients with heavily pretreated metastatic cancers treated between January 2019 and March 2021 were recruited. The CLIA-/UKAS-accredit Oncofocus assay targeting 505 genes was used on newly obtained or archived biopsies. Chi-square, Kruskal-Wallis, and Wilcoxon rank-sum tests were used where appropriate. Results were significant for P < .05.A total of 237 tumors (78%) harbored potentially actionable genomic alterations. Tumors were positive for PD-L1 in 68.9% of cases. The median number of mutant genes/tumor was 2.0 (IQR: 1.0-3.0). Only 34.5% were actionable ESCAT Tier I-II with different prevalence according to cancer type. The DNA damage repair (14%), the PI3K/AKT/mTOR (14%), and the RAS/RAF/MAPK (12%) pathways were the most frequently altered. No association was found among PD-L1, ESCAT, age, sex, and tumor mutational status. Overall, 62 patients underwent targeted treatment, with 37.1% obtaining objective responses. The same molecular-driven treatment for different cancer types could be associated with opposite clinical outcomes.We highlight the clinical value of molecular profiling in metastatic solid tumors using comprehensive NGS-based panels to improve treatment algorithms in situations of uncertainty and facilitate clinical trial recruitment. However, interpreting genomic alterations in a tumor type-specific manner is critical.© The Author(s) 2024. Published by Oxford University Press.