全脑照射联合靶向药物对HER2阳性乳腺癌脑转移患者生存的影响

Effects of Whole-brain Radiotherapy Combined with Targeted Therapy on Improving Survival of HER2-positive Breast Cancer Patients with Brain Metastases

目的探讨全脑照射(whole-brain radiation therapy, WBRT)联合靶向药物对HER2阳性乳腺癌脑转移(breast cancer brain metastases, BCBM)患者总体生存(overall survival, OS)和颅内病灶控制是否有增益作用。方法回顾性分析2013—2015年首次诊治为HER2阳性BCBM女性患者39例,随访至2016年12月1日。采用无疾病进展生存(progression-free survival, PFS)间接衡量病灶控制。主变量为WBRT(≥20 Gy,有vs.无)和靶向药物应用(围放疗期,有vs.无)。采用K-M曲线和多因素Cox模型分析对OS和PFS的影响。结果平均年龄52岁,脑转移灶≥4个者46%,ER/PR阳性64%,Ki-67高表达(≥14%)74%;WBRT 46%(18例),靶向治疗38%(15例)。K-M曲线1年死亡率47%、治疗失败率(死亡/脑复发/新灶)58%;中位OS 13.3月和PFS 10.1月。多因素独立评估WBRT的HR(P)为OS 0.170(0.002)和PFS 0.107(<0.001)。WBRT联合靶向药物、单纯靶向药物、单纯WBRT和"均无"(即其他治疗组)例数(中位OS)依次为8例(15.1月)、7例(14.7月)、10例(17.6月)和14例(4.3月)。以上各组多因素评估OS的HR(P)分别为0.049(<0.001)、0.243(0.077)、0.154(0.007)、1.000(参考组);PFS结果类似。结论 WBRT联合靶向药物对HER2阳性BCBM患者生存提高有增益作用。

Objective To investigate if the whole-brain radiation therapy(WBRT)and targeted therapy(TTx)have the enhanced effect on improving overall survival(OS)and intracranial tumor control measured indirectly by progression-free survival(PFS)in HER2-positive breast cancer brain metastases(BCBM)patients.Methods We conducted a retrospective analysis of 39 female HER2-positive BCBM patients admitted in 2013-2015 and followed up till December 1st,2016.WBRT was defined as≥20 Gy and all TTx were initiated before WBRT.Kaplan-Meier curves and multivariate Cox regression models were used for analyzing OS and PFS.Results Average age was 52 years old;46%patients were with≥4 BM lesions,64%with ER/PR+,74%with high Ki-67 expression(≥14%);18(46%)patients received WBRT and 15(38%)received TTx.One-year mortality was 47%and treatment failure(death or new/relapsed BM)rate was 58%.Median survival time(MST)of OS and PFS were 13.3 and 10.1 months,respectively.Multivariate adjusted HR(P)of WBRT were 0.170(0.002)for OS and 0.107 for PFS(P<0.001).The number(median OS)of patients who received WBRT&TTx,TTx alone,WBRT alone and neither were 8(15.1),7(14.7),10(17.6)and 14(4.3),respectively.Their multivariate adjusted HR(P)for OS were 0.049(P<0.001),0.243(0.077),0.154(0.007)and 1.000(ref.),respectively.The analysis on PFS had similar results.Conclusion WBRT and targeted therapy have the enhanced effect on improving OS and PFS of HER2-positive BCBM patients.