EGFR突变肺腺癌脑转移患者放疗结合TKI的最佳时机

摘要

Objective To assess the efficacy and appropriate timing of brain radiotherapy (BRT) combined with tyrosine kinase inhibitors (TKI) for patients who developed brain metastases (BM) in epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma without prior TKI treatment.Method Fifty patients diagnosed as EGFR mutant lung adenocarcinoma who developed BM without prior TKI treatment were selected to analyze the treatment outcomes and failure patterns.Results With a median follow-up of 20 months,the 1-year overall survival (OS) rate of these patients was 82.0％,and the estimated OS time was 23 months.On univariate analysis,ECOG performance status,extracranial metastases,the number of BM,and the timing of brain radiotherapy combined with TKI were independently associated with OS.Multivariate analysis revealed that the number of BM and the timing of brain radiotherapy combined with TKI were prognostic factors.OS was significantly longer in the upfront BRT group (patients initiated TKI within 2 weeks of completing BRT) compared with the upfront TKI group (patients initiated BRT after TKI for intracranial progression) (28 months vs 18 months,P=0.011).The 1-year intracranial progression free survival (PFS) rate was 60.2％,and the estimated intracranial PFS time was 14 months.Multivariate analysis revealed that ECOG performance status and the timing of brain radiotherapy combined with TKI were associated with intracranial PFS.Intracranial PFS was improved in patients receiving upfront BRT compared with those receiving upfront TKI (17 months vs 10 months,P=0.019).Conclusion For patients who developed BM in EGFR mutant lung adenocarcinoma without prior TKI treatment,upfront BRT then TKI may be a proper choice.%目的 探讨表皮生长因子受体(EGFR)突变阳性,脑转移前未使用过酪氨酸激酶抑制剂(TKI)治疗的肺腺癌脑转移患者脑部放疗(BRT)结合TKI治疗的最佳时机.方法 收集50例EGFR突变阳性,脑转移前未使用TKI治疗的肺腺癌脑转移患者的临床资料,分析其治疗方案、疗效及失败模式.结果 50例患者中位随访时间20.0个月,1年总生存率为82.0％,预期生存时间为23个月.单因素分析显示ECOG评分、颅外转移灶、脑转移灶数目、放疗结合靶向时机与总生存期(OS)显著相关.多因素分析显示脑转移灶数目和放疗结合靶向治疗时机与OS有关,先BRT组(BRT结束2周内行TKI治疗)较先TKI组(TKI治疗颅内进展后行BRT)有明显的生存获益(28 m vs 18 m,P=0.011).所有患者1年颅内无进展生存率为60.2％,预期颅内PFS时间为14个月,多因素分析显示ECOG评分、放疗结合靶向时机与颅内PFS显著相关,先BRT组较先TKI组有较好的颅内PFS(17 m vs 10 m,P=0.019).结论 对于EGFR突变阳性、脑转移前未使用过TKI治疗的肺腺癌脑转移患者,放疗结束后行TKI可能是更好的选择.