厄洛替尼治疗脑脊液检测EGFR敏感突变的肺腺癌一例

Response of Erlotinib in Lung Adenocarcinoma Harboring EGFR Sensitive Mutation in Cerebrospinal Fluid: Case Report

背景与目的脑是非小细胞肺癌(non-small cell lung cancer,NSCLC)常见的转移部位。有研究显示表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKI)可透过血脑屏障,发挥抗肿瘤作用。本例报道采用突变扩增阻滞系统(amplification refractory mutation system,ARMS)检测脑脊液EGFR突变指导临床治疗的可行性,并分析TKI治疗肺癌脑转移的疗效和安全性。方法腰穿取得脑脊液标本,检测颅内压力,检验常规、生化及肿瘤标志物,查找脱落细胞,采用ARMS法检测EGFR基因突变,得到阳性结果后给予盐酸厄洛替尼(erlotinib,tarceva,特罗凯)治疗,150 mg,每天1次。按照实体瘤疗效评价标准1.1版(Response Evaluation Criteriation in Solid Tumours,RECIST v1.1)评价客观疗效,按照不良反应通用术语标准4.0版(Common Terminology Criteria for Adverse Events v4.0,CTC AE v4.0)评估用药期间发生的不良事件。结果该患者多线治疗后,颅内病灶控制欠佳,脑脊液中发现异型细胞,EGFR基因19外显子缺失突变,服用厄洛替尼4周后,颅内客观疗效为部分缓解(partial response,PR),颅外客观疗效为疾病稳定(stable disease,SD),颅内无进展生存期(progression-free survival,PFS)10.5个月,总生存期(overall survival,OS)11个月。主要不良反应为皮疹(1级)。结论脑脊液检测EGFR突变可为制定治疗策略提供理论支持,根据不同的突变状态给予小分子靶向药物联合化疗,可分别控制颅内及颅外病灶。

Background and objective One of the most often distance metastasis site of non-small cell lung cancer（NSCLC） is brain and the standard treatment of brain metastasis was radiotheraphy including whole brain irradiation（WBI） and stereotactic radiotherapy（SRT）. It has been reported that epidermal growth factor receptor tyrosine kinase inhibitors（EGFR-TKIs） had the active response in brain metastasis of lung cancer. In the present study, we reported one case of EGFR 19 el in cerebrospinal fluid tested by ARMS got partial response given erlotinib. Methods Cerebrospinal fluid was collected through lumbar puncture, then cast-off cells and EGFR mutation was analysed. Erlotinib was given with dose of 150 mg, qd. Objective response was evaluated by Response Evaluation Criteriation in Solid Tumours（RECIST） v1.1 and adeverse events were evaluated according to Common Terminology Criteria for Adverse Events v4.0（CTC AE v4.0）. Results Heterocyst cells were found in cerebrospinal fluid and EGFR mutation was tested as 19 del. The patient achieved partial response（PR） of brain metastasis and the effective response in lung was stable disease（SD） after 4 weeks of erlotinib. The progression-free survival（PFS） and overall survival（OS） of brain metastasis was 10.5 months and 11 months respectively. The main adverse event was rash（Grade I）. Conclusion It was feasible to test EGFR mutation in cerebrospinal fluid and the combination of erlotinib with chemotheraphy would be an appropriate choice to those lung cancer patients who had brain metastasis harboring EGFR sensitive mutation.