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背景与目的 软脑膜转移（leptomeningeal metastasis, LM）在晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者中的发病率逐年上升，但其治疗手段有限，预后较差。鞘内注射培美曲塞（intrathecal Pemetrexed, IP）在LM治疗领域具有广泛的应用前景。本研究旨在评估IP在表皮生长因子受体（epidermal growth factor receptor, EGFR）突变阳性NSCLC-LM患者中的疗效、安全性及最佳联合应用模式，以期为此类患者探寻更精准的个体化治疗策略提供真实世界数据支持。方法 回顾性收集2018年1月至2024年6月在南京大学医学院附属鼓楼医院接受IP治疗的104例EGFR突变阳性NSCLC-LM患者的临床资料、治疗方案和生存数据。系统分析入组患者的总生存期（overall survival, OS）、无进展生存期（progression-free survival, PFS）、临床有效率和不良反应（adverse events, AEs）。结果 104例EGFR突变阳性NSCLC-LM患者的中位PFS为9.6个月，中位OS为13.0个月，6个月和1年OS率分别为80.8%和56.5%，临床有效率为77.9%。常见的AEs是骨髓抑制（58.7%）和转氨酶升高（25.0%）。9例（8.7%）患者出现4级骨髓抑制，给予对症治疗后恢复正常。亚组分析显示，卡氏体能状态（Karnofsky performance status, KPS）评分≥60分的患者OS显著长于KPS<60分患者（14.4 vs 9.0个月，P=0.0022）。规律接受贝伐珠单抗治疗的LM患者中位OS明显高于未接受贝伐珠单抗治疗者（19.2 vs 10.5个月，P=0.0011）。结论 IP治疗在EGFR突变阳性NSCLC-LM患者中具有良好的疗效和安全性，联合贝伐珠单抗可发挥协同抗肿瘤作用，进一步改善预后。
Background and objective The incidence of leptomeningeal metastasis (LM) in patients with advanced non-small cell lung cancer (NSCLC) is increasing gradually. However, it poses therapeutic challenges due to limited effective interventions. Intrathecal Pemetrexed (IP) holds broad application prospects in the therapeutic domain of LM. This study aims to evaluate the efficacy, safety, and optimal combination strategies of IP in NSCLC-LM patients with epidermal growth factor receptor (EGFR) mutation-positive status, with the aim of providing real-world data support for exploring more precise personalized treatment strategies for these patients. Methods 104 EGFR-mutated NSCLC-LM patients who received IP treatment at Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School from January 2018 to June 2024 were analyzed retrospectively. Clinical parameters, treatment regimens, and survival outcomes were collected. The overall survival (OS), progression-free survival (PFS), clinical response rate and adverse events (AEs) were evaluated. Results The cohort demonstrated a median PFS of 9.6 months and OS of 13.0 months with 6-month and 1-year OS rates of 80.8% and 56.5%, respectively. Clinical response was observed in 77.9% of patients. The common AEs were myelosuppression (58.7%) and elevation of hepatic aminotransferases (25.0%). Nine (8.7%) patients experienced grade 4 myelosuppression and recovered to normal after receiving symptomatic treatment. Subgroup analyses revealed prolonged OS in patients with Karnofsky performance status (KPS) ≥60 versus <60 (14.4 vs 9.0 months, P=0.0022) and those receiving Bevacizumab therapy versus not (19.2 vs 10.5 months, P=0.0011). Conclusion IP exhibits promising efficacy and manageable toxicity in EGFR-mutated NSCLC-LM patients. When combined with Bevacizumab, it exerts synergistic antitumor effects with the potential to further improve clinical outcomes.