Xu Qingsheng, Huang Kaiyuan, Tong Luqing, Yan Danfang, Zhao Yilei, Yang Hanjin, Jin Weili, Zhang Luyuan, Cai Jinquan, Chen Qun
Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
BMC Med. 2025 May 28;23(1):301. doi: 10.1186/s12916-025-04134-7.
The treatments for refractory leptomeningeal metastasis (RLM) of non-small cell lung cancer (NSCLC) are limited, and response assessment is complex and challenging. This clinical trial aimed to evaluate the efficacy of intrathecal pemetrexed (IP) and response assessment using cerebrospinal fluid (CSF) tumor marker in RLM.
This was a single-center, single-arm, phase II adaptive clinical trial. Patients with RLM of NSCLC were eligible for inclusion. Patients were assigned to receive 30 mg of IP every 3 weeks for a total of 6 cycles. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS) evaluated according to EANO-ESMO response assessment, disease control rate, the concordance of CSF tumor marker response with EANO-ESMO response assessment, and safety.
A total of 29 patients were enrolled in the trial. The median PFS was 10.03 months (95% CI, 6.42-13.64), and the median OS was 20.37 months (95% CI, 14.86-25.88), respectively. A ± 35% threshold for CSF tumor marker level change (TML) yielded the optimal predictive performance, with AUCs of 0.890 (95% CI, 0.833-0.947), 0.911 (95% CI, 0.870-0.951), and 0.784 (95% CI, 0.717-0.850) for EANO-ESMO response, progression, and stable, respectively. Most patients (93.1%) experienced grade 1-2 treatment-related adverse events.
Our therapeutic regimen of IP provided a practical, survival-extending, and tolerant option for RLM patients. CSF tumor marker response was correlated with EANO-ESMO response assessment, offering an effective tool for response monitoring of RLM.
Chinese Clinical Trial Register (ChiCTR) ChiCTR2200057235. Registered on March 1, 2022. Date of the first patient enrollment: April 29, 2022.
非小细胞肺癌（NSCLC）难治性软脑膜转移（RLM）的治疗方法有限，反应评估复杂且具有挑战性。本临床试验旨在评估鞘内注射培美曲塞（IP）的疗效以及使用脑脊液（CSF）肿瘤标志物对RLM进行反应评估。
这是一项单中心、单臂、II期适应性临床试验。符合条件的纳入NSCLC的RLM患者。患者被分配接受每3周30mg的IP，共6个周期。主要终点是总生存期（OS）。次要终点包括根据欧洲神经肿瘤协会（EANO）-欧洲肿瘤内科学会（ESMO）反应评估标准评估的无进展生存期（PFS）、疾病控制率、CSF肿瘤标志物反应与EANO-ESMO反应评估的一致性以及安全性。
共有29例患者入组该试验。中位PFS为10.03个月（95%CI，6.42-13.64），中位OS为20.37个月（95%CI，14.86-25.88）。CSF肿瘤标志物水平变化（TML）±35%的阈值产生了最佳预测性能，EANO-ESMO反应、进展和稳定的曲线下面积（AUC）分别为0.890（95%CI，0.833-0.947）、0.911（95%CI，0.870-0.951）和0.784（95%CI，0.717-0.850）。大多数患者（93.1%）经历了1-2级治疗相关不良事件。
我们的IP治疗方案为RLM患者提供了一种实用、延长生存期且耐受性良好的选择。CSF肿瘤标志物反应与EANO-ESMO反应评估相关，为RLM反应监测提供了一种有效工具。
中国临床试验注册中心（ChiCTR）ChiCTR2200057235。于2022年3月1日注册。首例患者入组日期：2022年4月29日。
