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

李振生; 孔德友; 段学娟; 申晓菲; 申东星; 张钧

doi:10.3971/j.issn.1000-8578.2018.18.0324

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

摘要

摘要:
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。

Abstract:
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.

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