液体活检通过单重测试检测无 EGFR 突变的 NSCLC 中的基因组驱动因素：WJOG13620L。
Liquid biopsy detects genomic drivers in NSCLC without EGFR mutations by single-plex testing: WJOG13620L.
发表日期：2023 Nov 10
作者：
Takehiro Uemura, Hirotsugu Kenmotsu, Daisuke Hazama, Shunsuke Teraoka, Hiroshi Kobe, Koichi Azuma, Teppei Yamaguchi, Takeshi Masuda, Toshihide Yokoyama, Kohei Otsubo, Koji Haratani, Daisuke Hayakawa, Masahide Oki, Shinnosuke Takemoto, Tomohiro Ozaki, Yusaku Akashi, Akito Hata, Hiroya Hashimoto, Nobuyuki Yamamoto, Kazuhiko Nakagawa
来源：
GENES & DEVELOPMENT
摘要：
近 70% 的日本晚期非鳞状非小细胞肺癌 (NSCLC) 患者发生可操作的肿瘤基因组改变，主要是 EGFR 突变。肿瘤组织的标准评估包括快速检测 EGFR 突变、ALK 融合和 ROS1 融合。我们对 EGFR 检测后无驱动改变的患者进行了一项前瞻性观察性研究 (WJOG13620L)，对循环肿瘤 DNA (ctDNA) 进行后续下一代测序。未经治疗的无 EGFR 突变的晚期（IIIB-IV 期或复发）非鳞状 NSCLC 患者根据肿瘤组织的单重检测，被纳入本研究。具有其他已知驱动突变或接受全面基因组分析的患者被排除在外。通过Guardant360对血浆进行分析，主要终点是九个基因中至少一个基因发生致病性基因改变的患者比例。在入组的72名患者中，检测到ALK和ROS1融合的比例分别为86.1%和65.2%。 21 名患者检测到预定义基因的改变（29.2%；95% 置信区间：19.0-41.1，p < 0.001 [单边原假设比例为 10%]），包括 RET 融合 (n = 1) 和突变KRAS (n = 11)、EGFR (n = 5)、ERBB2 (n = 3) 和 BRAF (n = 1)。从样本提交到结果的中位时间为 8 天（范围为 5-17 天）。对于晚期非鳞状 NSCLC 患者，如果单次检测后未检测到任何变化，则应在一线治疗前考虑进行快速后续 ctDNA 综合检测。丛组织测试。© 2023 作者。约翰·威利出版的癌症医学
Actionable tumor genomic alterations, primarily EGFR mutations, occur in nearly 70% of Japanese advanced nonsquamous non-small cell lung cancer (NSCLC) patients. Standard assessment of tumor tissue includes rapid testing for EGFR mutations, ALK fusions and ROS1 fusions. We conducted a prospective observational study (WJOG13620L) of follow-on next-generation sequencing of circulating tumor DNA (ctDNA) in patients without driver alterations after EGFR testing.Patients with untreated advanced (Stage IIIB-IV or relapsed) nonsquamous NSCLC without EGFR mutations according to single-plex testing of tumor tissue, were enrolled into this study. Patients with other known driver mutations or who underwent comprehensive genomic profiling were excluded. Plasma was analyzed by Guardant360, and the primary endpoint was the proportion of patients with pathogenic gene alterations in at least one of nine genes.Among the 72 patients enrolled, ALK and ROS1 fusions were tested in 86.1% and 65.2%, respectively. Alterations in pre-defined genes were detected in 21 patients (29.2%; 95% confidence interval: 19.0-41.1, p < 0.001 [one-sided null hypothesis proportion of 10%]), including RET fusion (n = 1) and mutations in KRAS (n = 11), EGFR (n = 5), ERBB2 (n = 3), and BRAF (n = 1). Median time from sample submission to results was 8 days (range, 5-17 days).Rapid follow-on comprehensive testing of ctDNA should be considered prior to first-line treatment for patients with advanced nonsquamous NSCLC when no alterations are detected after single-plex tissue testing.© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.