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

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。

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

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.