经Ommaya囊侧脑室注射培美曲塞治疗非小细胞肺癌伴软脑膜转移的疗效及其影响因素  

Efficacy and influencing factors on intrathecal chemotherapy with pemetrexed via the Ommaya reservoir for leptomeningeal carcinomatosis from non-small cell lung cancer

作　　者：谢雨文 徐婷 程弯弯 沈华 方申存 XIE Yuwen;XU Ting;CHENG Wanwan;SHEN Hua;FANG Shencun(Department of Respiratory Medicine,Nanjing Chest Hospital,Affiliated Brain Hospital of Nanjing MedicalUniversity,Nanjing210029,China;Department of Oncology,Affiliated Hospital of Yifu,Nanjing Medical University,Nanjing211112,China)

机构地区：[1]南京医科大学附属脑科医院(南京市胸科医院)呼吸内科,江苏南京210029 [2]南京医科大学附属逸夫医院肿瘤内科,江苏南京211112

出　　处：《中华肿瘤防治杂志》2023年第17期1034-1039,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81874230);江苏省“六个一工程”拔尖人才科研项目(LYG2019006)。

摘　　要：目的探索经Ommaya囊侧脑室内注射培美曲塞治疗非小细胞肺癌(NSCLC)伴软脑膜转移(LM)的疗效和安全性。方法回顾性分析南京医科大学附属脑科医院2021-08-01-2022-12-31收治的45例NSCLC伴LM患者的临床资料。患者男18例,女27例;年龄37~74岁,中位年龄55岁。所有患者均接受通过Ommaya囊向侧脑室内注射培美曲塞,根据头颅增强MRI、神经症状或体征的改善以及卡氏功能状态(KPS)评分的变化等来评估治疗效果,根据常见不良事件评价标准(CTCAE)4.0版评估不良反应。生存分析采用Kaplan-Meier法并行log-rank检验,Cox回归分析预后相关的预测因素。结果头颅增强MRI显示,好转15例(33.3%),稳定28例(62.2%),进展2例(4.4%)。培美曲塞累积量达到120、180和240 mg时,癌胚抗原的下降率分别为(47.9±30.8)%、(64.2±32.5)%和(74.2±34.3)%。侧脑室化疗总有效率为75.6%(34/45),中位颅内无进展生存期(iPFS)为6.5个月。50和30 mg培美曲塞组的中位iPFS分别为12.4和6.0个月(HR=4.360,95%CI:1.95~22.85,P=0.037)。单因素生存分析显示,KPS评分、治疗线数、脑转移和培美曲塞的剂量对iPFS影响的差异有统计学意义,均P<0.05。多因素分析显示,KPS评分>30分和培美曲塞的剂量为50 mg是iPFS的不良预后因素。脑室内注射培美曲塞常见的不良反应是骨髓抑制和无菌性脑膜炎。结论经Ommaya囊侧脑室内注射培美曲塞治疗NSCLC伴LM可以同时改善患者生活质量和延长生存时间,是一种安全有效的治疗措施。Objective To explore the efficacy and safety of intrathecal chemotherapy with pemetrexed via the Ommaya reservoir for leptomeningeal metastasis(LM)from non-small cell lung cancer(NSCLC).Methods Retrospective analyses were performed on NSCLC patients with LM at the Affiliated Brain Hospital of Nanjing Medical University from August 1,2021to December 31,2022.Among the 45patients,there were 18male and 27female patients,and the median age was 55years(ranging between 37and 74years).All patients received intrathecal chemotherapy with pemetrexed via the Ommaya reservoir.The therapeutic effect was evaluated according to cranial enhanced magnetic resonance imaging(MRI),the improvement of neurological symptoms or signs,and changes in Karnofsky Performance Status(KPS)scores.The adverse reactions were evaluated based on the Common Adverse Event Evaluation Criteria(CTCAE)version 4.0.Kaplan-Meier was used for survival analysis,and log-rank test was conducted.Prognostic factors were predicted by multivariate Cox regression analyses.Results Enhanced MRI scan results showed that 15(33.3%)cases were improved,28(62.2%)cases were stable,and 2(4.4%)cases were progressed.The CEA decline rate were(47.9±30.8)%,(64.2±32.5)%and(74.2±34.3)%,when the accumulated dose of pemetrexed exceeded 120mg,180mg,and 240mg,respectively.The total effective rate of intrathecal chemotherapy was 75.6%(34/45).The median intracranial progression free survival(iPFS)was 6.5months.The median iPFS were 12.4months and 6.0months(HR=4.360,95%CI:1.95-22.85,P=0.037)for the 50mg and 30mg pemetrexed groups,respectively.Univariate survival analysis showed that KPS score,number of prior lines of therapy,brain parenchymal metastasis,and pemetrexed had statistically significant effects on iPFS(all P<0.05).Multivariate analysis showed that KPS score of>30and 50mg pemetrexed were the independent risk factors of iPFS.The common adverse reactions were myelosuppression and aseptic meningitis.Conclusion Intrathecal chemotherapy with pemetrexed in NSCLC patients with LM can im

关 键 词：非小细胞肺癌 软脑膜转移 OMMAYA囊 侧脑室化疗 培美曲塞 

分 类 号：R734.2[医药卫生—肿瘤]