Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Cancer Genome Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Cancer Sci. 2024 May;115(5):1656-1664. doi: 10.1111/cas.16130. Epub 2024 Mar 7.
Driver oncogenes are investigated upfront at diagnosis using multi-CDx systems with next-generation sequencing techniques or multiplex reverse-transcriptase polymerase chain reaction assays. Additionally, from 2019, comprehensive genomic profiling (CGP) assays have been available in Japan for patients with advanced solid tumors who had completed or were expected to complete standard chemotherapy. These assays are expected to comprehensively detect the driver oncogenes, especially for patients with non-small cell lung cancer (NSCLC). However, there are no reports of nationwide research on the detection of driver oncogenes in patients with advanced NSCLC who undergo CGP assays, especially in those with undetected driver oncogenes at diagnosis. In this study, we investigated the proportion of driver oncogenes detected in patients with advanced NSCLC with undetectable driver oncogenes at initial diagnosis and in all patients with advanced NSCLC who underwent CGP assays. We retrospectively analyzed data from 986 patients with advanced NSCLC who underwent CGP assays between August 2019 and March 2022, using the Center for Cancer Genomics and Advanced Therapeutics database. The proportion of driver oncogenes newly detected in patients with NSCLC who tested negative for driver oncogenes at diagnosis and in all patients with NSCLC were investigated. Driver oncogenes were detected in 451 patients (45.7%). EGFR was the most common (16.5%), followed by KRAS (14.5%). Among the 330 patients with undetected EGFR, ALK, ROS1, and BRAF V600E mutations at diagnosis, 81 patients (24.5%) had newly identified driver oncogenes. CGP assays could be useful to identify driver oncogenes in patients with advanced NSCLC, including those initially undetected, facilitating personalized treatment.
在诊断时,使用下一代测序技术或多重逆转录酶聚合酶链反应检测的多 CDx 系统会对驱动基因进行初步检测。此外,自 2019 年以来,综合基因组分析(CGP)检测已在日本用于晚期实体瘤患者,这些患者已完成或预计完成标准化疗。这些检测有望全面检测驱动基因,特别是对非小细胞肺癌(NSCLC)患者。然而,目前还没有关于在接受 CGP 检测的晚期 NSCLC 患者中检测驱动基因的全国性研究报告,特别是在初始诊断时未检测到驱动基因的患者中。在这项研究中,我们调查了在初始诊断时未检测到驱动基因的晚期 NSCLC 患者和所有接受 CGP 检测的晚期 NSCLC 患者中检测到的驱动基因的比例。我们使用癌症基因组中心和先进治疗数据库,对 2019 年 8 月至 2022 年 3 月间接受 CGP 检测的 986 例晚期 NSCLC 患者的数据进行了回顾性分析。我们研究了在初始诊断时检测到的驱动基因呈阴性的 NSCLC 患者和所有 NSCLC 患者中检测到的新的驱动基因的比例。在 451 例(45.7%)患者中检测到了驱动基因。EGFR 是最常见的(16.5%),其次是 KRAS(14.5%)。在 330 例初始诊断时未检测到 EGFR、ALK、ROS1 和 BRAF V600E 突变的患者中,有 81 例(24.5%)新发现了驱动基因。CGP 检测对于识别包括初始未检测到的驱动基因在内的晚期 NSCLC 患者的驱动基因可能很有用,从而促进个体化治疗。