对于源于癌基因成瘾性肺癌的大范围脑转移（BrM）病例，具有高中枢神经系统反应率的酪氨酸激酶抑制剂（TKIs）有可能降低中枢神经系统疾病负担，避免先期全脑放疗（WBRT），并将某些患者转化为局部立体定向放射外科（SRS）的候选人。我们描述了在我们的机构自2012年至2021年期间，使用最新一代中枢神经系统活性TKIs，包括奥西单抗、阿来替尼、布里加替尼、罗拉替尼和恩曲替尼，单独治疗ALK、EGFR和ROS1驱动的NSCLC大范围BrM病例（定义为>10个BrM或蛛网膜瘤病变）。所有BrMs均在研究入组、最佳中枢神经系统反应（最低点）和第一次中枢神经系统进展时被勾画。符合条件的患者共12例，其中6例为ALK，3例为EGFR，3例为ROS1驱动的NSCLC。在提出病例时，BrM的中位数数量和体积分别为49和19.6 cm3。11名患者（91.7%）通过经修改的RECIST标准对TKI首次治疗取得了中枢神经系统反应（10个部分反应，1个完全反应，1个稳定病体），最低点出现在中位数5.1个月。在最低点时，BrM的中位数数量和体积分别为5（每患者中位数减少91.7%）和0.3 cm3（每患者中位数减少96.5%）。11名患者（91.6%）在中枢神经系统进展时出现了随后的中枢神经系统进展（7个局部失败，3个局部+远程，1个远程），中位数为17.9个月。在中枢神经系统进展时，BrM的中位数数量和体积分别为7个和0.7 cm3。7名患者（58.3%）接受了拯救性SRS，没有患者接受拯救性WBRT。从治疗大范围BrM病例开始到总体生存中位数为43.2个月。在这个初步的病例系列中，我们描述了中枢神经系统降级作为一种有前途的多专业治疗模式，涉及中枢神经系统活性全身治疗和对广泛BrM的密切MRI监测，以避免先期WBRT并将某些患者转化为SRS候选者的策略。版权所有©2023 Elsevier B.V.。保留所有权利。

For extensive brain metastases (BrM) presentations arising from oncogene-addicted lung cancer, tyrosine kinase inhibitors (TKIs) with high response rates in the central nervous system (CNS) could potentially downstage the CNS disease burden, allowing for the avoidance of upfront whole-brain radiotherapy (WBRT) and the conversion of some patients into candidates for focal stereotactic radiosurgery (SRS).We describe the outcomes of patients with ALK, EGFR, and ROS1-driven NSCLC with extensive BrM presentations (defined as > 10 BrMs or leptomeningeal disease) treated with upfront newer generation CNS-active TKIs alone, including osimertinib, alectinib, brigatinib, lorlatinib, and entrectinib, from 2012 to 2021 at our institution. All BrMs were contoured at study entry, best CNS response (nadir), and first CNS progression.Twelve patients met criteria including 6 with ALK, 3 with EGFR, and 3 with ROS1-driven NSCLC. The median number and volume of BrMs at presentation were 49 and 19.6 cm3, respectively. Eleven patients (91.7 %) achieved a CNS response by modified-RECIST criteria to upfront TKI (10 partial responses, 1 complete response, 1 stable disease) with nadir observed at a median of 5.1 months. At nadir, the median number and volume of BrMs were 5 (median 91.7 % reduction per-patient) and 0.3 cm3(median 96.5 % reduction per-patient), respectively. Eleven patients (91.6 %) developed subsequent CNS progression (7 local failures, 3 local + distant, 1 distant) at a median of 17.9 months. At CNS progression, the median number and volume of BrMs were 7 and 0.7 cm3, respectively. Seven patients (58.3 %) received salvage SRS and no patients received salvage WBRT. The median overall survival from initiation of TKI for the extensive BrM presentation was 43.2 months.In this initial case series, we describeCNS downstagingas a promising multidisciplinary treatment paradigm involving the upfront administration CNS-active systemic therapy and close MRI surveillance for extensive BrMs as a strategy to avoid upfront WBRTand to convert some patients into SRS candidates.Copyright © 2023 Elsevier B.V. All rights reserved.