EGFR不同突变亚型与肺腺癌脑转移预后的相关性分析

Association between epidermal growth factor receptor mutation subtypes and the prognosis of brain metastases in patients with lung adenocarcinoma

目的探讨肺腺癌脑转移患者EGFR不同突变亚型与预后的相关性。方法回顾分析2010-2015年本院收治的经EGFR基因突变检测的肺腺癌脑转移患者256例临床资料，筛选脑转移的预后影响因素。Kaplan—Meier法计算生存率Logrank法检验和单因素预后分析，Cox模型多因素预后分析。结果全组患者中位生存期为10．13个月。单因素分析显示性别、EGFR突变状态、19外显子缺失突变、脑转移时KPS评分、靶向治疗与预后有关（P=0．006、0．001、0．010、0．000、0．003），多因素分析显示脑转移时KPS评分、19外显子缺失突变为脑转移患者预后影响因素（P=0．000、0．045）。将全组病例纳入RPA预后分级指数，检验显示差异有统计学意义（P=0．000）。结论19外显子缺失突变是肺腺癌脑转移患者的预后影响因素，可以考虑将其纳入肺腺癌脑转移瘤预后评分系统。EGFR—TKI使EGFR基因突变肺腺癌脑转移患者生存获益，尤其是19外显子缺失突变患者。

Objective To explore the association between epidermal growth factor receptor （EGFR） mutation subtypes and the prognosis of brain metastasis in patients with lung adenocarcinoma. Methods A retrospective analysis was performed on the clinical data of 256 patients who were admitted to our hospital and confirmed with brain metastases of lung adenocarcinoma by EGFR mutation detection from 2010 to 2015. The prognostic factors for brain metastases were analyzed. The survival rate was calculated by the Kaplan-Meier method and analyzed by the log-rank test. The univariate and multivariate prognostic analyses were performed by the log-rank test and the Cox proportional hazards model. Results The median survival time was 10. 13 months in all patients. The univariate analysis showed that sex, EGFR mutation status,exon 19 deletion, the Karnofsky Performance Status （KPS） score of brain metastases, and targeted therapy were prognostic predictors （ P= 0. 006, 0. 001,0. 010, 0. 000, 0. 003 ）. The multivariate analysis showed that the KPS score and exon 19 deletion were prognostic factors for brain metastases （P= 0. 000, 0. 045）. When grouped into the recursive partitioning analysis classes, all the patients were split into three subgroups with significantly different prognosis （P = 0. 000）. Conclusions Exon 19 deletion is a prognostic predictor of brain metastases in patients with lung adenocarcinoma,which can be integrated into the prognosis scoring system for brain metastases of lung adenocarcinoma. EGFR tyrosine kinase inhibitors improve the survival in patients with brain metastases of lung adenocarcinoma and EGFR mutation, particularly, in those with exon 19 deletion_