Impact of EGFR mutation subtypes and TKI generations on clinical outcomes in lung adenocarcinoma patients with brain metastases treated with gamma knife radiosurgery.

IF 3.1 2区 医学 Q2 CLINICAL NEUROLOGY
Journal of Neuro-Oncology Pub Date : 2025-12-01 Epub Date: 2025-09-16 DOI:10.1007/s11060-025-05149-z
Haewon Roh, Chan Park, Won Kim, Juwhan Choi, Sung Yong Lee, Jong Hyun Kim
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引用次数: 0

Abstract

Background: Brain metastases are a common and severe complication in patients with lung adenocarcinoma (ADC) harboring epidermal growth factor receptor (EGFR) mutations. Gamma Knife Radiosurgery (GKRS) is a standard treatment for brain metastases, and its efficacy may be influenced by the type of EGFR mutation and the generation of tyrosine kinase inhibitors (TKIs) used. This retrospective study evaluated the impact of EGFR mutation subtypes (exon 19 deletion vs. exon 21 L858R) and TKI generations on clinical outcomes in patients with lung ADC treated with GKRS.

Methods: A total of 55 patients and 136 brain metastases were analyzed from January 2017 to December 2023. Tumor response was assessed based on local failure and distant brain failure, defined as tumor progression at the treated site and new brain metastases outside the GKRS-treated regions, respectively. The Kaplan-Meier method and univariate and multivariate analyses using Cox proportional hazard regression models were used to identify prognostic factors for local failure, and distant brain failure.

Results: The study found that second- and third-generation TKIs, such as afatinib and osimertinib, provided significantly better local control compared to first-generation TKIs (hazard ratio [HR] = 0.12, p = 0.017). Furthermore, tumors with exon 19 deletion demonstrated improved distant brain control compared to those with exon 21 L858R substitution (HR = 2.18, p = 0.048). These findings suggest that mutation type and TKI generation are independent prognostic factors for clinical outcomes following GKRS.

Conclusion: This study suggests that both the generation of TKIs and the specific EGFR mutation subtype may influence clinical outcomes following GKRS in lung ADC patients with brain metastases. These findings may aid in stratifying patients and optimizing treatment strategies in clinical practice.

EGFR突变亚型和TKI代对伽玛刀放射治疗肺腺癌脑转移患者临床结局的影响
背景:脑转移是表皮生长因子受体(EGFR)突变肺腺癌(ADC)患者常见且严重的并发症。伽玛刀放射手术(GKRS)是脑转移的标准治疗方法,其疗效可能受到EGFR突变类型和酪氨酸激酶抑制剂(TKIs)的影响。这项回顾性研究评估了EGFR突变亚型(外显子19缺失vs外显子21 L858R)和TKI代对GKRS治疗肺ADC患者临床结果的影响。方法:对2017年1月至2023年12月共55例患者和136例脑转移患者进行分析。肿瘤反应是根据局部衰竭和远处脑衰竭来评估的,分别定义为治疗部位的肿瘤进展和gkrs治疗区域外的新脑转移。采用Kaplan-Meier方法和单因素及多因素分析,采用Cox比例风险回归模型确定局部脑衰竭和远端脑衰竭的预后因素。结果:研究发现,与第一代TKIs相比,第二代和第三代TKIs,如阿法替尼和奥西替尼,提供了更好的局部控制(风险比[HR] = 0.12, p = 0.017)。此外,与外显子21 L858R替换的肿瘤相比,外显子19缺失的肿瘤表现出更好的远端脑控制(HR = 2.18, p = 0.048)。这些发现表明突变类型和TKI的产生是GKRS后临床结果的独立预后因素。结论:本研究提示TKIs的产生和特异性EGFR突变亚型都可能影响肺ADC脑转移患者GKRS后的临床结果。这些发现可能有助于在临床实践中对患者进行分层和优化治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Neuro-Oncology
Journal of Neuro-Oncology 医学-临床神经学
CiteScore
6.60
自引率
7.70%
发文量
277
审稿时长
3.3 months
期刊介绍: The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
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