SRS治疗时机对EGFR突变型肺腺癌脑转移患者的生存影响

Effect of SRS Treatment Timing on Survival of EGFR-mutated Lung Adenocarcinoma with Brain Metastasis

目的探讨在酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗的表皮生长因子受体(epidermal growth factor receptor,EGFR)突变肺腺癌脑转移患者中立体定向放射外科(stereotactic radiosurgery,SRS)的治疗时机。方法收集2018年1月~2020年12月于郑州大学第五附属医院就诊的90例EGFR突变型肺腺癌脑转移患者的病例资料,均接受TKI治疗。根据SRS的治疗时机不同分为2个治疗组:确诊为肺腺癌脑转移后即行SRS的称为早SRS组(n=52),接受TKI治疗待脑部转移灶进展后再行SRS的称为晚SRS组(n=38)。比较两组的客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)、颅内无进展生存期(intracranial progression-free survival,iPFS)和总生存期(overall survival,OS)。采用多因素COX回归模型进行预后分析。结果两组的ORR(59.6%vs 50.0%,P=0.365)和DCR(76.9%vs 73.7%,P=0.724)比较,差异无统计学意义。全组中位OS和iPFS分别为31.5个月和12.5个月,早SRS组的OS比晚SRS组明显延长(35.5个月vs 27个月,P=0.001);早SRS组的iPFS也明显优于晚SRS组(15.0个月vs 11.5个月,P=0.004)。全组无脑转移症状的患者中位OS较有脑转移症状患者延长(35.5个月vs 27.0个月,P=0.011)。多因素COX回归分析结果显示,早SRS治疗是患者OS和iPFS的保护因素(HR<1,P<0.05),Lung-mol GPA评分为3.5~4.0分是患者OS的保护因素(HR<1,P<0.01)。结论晚期EGFR突变型肺腺癌伴脑转移患者,基于TKI药物治疗下,脑转移确诊后早期行SRS治疗颅内控制效果更佳,生存获益更大。

Objective To investigate the timing of stereotactic radiosurgery(SRS)in lung adenocarcinoma with epidermal growth factor receptor(EGFR)mutation treated with tyrosine kinase inhibitor(TKI).Methods A total of 90 patients with EGFR-mutated lung adenocarcinoma patients with brain metastasis admitted to the Fifth Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were collected.All patients received TKI treatment and were divided into two treatment groups according to the timing of SRS treatment:those who received SRS immediately after the diagnosis of lung cancer brain metastasis were called early SRS group(n=52),and those who received TKI treatment and then SRS after the progression of brain metastasis were called deferred SRS group(n=38).Objective response rate(ORR),disease control rate(DCR),intracranial progression-free survival(iPFS)and overall survival(OS)were compared between the two groups.Multivariate COX regression model was used to analyze the prognosis.Results There was no significant difference in ORR(59.6%vs 50.0%,P=0.365)and DCR(76.9%vs 73.7%,P=0.724)between the two groups.The median OS and iPFS of the whole group were 31.5months and 12.5months,respectively.The OS of the early SRS group was significantly longer than that of the late SRS group(35.5months vs 27.0months,P=0.001).iPFS was also significantly better in the early SRS group than in the late SRS group(15.0months vs 11.5months,P=0.004).The median OS was longer in patients with no symptoms of brain metastases than in patients with symptoms of brain metastases(35.5months vs 27.0months,P=0.011).Multivariate COX regression analysis showed that early SRS treatment was a protective factor for OS and iPFS(HR<1,P<0.05),and Lung-mol GPA score of 3.5-4.0 was a protective factor for OS(HR<1,P<0.01).Conclusion For patients with advanced EGFR-mutated lung adenocarcinoma with brain metastases,early SRS treatment after diagnosis of brain metastases has better intracranial control effect and greater survival benefit.