不同病理亚型EGFR敏感突变肺腺癌靶向治疗的疗效与预后分析

Impact of distinct pathological subtypes on the efficacy and prognosis of targeted therapy in EGFR-sensitive mutant lung adenocarcinoma patients

目的评估不同病理亚型表皮生长因子受体(EGFR)敏感突变肺腺癌患者靶向治疗疗效与预后,为临床提供参考.方法回顾性收集2012-07-01-2017-10-31在山东省肿瘤医院(192例)和淄博市第一医院(18例)接受靶向治疗(TKI)的210例肺癌患者资料.其中,男91例,女119例;年龄<60岁86例,≥60岁124例.所有患者基因检测结果均为19-Del或L858R敏感突变,病理类型为肺腺癌.根据病理亚型的不同,将患者分为附壁型(19例)、腺泡型(150例)、乳头型(16例)、实体型(13例)和微乳头型(12例)5组.主要研究终点为无进展生存时间(PFS),次要研究终点为总体生存时间(OS).单因素生存分析采用Kaplan-Meier法和Log-rank检验,评估患者的PFS和OS,并制作生存曲线;多因素分析采用Cox比例风险回归分析来探讨预后影响因素.结果210例患者中53例患者生存,157例患者死亡.中位PFS:附壁型组36.6个月,腺泡型组20.0个月,乳头型组16.0个月,实体型组5.0个月,微乳头型组12.3个月,差异有统计学意义,P<0.001.中位OS:附壁型组60.0个月,腺泡型组39.5个月,乳头型组58.0个月,实体型组12.0个月,微乳头型组41.0个月,差异无统计学意义,P=0.06.影响PFS多因素回归分析:与附壁型组相比,腺泡型组、实体型组和微乳头型组进展风险差异均有统计学意义(腺泡型组:HR=1.72,95%CI为1.04~2.84,P=0.035;实体型组:HR=16.49,95%CI为7.50~36.24,P<0.001;微乳头型组:HR=2.27,95%CI为1.04~4.95,P=0.039).影响OS的多因素回归分析:与附壁型组相比,实体型组死亡风险是其的3.38倍,HR=3.38,95%CI为1.41~8.12,P=0.006.结论EGRF敏感突变患者TKI治疗后,腺泡型、实体型和微乳头型是无进展生存期预后不良的病理亚型,实体型是总生存期预后不良的病理亚型,可用于预测靶向治疗的疗效.

Objective To evaluate the efficacy and prognosis of targeted treatment in lung adenocarcinoma patients with dif-ferent pathological subtypes of epidermal growth factor receptor(EGFR)sensitive mutations,provide references for clini-cal practices.Methods The data of 210 lung cancer patients who received targeted therapy(TKI)in the Shandong Cancer Hospital and the Zibo First Hospital from July 1,2012,to October 31,2017,were retrospected.Among them,there were 91 males and 119 females,with 86 patients being under the age of 60 and 124 patients older.All patients pres-ented 19-Del or L858R sensitive mutations through gene testing,with pathologic type as lung adenocarcinoma.According to different pathologic subtypes,patients were divided into acinar type(19 cases),adenoid type(150 cases),papillary type(16 cases),solid type(13 cases),and micropapillary type(12 cases).The primary endpoint was progression-free survival time(PFS),and the secondary endpoint was overall survival time(OS).Single factor survival analysis utilized Kaplan-Meier method and Log-rank test to evaluate the patients'PFS and OS and to plot survival curves.The Cox propor-tional hazards regression analysis was used for multi-factor analysis to explore prognostic influencing factors.Results A-mong the 210 patients,53 survived,and 157 died.Median PFS was 36.6 months(acinar type),20.0 months(adenoid type),16.0 months(papillary type),5.0 months(solid type),12.3 months(micropapillary type),with significant sta-tistical difference,P<0.001.While the median OS was 60.0 months(acinar type),39.5 months(adenoid type),58.0 months(papillary type),12.0 months(solid type),41.0 months(micropapillary type),showing no statistically signifi-cant difference,P=0.06.Multi-factor regression analysis impacting PFS:Compared with acinar type,there were signifi-cant differences in progression risks in adenoid type,solid type and micropapillary type(adenoid type:HR=1.72,95%CI was 1.04-2.84,P=0.035;solid type:HR=16.49,95%CI was 7.50-36.24,P<0.001;micropapillary type:HR=2.27,95%CI was 1.04-4.95,P=0.039).Multi-factor regression analysis impacting OS:Compared to acinar type,the death risk of solid type was 3.38 times of it,HR=3.38,95%CI was 1.41-8.12,P=0.006.Conclusion After TKI treatment in EGFR sensitive mutation patients,adenoid type,solid type and micropapillary type are pathologic subtypes indicating inferior prognosis of PFS,solid type indicates inferior prognosis of OS,which can be utilized to pre-dict the efficacy of targeted therapy.