目的：观察阿帕替尼联合放疗同步多西他赛与顺铂化疗治疗驱动基因阴性非小细胞肺癌（NSCLC）脑转移瘤患者的近期疗效和安全性。方法：收集2018 年6 月至2019 年6 月在我院收治的NSCLC脑转移患者72 例，二代基因测序（NGS）显示驱动基因阴性，数字随机分组法分为对照组36 例、治疗组36 例，对照组接受多西他赛、顺铂方案化疗2 个周期及同步脑转移瘤放疗，治疗组在观察组基础上给予阿帕替尼抗血管生成治疗。主要研究终点：确认有效率（cORR）和疾病控制率（DCR）；次要研究终点：无进展生存期（PFS），生存质量（QOL）评分，血清癌胚抗原（CEA），血管内皮生长因子（VEGF）及药物不良事件（AE）发生率。结果：与对照组相比，治疗组cORR和DCR明显提高[41.67%（15/36）vs 33.33%（12/36）、80.56%（29/36）vs 69.44%（25/36），均P<0.05]；中位PFS 明显延长（5.9 vs 4.6 个月，P<0.05）；血清CEA和VEGF值显著降低[ （16.5±2.3）vs（22.9±3.7）ng/ml、（291.6±42.6）vs（479.3±50.2）pg/ml，P<0.05]；而QOL 评分治疗组[ （69.5±8.5）分]虽略高于对照组[ （64.1±7.3）分]，但差异无统计学意义（P>0.05）。两组患者在急性脑水肿、胃肠反应、骨髓抑制、肝功能减退发生率的差异无统计学意义（均P>0.05），治疗组口腔黏膜炎、手足综合征、高血压、蛋白尿发生率明显高于对照组（均P<0.05）。结论：阿帕替尼联合放化疗在驱动基因阴性NSCLC脑转移患者中的疗效明显优于单纯放化疗，且不良反应可控，值得临床推荐。

Objective: To observe the short-term efficacy and safety of Apatinib combined with radiotherapy and concurrent docetaxel and cisplatin chemotherapy in driver-gene-negative non-small cell lung cancer (NSCLC) patients with brain metastases. Methods: A total of 72 NSCLC patients with brain metastases, who were treated in our hospital from June 2018 to June 2019, were enrolled in this study. The driver gene was proved to be negative by next generation sequencing (NGS). The patients were divided into control group (36 cases) and treatment group (36 cases) by Digital random grouping method.The control group received 2 cycles of chemotherapy with docetaxel and cisplatin and concurrent radiotherapy for brain metastases, and the treatment group was given Apatinib anti-angiogenic treatment based on the regimen in control group. Primary study endpoints: confirmed objective response rate (cORR) and disease control rate (DCR); Secondary study endpoints: progression-free survival (PFS), quality of life (QOL) score, serum carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF), and incidence of adverse drug events (AE). Results: Compared with the control group, cORR and DCR in treatment group were significantly improved [41.67% (15/36) vs 33.33% (12/36), 80.56% (29/36) vs 69.44% (25/36), all P<0.05], the median PFS was significantly prolonged (5.9 vs 4.6 months, P<0.05), and serum CEA and VEGF levels were significantly reduced [(16.5±2.3) vs (22.9±3.7) ng/ml, (291.6±42.6) vs (479.3±50.2) ng/L, all P<0.05], while the QOL score was slightly increased, but the difference was not statistically significant [(69.5±8.5) points vs (64.1±7.3) points, P>0.05]. There was no statistically significant difference in the incidence of acute brain edema, gastrointestinal reaction, bone marrow suppression, and liver dysfunction between the two groups of patients (all P>0.05); however, the incidences of oral mucositis, hand-foot syndrome,hypertension and proteinuria in the treatment group were significantly higher than those in the control group (all P<0.05). Conclusion:The efficacy of Apatinib combined with radiochemotherapy in driver-negative NSCLC patients with brain metastases is significantly better than that of radiochemotherapy alone, and the adverse reactions can be controlled. It is worthy of clinical recommendation.

中国科学院合肥肿瘤医院院长基金（YZJJ2019A02）