Tatineni Vineeth, O'Shea Patrick J, Saxena Shreya, Khosla Atulya A, Ozair Ahmad, Kotecha Rupesh R, Jia Xuefei, Rauf Yasmeen, Murphy Erin S, Chao Samuel T, Suh John H, Peereboom David M, Ahluwalia Manmeet S
Rosa Ella Burkhart Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Cancers (Basel). 2023 Jun 1;15(11):3015. doi: 10.3390/cancers15113015.
Traditionally, brain metastases have been treated with stereotactic radiosurgery (SRS), whole-brain radiation (WBRT), and/or surgical resection. Non-small cell lung cancers (NSCLC), over half of which carry EGFR mutations, are the leading cause of brain metastases. EGFR-directed tyrosine kinase inhibitors (TKI) have shown promise in NSCLC; but their utility in NSCLC brain metastases (NSCLCBM) remains unclear. This work sought to investigate whether combining EGFR-TKI with WBRT and/or SRS improves overall survival (OS) in NSCLCBM.
A retrospective review of NSCLCBM patients diagnosed during 2010-2019 at a tertiary-care US center was performed and reported following the 'strengthening the reporting of observational studies in epidemiology' (STROBE) guidelines. Data regarding socio-demographic and histopathological characteristics, molecular attributes, treatment strategies, and clinical outcomes were collected. Concurrent therapy was defined as the combination of EGFR-TKI and radiotherapy given within 28 days of each other.
A total of 239 patients with EGFR mutations were included. Of these, 32 patients had been treated with WBRT only, 51 patients received SRS only, 36 patients received SRS and WBRT only, 18 were given EGFR-TKI and SRS, and 29 were given EGFR-TKI and WBRT. Median OS for the WBRT-only group was 3.23 months, for SRS + WBRT it was 3.17 months, for EGFR-TKI + WBRT 15.50 months, for SRS only 21.73 months, and for EGFR-TKI + SRS 23.63 months. Multivariable analysis demonstrated significantly higher OS in the SRS-only group (HR = 0.38, 95% CI 0.17-0.84, = 0.017) compared to the WBRT reference group. There were no significant differences in overall survival for the SRS + WBRT combination cohort (HR = 1.30, 95% CI = 0.60, 2.82, = 0.50), EGFR-TKIs and WBRT combination cohort (HR = 0.93, 95% CI = 0.41, 2.08, = 0.85), or the EGFR-TKI + SRS cohort (HR = 0.46, 95% CI = 0.20, 1.09, = 0.07).
NSCLCBM patients treated with SRS had a significantly higher OS compared to patients treated with WBRT-only. While sample-size limitations and investigator-associated selection bias may limit the generalizability of these results, phase II/III clinicals trials are warranted to investigate synergistic efficacy of EGFR-TKI and SRS.
传统上，脑转移瘤的治疗方法包括立体定向放射外科治疗（SRS）、全脑放疗（WBRT）和/或手术切除。非小细胞肺癌（NSCLC）是脑转移瘤的主要病因，其中超过一半携带表皮生长因子受体（EGFR）突变。表皮生长因子受体导向的酪氨酸激酶抑制剂（TKI）在非小细胞肺癌治疗中显示出前景；但其在非小细胞肺癌脑转移（NSCLCBM）中的效用仍不明确。本研究旨在探讨EGFR-TKI联合WBRT和/或SRS是否能提高NSCLCBM患者的总生存期（OS）。
对2010年至2019年在美国一家三级医疗中心诊断为NSCLCBM的患者进行回顾性研究，并按照“加强流行病学观察性研究报告”（STROBE）指南进行报告。收集了有关社会人口统计学和组织病理学特征、分子属性、治疗策略和临床结局的数据。同步治疗定义为EGFR-TKI和放疗在彼此28天内联合使用。
共纳入239例EGFR突变患者。其中，32例仅接受了WBRT治疗，51例仅接受了SRS治疗，36例仅接受了SRS和WBRT治疗，18例接受了EGFR-TKI和SRS治疗，29例接受了EGFR-TKI和WBRT治疗。仅接受WBRT治疗组的中位总生存期为3.23个月，SRS + WBRT组为3.17个月，EGFR-TKI + WBRT组为15.50个月，仅接受SRS治疗组为21.73个月，EGFR-TKI + SRS组为23.63个月。多变量分析显示，与WBRT参照组相比，仅接受SRS治疗组的总生存期显著更长（风险比[HR]=0.38，95%置信区间[CI]为0.17 - 0.84，P = 0.017）。SRS + WBRT联合治疗组（HR = 1.30，95% CI = 0.60，2.82，P = 0.50）、EGFR-TKIs和WBRT联合治疗组（HR = 0.93，95% CI = 0.41，2.08，P = 0.85）或EGFR-TKI + SRS组（HR = 0.46，95% CI = 0.20，1.09，P = 0.07）的总生存期无显著差异。
与仅接受WBRT治疗的患者相比，接受SRS治疗的NSCLCBM患者的总生存期显著更高。虽然样本量限制和研究者相关的选择偏倚可能会限制这些结果的普遍性，但仍有必要进行II/III期临床试验来研究EGFR-TKI和SRS的协同疗效。
