甲氨蝶呤鞘内注射化疗对肺癌脑膜转移的疗效分析

Analysis of the efficacy of intrathecal methotrexate for leptomeningeal metastases from lung cancer

目的探讨鞘内注射甲氨蝶呤(MTX)治疗肺癌脑膜转移患者的临床疗效和预后影响因素。方法收集108例接受MTX鞘内注射化疗的肺癌脑膜转移患者的临床资料,分析MTX鞘内注射化疗的症状改善情况、脑脊液生化水平和总生存时间(OS),肺癌脑膜转移患者预后的影响因素采用COX风险比例模型。结果 108例肺癌脑膜转移患者中位OS为14个月。鞘内注射化疗后56例患者神经系统症状好转。与鞘内注射化疗前脑脊液生化水平比较,脑脊液蛋白含量降低,脑脊液葡萄糖含量升高,差异均有统计学意义(P<0.05)。COX多因素分析显示,卡式功能状态(KPS)评分≥60分、接受EGFR-TKI治疗是腰椎穿刺MTX鞘内注射化疗肺癌脑膜转移患者预后良好的独立保护因素,合并脑实质转移是其预后不良的独立危险因素。结论腰椎穿刺MTX鞘内注射化疗可改善患者临床症状,治疗安全有效。KPS评分≥60分、无脑实质转移的肺癌脑膜转移患者生存时间较长,联合应用EGFR-TKI治疗可改善接受MTX鞘内注射化疗的肺癌脑膜转移患者预后。

Objective To investigate the clinical efficacy, safety and factors influencing the prognosis of intrathecal methotrexate (MTX) for the treatment of leptomeningeal metastases from lung cancer. Method We retrospectively evaluated the clinical and pathological data of 108 patients who underwent intrathecal chemotherapy with MTX after a diagnosis of leptomeningeal metastases from lung cancer. The clinical efficacy, cerebrospinal fluid contents, adverse reactions and survival time in these patients were analyzed, besides, the prognostic factors were investigated using COX proportional hazard model. Result The median overall survival (OS) time in the 108 patients was 14 months. After intrathecal chemotherapy, the nervous system symptoms were improved in 56 patients. As to the change of cerebrospinal fluid content, cerebrospinal fluid protein decreased while cerebrospinal fluid glucose increased significantly after intrathecal MTX, the differences were of statistical significance (P<0.05). COX multivariate analysis showed that, Karnofsky performance score (KPS)≥60, and receiving EGFR-TKI treatment were independent prognostic factors for patients with leptomeningeal metastases from lung cancer receiving intrathecal MTX, while the comorbidity of parenchymal metastases was a risk factor. Conclusion Intrathecal MTX through lumbar puncture for patients with leptomeningeal metastases from lung cancer could improve their clinical symptoms, with no obvious adverse reactions and fairly good safety. KPS≥60 and absence of parenchymal metastases infer prolonged survival time, additionally, combination of EGFR-TKI treatment is effective in ameliorating the prognosis of patients with leptomeningeal metastases from lung cancer who received MTX intrathecal chemotherapy.