【摘要】 目的:探讨全脑照射(whole-brain radiation therapy,WBRT)和酪氨酸激酶抑制剂(tyrosine-kinase inhibitors,TKIs)对表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变(突变型和野生型)分型下非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移(brain metastasis,BM)患者总体生存(overall survival,OS)和颅内病灶控制影响的差异。方法:回顾性分析2013年1月至2015年1月河北医科大学第四医院首次诊治EGFR基因突变检测的NSCLC BM患者215例,随访至2016年12月1日。采用无颅内疾病进展生存(intracranial progression-free survival,i PFS)间接衡量颅内病灶控制。Kaplan-Meier曲线和多因素Cox模型评估WBRT(≥30Gy)和TKIs应用与OS和i PFS关系。采用中位生存(median survival time,MST)、危险比值(hazard ratio,HR)。结果:入组患者平均年龄58岁,女性52%,腺癌93%。EGFR突变型114例中应用WBRT 35例和TKIs 87例,其独立多因素调节HR为OS:1.135(P>0.200)和0.202(P<0.001),i PFS:1.122(P>0.200)和0.275(P<0.001);根据WBRT和TKIs应用,该人群分为4组:"WBRT联合TKIs(22例)"、"单纯TKIs(65例)"、"单纯WBRT(13例)"、"两者均无(14例)";分组OS MST依次别为14.1、15.3、7.1和4.3个月,i PFS MST为14.1、13.4、6.8和4.5个月;设"两者均无"组为参考时,"WBRT联合TKIs"、"单纯TKIs"和"单纯WBRT"3组多因素调节HR依次为OS:0.196(P=0.003),0.114(<0.001),0.434(P>0.200),i PFS:0.272(P=0.012),0.200(P<0.001),0.622(P>0.200);与"单纯TKIs"组比,"WBRT联合TKIs"组无生存差异,"单纯WBRT"组HR为OS:3.804(P=0.025)和i PFS:3.114(P=0.032)。EGFR野生型101例中应用WBRT 43例的OS的MST为11.3(7.1)个月,i PFS的MST为11.2(4.8)个月;"WBRT"调节HR为OS:0.539(P=0.105)和i PFS:0.485(P=0.048)。结论:TKIs能提高EGFR基因突变型NSCLC BM生存,但单独或增加WBRT无生存增益;WBRT能提高EGFR基因野生型NSCLC BM的iPFS。更多还原

【Abstract】 Objective: To compare overall survival(OS) and intracranial progression-free survival(iPFS) effects of whole-brain radiotherapy(WBRT) and tyrosine kinase inhibitors(TKIs) in NSCLC patients with brain metastases(BM) stratified by EGFR mutation status(mutant, wildtype). Methods: We performed a retrospective analysis of 215 NSCLC BM patients diagnosed in January 2013 to January 2015 with known EGFR status and followed up to December 1, 2016. Stratified Kaplan-Meier curves and multivariate Cox models were used to evaluate the effects of WBRT(defined as ≥30 Gy, "W") and TKIs(after BM, "T") on OS and iPFS independently and jointly. Two-sided P>0.20 was considered non-significant(ns). Results: In patients with BM, the mean age was 58 years, 52% were female, and 93% had adenocarcinoma. Those with EGFR mutations(114 patients) had "W"(35 patients) and "T"(87 patients) with adjusted hazard ratios(HRs)(P) of 1.135(ns) and 0.202(P<0.001) for OS, respectively, and 1.122(ns) and 0.275(P<0.001) for iPFS, respectively. "W+T"(22 patients), "T only"(65 patients), "W only"(13 patients), and "neither"(14 patients) had OS-median survival time(MST) of 14.1, 15.3, 7.1, and 4.3 months, respectively; their iPFSMST were 14.1, 13.4, 6.8, and 4.5 months, respectively. Their adjusted HRs(P) were 0.196(P=0.003), 0.114(P<0.001), 0.434(ns), 1.000(ref) for OS, respectively, and 0.272(P=0.012), 0.200(P<0.001), 0.622(ns), 1.000(ref) for iPFS, respectively. Compared with "T only," "W+T" was not associated with better survival and "W only" had adjusted HRs(P) of 3.804(P=0.025) for OS and 3.114(P=0.032) for iPFS. The EGFR wild-type(101 patients) used "W" in 43 patients with OS-MST of 11.3(7.1) and iPFS of 11.2(4.8) months; the adjusted HRs(P) of "W" were 0.539(P=0.105) for OS and 0.485(P=0.048) for iPFS. Conclusions: In EGFR-mutant NSCLC BM patients, TKIs are associated with improved survival, whether, WBRT alone or combined are not. In cases of EGFR wild-type, WBRT confers the improved the iPFS.更多还原