Timing of Brain Radiation Therapy Impacts Outcomes in Patients with Non-small Cell Lung Cancer Who Develop Brain Metastases

背景与目的放疗联合化疗或靶向治疗仍然是非小细胞肺癌脑转移患者的首选治疗。本研究旨在探讨脑放疗时机的选择及推迟脑放疗对于患者疗效和生存期的影响。方法2003年5月-2015年12月，就诊于我中心确诊为非小细胞肺癌脑转移且接受过脑放疗及全身治疗（包括化疗和靶向治疗）的患者共198例入组了本研究。127例接受了同时性的全身治疗和脑放疗（早放疗组）。71例患者接受了延迟性的脑放疗：完成至少2周期全身治疗后才接受脑放疗（晚放疗组）。早放疗组和晚放疗组患者治疗前的脑转移预后评分（DS-GPA评分）均衡无偏倚。结果早放疗组患者的中位生存时间（overall survival, OS）与晚放疗组相比明显延长（17.9个月vs 12.6个月，P=0.038），早放疗组患者的无进展生存期（progression-free survival, PFS）也优于晚放疗组（4.0个月vs 3.0个月，P<0.01）。3级-4级放化疗不良反应的发生率两组间无明显差异。确诊脑转移后，一线使用酪氨酸激酶抑制剂（ tyrosine kinase inhibitor, TKI）药物可能延长患者的OS（17.9个月vs 15.2个月，P=0.289），但无明显统计学差异。在整个疾病进展过程中曾经使用TKI类药物与从未使用过TKI药物相比，患者的OS延长（20.0个月vs 10.7个月，P<0.01）。结论对于非小细胞肺癌脑转移患者，推迟脑放疗可能会影响患者的生存期。这一发现仍需要前瞻性多中心的随机对照研究来证实。Background and objective Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). hTe aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes.Methods Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemo-therapy or targeted therapy) were identiifed. hTe rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no signiifcant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease speciifc-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group.Results Me-dian overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 monthsvs 12.6 months;P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 monthsvs 3.0 months;P<0.01). Receiving tyrosine kinase inhibitor (TKI) therapy atfer the diagnosis of brain metastases as any line therapy improved the OS (20.0 monthsvs 10.7 months;P<0.01), whereas receiving TKI as ifrst line therapy did not (17.9 monthsvs 15.2 months;P=0.289).Conclusion Our study suggests that the use of deferred brain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospec-tive multi-central randomized study is imminently needed.PubMed中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)8508-5141