高通量药物敏感性筛选系统在非小细胞肺癌伴恶性胸腔积液治疗中的应用  

Application of high-throughput drug sensitivity screening system in the treatment of non-small cell lung cancer with malignant pleural effusion

作　　者：张宇[1] 吴晓渊[2] 管丽华[3] 刘译远 彭星月 谢海燕[1] 胡玮 郝可可[1] 夏宁[1] 陆国军[1] 侯志波[1] ZHANG Yu;WU Xiaoyuan;GUAN Lihua;LIU Yiyuan;PENG Xingyue;XIE Haiyan;HU Wei;HAO Keke;XIA Ning;LU Guojun;HOU Zhibo(Department of Respiratory Medicine,Nanjing Chest Hospital,The Affiliated Brain Hospital of Nanjing Medical University,Nanjing 210029,China;Central laboratory,Nanjing Chest Hospital,The Affiliated Brain Hospital of Nanjing Medical University,Nanjing 210029,China;Information Department,Nanjing Chest Hospital,The Affiliated Brain Hospital of Nanjing Medical University,Nanjing 210029,China;Nanjing TechBoon Clinical Medicine Institute,Nanjing 210018,China)

机构地区：[1]南京市胸科医院/南京医科大学附属脑科医院呼吸一科,南京210029 [2]南京市胸科医院/南京医科大学附属脑科医院中心实验室,南京210029 [3]南京市胸科医院/南京医科大学附属脑科医院信息科,南京210029 [4]南京融康博临床医学研究院,南京210018

出　　处：《上海交通大学学报（医学版）》2022年第1期82-89,共8页Journal of Shanghai Jiao tong University:Medical Science

基　　金：江苏省卫生计生委医学科研课题面上项目(H2018030)。

摘　　要：目的·探讨体外高通量药物敏感性筛选系统指导非小细胞肺癌(non-small cell lung cancer,NSCLC)伴恶性胸腔积液(malignant pleural effusion,MPE)患者个体化治疗的可行性。方法·纳入2019年1月—2020年5月就诊于南京市胸科医院的30例NSCLC伴MPE患者,收集并分离胸水中的肿瘤细胞,培养原代细胞,使用自动数字荧光扫描仪的高通量药物敏感性筛选系统,检测30种化学治疗(化疗)药物和分子靶向药物的体外直接敏感性,评估药物敏感检测结果与患者临床治疗效果的一致性。结果·胸腔积液原代肿瘤细胞的体外药物敏感性检测结果显示药物反应存在很大的异质性。大部分原代细胞对表柔比星、洛铂、吉西他滨和伊立替康敏感。23例患者可评价其临床疗效,对于表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变阳性的初治NSCLC晚期患者,靶向治疗的效果与高通量药敏试验结果的一致性为44.4%(4/9);对于EGFR突变阴性的患者和EGFR突变阳性接受靶向治疗耐药的晚期NSCLC患者,采用化疗的效果与体外高通量药物敏感试验结果一致率为85.7%(12/14)。结论·基于NSCLC患者MPE原代细胞培养的高通量药物敏感性试验与化疗的临床疗效一致性较高,有助于临床制定个体化化疗方案。Objective·To explore the feasibility of individualized treatment of malignant pleural effusion(MPE) patients with nonsmall cell lung cancer(NSCLC) guided by in vitro high-throughput drug sensitivity screening system. Methods·Thirty NSCLC patients with MPE treated in Nanjing Chest Hospital from January 2019 to May 2020 were included. The tumor cells in MPE were collected and isolated, and primary cells were cultured. The ex vivo drug sensitivity of primary cells was assessed for 30 chemotherapeutical and molecular targeted drugs by using the high-throughput drug sensitivity screening system of automated digital fluorescence imager. The consistency between the drug sensitivity assay results and the clinical efficacy of patients was evaluated. Results·The ex vivo drug sensitivity results of primary tumor cells cultured from MPE revealed considerable heterogeneity in drug response. Most of the primary cells were sensitive to Epirubicin, Lobaplatin, Gemcitabine and Irinotecan.Clinical efficacy of 23 patients can be evaluated. For patients with previously untreated, epidermal growth factor receptor(EGFR)mutation-positive advanced NSCLC, the consistency between the efficacy of targeted therapy and the high-throughput drug sensitivity assay results was 44.4%(4/9). For the EGFR negative untreated patients and EGFR mutation-positive advanced NSCLC patients with acquired resistance to targeted treatment, the consistency between the therapeutic effect of chemotherapy and the highthroughput drug sensitivity assay results was 85.7%(12/14). Conclusion·The high-throughput drug sensitivity assay based on MPE primary cell culture in NSCLC patients has a high consistency with the clinical efficacy of chemotherapy, which is helpful for decision-making of personalized chemotherapy.

关 键 词：非小细胞肺癌 胸腔积液 体外药物敏感试验 个体化治疗 

分 类 号：R734.2[医药卫生—肿瘤]