ImportanceCentral nervous system (CNS) metastases presenting as either brain parenchymal metastases or leptomeningeal metastases are diagnosed in up to 50% of patients with advanced non–small cell lung cancer during their disease course. While historically associated with a poor prognosis due to limited treatment options, the availability of an increasing number of targeted therapies with good CNS penetration has significantly improved clinical outcomes for these patients. This has occurred in parallel with a more nuanced understanding of prognostic factors.ObservationsMultiple clinical trials have reported that disease control can be observed with targeted therapies with adequate CNS penetration, particularly for patients with molecular alterations in EGFR, ALK, ROS1, and RET. For these tumors, systemic targeted therapy may be used first for the management of CNS metastases, prior to considering radiation therapy (RT). At the time of isolated progression in the CNS, RT may be considered for the progressing lesions with continuation of the same systemic therapy. For other molecular alterations as well as for patients treated with checkpoint inhibitors, data are not yet clear if systemic therapy is sufficient for untreated CNS metastases, and early RT may need to be integrated into the treatment planning. An increasing number of studies investigate the role that emerging techniques, such as the sequencing of tumor DNA from resected brain metastases tissue or cerebrospinal fluid or radiomics-based analysis of CNS imaging, can play in guiding treatment approaches.Conclusions and RelevanceWith multiple generations of targeted therapies now available, the treatment for CNS metastases should be tailored to the patients with consideration given to molecular testing results, CNS penetrance of systemic therapy, patient characteristics, and multidisciplinary review. More research is needed in understanding the clonal evolution of CNS metastases, and the development of novel therapeutics with CNS efficacy.

中文翻译：

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使用分子标志物以不断发展的方法靶向非小细胞肺癌中的 CNS 转移


重要性高达 50% 的晚期非小细胞肺癌患者在病程中诊断出表现为脑实质转移或软脑膜转移的中枢神经系统 （CNS） 转移。虽然由于治疗选择有限，历史上与不良预后相关，但越来越多的具有良好 CNS 渗透性的靶向治疗的可用性显着改善了这些患者的临床结果。这与对预后因素的更细致的理解同时发生。观察结果多项临床试验报告称，通过具有足够 CNS 渗透性的靶向治疗可以观察到疾病控制，特别是对于 EGFR、ALK、ROS1 和 RET 分子改变的患者。对于这些肿瘤，在考虑放疗 （RT） 之前，可以首先使用全身靶向治疗来管理 CNS 转移。在 CNS 孤立进展时，对于继续相同全身治疗的进展性病变，可考虑进行 RT。对于其他分子改变以及接受检查点抑制剂治疗的患者，目前尚不清楚全身治疗是否足以治疗未经治疗的 CNS 转移，可能需要将早期放疗纳入治疗计划。越来越多的研究调查了新兴技术的作用，例如从切除的脑转移组织或脑脊液中对肿瘤 DNA 进行测序或基于放射组学的 CNS 成像分析，可以在指导治疗方法中发挥作用。结论和相关性随着多代靶向治疗的出现，CNS 转移的治疗应根据患者量身定制，同时考虑分子检测结果、全身治疗的 CNS 外显率、患者特征和多学科审查。需要更多的研究来了解 CNS 转移的克隆进化，以及开发具有 CNS 疗效的新型疗法。