Table_3_Upfront Cranial Radiotherapy vs. EGFR Tyrosine Kinase Inhibitors Alone for the Treatment of Brain Metastases From Non-small-cell Lung Cancer: A Meta-Analysis of 1465 Patients.DOCX

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is revolutionizing the management of brain metastases (BMs). This study was to explore the value of upfront cranial radiotherapy (RT) in EGFR-mutated non-small cell lung cancer (NSCLC) with BMs compared with EGFR-TKIs alone.
Methods: We searched all topic-related comparative articles in public databases (MEDLINE, EMBASE, Cochrane Library, and Web of Science) and conference proceedings. Outcomes of interest were intracranial objective response rate (ORR), overall survival (OS), and intracranial progression-free survival (PFS). Statistical analyses were calculated using Review Manager 5.3 software.
Results: Thirteen comparative studies that included a total of 1,456 patients were eligible. Upfront brain RT had significantly higher OS (HR = 0.78, 95% CI = 0.65–0.93, P = 0.005) than EGFR-TKI alone. Upfront RT plus TKI had superior OS (HR = 0.71, 95% CI = 0.58–0.86, P = 0.0005) and intracranial PFS (HR = 0.69, 95% CI = 0.49–0.99, P = 0.04). The pooled data favored upfront whole brain RT (WBRT) plus TKI in terms of intracranial PFS (HR = 0.64, 95% CI = 0.48–0.85, P = 0.002) and OS (HR = 0.75, 95% CI = 0.57–1, P = 0.05). Upfront stereotactic radiosurgery (SRS) was associated with better OS (HR = 0.37, 95% CI = 0.26–0.54, P < 0.00001). Similar results were observed when analysis was restricted to the use of erlotinib or geftinib.
Conclusions: The upfront use of brain RT seemed critical, especially for SRS. Upfront administration of upfront WBRT plus EGFR-TKI had better survival outcomes and seemed superior to EGFR-TKI alone.

【背景】表皮生长因子受体酪氨酸激酶抑制剂（Epidermal growth factor receptor tyrosine kinase inhibitors, EGFR-TKIs）正彻底改变脑转移瘤（brain metastases, BMs）的临床诊疗格局。本研究旨在对比单纯EGFR-TKIs治疗方案，探讨初始颅脑放疗（upfront cranial radiotherapy, RT）在伴脑转移的EGFR突变型非小细胞肺癌（non-small cell lung cancer, NSCLC）中的临床应用价值。
【方法】我们检索了公共数据库（MEDLINE、EMBASE、Cochrane图书馆、Web of Science）及学术会议论文集中所有与主题相关的对照研究。本研究的主要结局指标包括颅内客观缓解率（intracranial objective response rate, ORR）、总生存期（overall survival, OS）及颅内无进展生存期（intracranial progression-free survival, PFS）。统计学分析采用RevMan 5.3（Review Manager 5.3）软件完成。
【结果】共计13项符合纳入标准的对照研究，累计纳入1456例患者。相较于单纯EGFR-TKIs治疗，初始颅脑放疗组患者的总生存期显著更长（风险比（hazard ratio, HR）=0.78，95%置信区间（95% confidence interval, 95%CI）=0.65~0.93，P=0.005）。初始放疗联合TKI治疗方案的总生存期（HR=0.71，95%CI=0.58~0.86，P=0.0005）及颅内无进展生存期（HR=0.69，95%CI=0.49~0.99，P=0.04）均更优异。合并分析数据显示，初始全脑放疗（whole brain RT, WBRT）联合TKI治疗在颅内无进展生存期（HR=0.64，95%CI=0.48~0.85，P=0.002）及总生存期（HR=0.75，95%CI=0.57~1.00，P=0.05）方面更具优势。初始立体定向放射外科（stereotactic radiosurgery, SRS）与更优的总生存期显著相关（HR=0.37，95%CI=0.26~0.54，P<0.00001）。当分析仅限定于厄洛替尼（erlotinib）或吉非替尼（geftinib）的使用场景时，得到了一致的研究结果。
【结论】初始颅脑放疗的临床应用似乎具有关键价值，尤其针对立体定向放射外科治疗。初始全脑放疗联合EGFR-TKIs治疗可获得更优的生存结局，且显著优于单纯EGFR-TKIs治疗方案。