表皮生长因子受体突变阳性 (EGFRm) NSCLC 软脑膜转移 (LM) 的诊断和治疗具有挑战性。我们的目的是确定脑脊液 (CSF) 和血浆中对奥希替尼的耐药机制 (RM)。纳入奥希替尼治疗期间出现新发或进展性 LM 的 EGFRm 患者。 NGS Ampliseq 对从 CSF 中分离的 DNA 进行分析。腰椎穿刺后，患者接受奥希替尼剂量递增（DE，每日 160 毫克）。奥希替尼 DE 治疗后 4 周评估临床和放射学反应。纳入了 28 名患者。 93% 的 CSF 样本 (n=26) 中发现了驱动突变。七人 (27%) 携带 ≥1 RM。 25 名患者 (89%) 接受了奥希替尼 DE 治疗。四个星期后，五名患者的症状有所改善，九名患者的症状稳定，十一名患者的症状恶化。二十一名 (84%) 患者接受了 MR 成像。 4 例显示放射学改善，14 例稳定，3 例恶化。27% 的患者在脑脊液 ctDNA 中发现 RM，在撰写本文时，这些都不是可靶向的，奥希替尼 DE 的临床疗效似乎有限。 EGFRm NSCLC LM 的诊断和治疗策略有很多收获。© 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

Diagnosis and treatment of leptomeningeal metastases (LM) in epidermal growth factor receptor mutation positive (EGFRm+) NSCLC is challenging. We aimed to identify resistance mechanisms (RM) to osimertinib in cerebrospinal fluid (CSF) and plasma.EGFRm+ patients with new or progressive LM during osimertinib were enrolled. NGS Ampliseq was performed on DNA isolated from CSF. Patients were prescribed osimertinib dose escalation (DE, 160mg QD) following lumbar puncture. Clinical and radiological response was evaluated four weeks after osimertinib DE.Twenty-eight patients were included. The driver mutation was identified in 93% of CSF samples (n=26). Seven (27%) harbored ≥1 RM. Twenty-five patients (89%) were prescribed osimertinib DE. Four weeks afterwards, symptoms improved in five patients, stabilized in nine and worsened in eleven patients. Twenty-one (84%) patients underwent MR imaging. Four showed radiological improvement, fourteen stabilization, and three worsening.In 27% of patients an RM was found in CSF ctDNA, none of which are targetable at time of writing, and clinical efficacy of osimertinib DE seems limited. There is much to gain in diagnostic as well as therapeutic strategies in EGFRm+ NSCLC LM.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.