针对脑转移的ALK靶向酪氨酸激酶抑制剂已经被开发出来，对于治疗非小细胞肺癌患者（NSCLC）的脑转移具有高效的穿脑效果，因此不再需要使用局部治疗（LT），例如SRS或治疗性颅骨切除术。在此，我们报告了一组接受ALECTINIB治疗的NSCLC患者的患者和病变水平的详细颅内结果和共突变基因组图谱。我们对于在2012年1月至2021年5月期间被诊断为脑转移的ALC融合阳性NSCLC患者进行了回顾性研究。结果变量包括颅内无进展生存期（iPFS）、总生存期（OS）、TKI治疗持续时间以及中枢神经系统反应率。通过MSK-IMPACT评估了肿瘤标本中的基因组特征，这是一种基于下一代测序（NGS）的基因组分析检测方法。 我们共包括了38名患者和114个颅内病变。其中12名患者还接受了同期局部治疗（SRS、WBRT或手术切除术）。在TKI+LT组中，最大BM直径更大（p<0.003），但尽管存在此差异，两组人群的iPFS（仅TKI，HR 1.21，95% CI 0.51-2.89; p=0.66）和OS（仅TKI，HR 5.99，95% CI 0.77-46.6; p=0.052）相似，且两组人群趋向于更有利的结果。SMARCA4的共同突变与更差的OS有关（HR 8.76，1.74-44.2；p=0.009） 我们的研究表明，使用TKI+LT治疗的ALK融合阳性NSCLC患者具有更大的BM和更高的术前神经症状发生率，但iPFS在两组人群之间相似。需要谨慎解读研究结果，因为我们的研究样本量较小。SMARCA4共同突变与更差的OS有关，这些发现需要进一步研究。版权所有©2023 Elsevier B.V.。

Highly effective brain-penetrant ALK-targeted tyrosine kinase inhibitors (TKIs) have been developed for the management of NSCLC patients with brain metastases (BM). Local therapy (LT) such as SRS or therapeutic craniotomy is increasingly being deferred for such patients. Herein we report detailed patient- and lesion-level intracranial outcomes and co-mutational genomic profiles from a cohort of NSCLC patients with BM treated with alectinib, with or without LT.We retrospectively reviewed ALK fusion-positive NSCLC patients with BMs who received alectinib at the diagnosis of BM from 1/2012 and 5/2021. Outcome variables included intracranial progression-free survival (iPFS), overall survival (OS), duration of TKI therapy, and CNS response rates. Genomic characteristics from tumor specimens were assessed with MSK-IMPACT, a next-generation sequencing (NGS)-based genomic profiling assay.A total of 38 patients with 114 CNS lesions were included. Twelve of these patients also received contemporaneous LT (SRS, WBRT, or surgical resection). Maximal BM diameter in the TKI + LT group was greater (p < 0.003) but despite this difference, iPFS (TKI only, HR 1.21, 95 % CI 0.51-2.89; p = 0.66) and OS (TKI only, HR 5.99, 95 % CI 0.77-46.6; p = 0.052) were similar between groups and trended towards more favorable outcomes with the addition of LT. SMARCA4 co-alterations were associated with inferior OS (HR 8.76, 1.74-44.2; p = 0.009).Our study demonstrated that patients with ALK fusion-positive NSCLC treated with TKI + LT had larger BM and higher likelihood of pre-treatment neurologic symptoms. Despite these differences, iPFS was similar between groups. Results should be interpreted with caution as our study was limited by an underpowered sample size. SMARCA4 co-alterations were associated with inferior OS and these findings warrant further investigation.Copyright © 2023 Elsevier B.V. All rights reserved.