Zheng Shiyang, Ding Shouliang, Liu Biaoshui, Xiong Yixin, Zhou Rui, Zhang Pengxin, Liu Fangjie, Liu Yimei, Chen Meining, Situ Yu, Wang Mengru, Huang Xiaoyan, Yin Shaohan, Fang Wenfeng, Mou Yonggao, Qiu Bo, Wang Daquan, Liu Hui
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
EClinicalMedicine. 2025 Apr 9;82:103189. doi: 10.1016/j.eclinm.2025.103189. eCollection 2025 Apr.
Brain metastases (BMs) in non-small cell lung cancer (NSCLC) are associated with poor prognosis and quality of life (QoL). This study aimed to evaluate the efficacy and safety of online adaptive MR-guided fractionated stereotactic radiotherapy (FSRT) using a 1.5 T MR-Linac in this subgroup of patients.
This single-arm phase 2 trial was conducted at Sun Yat-sen University Cancer Centre. Patients aged 18-75 years with NSCLC, 1-10 BMs, and an ECOG status of 0-1 were included. Key exclusion criteria included inability to undergo contrast-enhanced MRI and contraindications to bevacizumab. Patients received 30 Gy adaptive FSRT in 5 daily fractions under real-time MR guidance, with bevacizumab before (day 1) and after (day 21) FSRT. The primary endpoint was 1-year intracranial progression-free survival (IPFS); secondary endpoints included objective response rate (ORR), 1-year progression-free survival (PFS), 1-year overall survival (OS), treatment-related toxicities, and QoL. All enrolled patients were included in primary and safety analyses. This trial is registered with Clinicaltrials.gov, NCT04946019.
Between June 10th, 2021 and June 29th, 2023, 70 patients were assessed for eligibility and 55 patients were enrolled (median follow-up: 22.3 months). The median age was 58 years (IQR: 51-65), with 33% (18/55) female patients, and 82% (45/55) presenting with adenocarcinoma. The 1-year IPFS rate was 78.7% (95% CI, 68.2%-90.7%), with a median IPFS of 21.9 months (95% CI, 13.8-30.1 months). The 1-year PFS rate was 63.5% (95% CI: 51.8%-78.2%), and OS was 82.4% (95% CI: 72.6%-93.6%). The ORR reached 78% (95% CI: 65.0%-88.2%). Treatment-related toxicity was minimal, with only one case (2%) of grade 1 radiation necrosis. QoL improved steadily, with the Global Health Status score increasing from 65.67 ± 16.97 to 79.33 ± 8.79 at 6 months post FSRT (p < 0.0001).
Online adaptive FSRT using a 1.5 T MR-Linac has demonstrated effectiveness and good tolerability for BMs in patients with NSCLC. However, the relatively small sample size and short follow-up may affect result generalizability. Further randomised studies are warranted to confirm these findings and establish optimal treatment protocols.
The National Natural Science Foundation of China (Grant Number 82073328).
非小细胞肺癌（NSCLC）脑转移（BMs）与预后不良和生活质量（QoL）相关。本研究旨在评估在该亚组患者中使用1.5T MR直线加速器进行在线自适应磁共振引导的分次立体定向放射治疗（FSRT）的疗效和安全性。
本单臂2期试验在中山大学肿瘤防治中心进行。纳入年龄在18 - 75岁、患有NSCLC、有1 - 10个脑转移灶且东部肿瘤协作组（ECOG）状态为0 - 1的患者。主要排除标准包括无法进行增强磁共振成像（MRI）以及对贝伐单抗有禁忌证。患者在实时磁共振引导下接受30Gy的自适应FSRT，分5次每日照射，在FSRT前（第1天）和后（第21天）使用贝伐单抗。主要终点是1年颅内无进展生存期（IPFS）；次要终点包括客观缓解率（ORR）、1年无进展生存期（PFS）、1年总生存期（OS）、治疗相关毒性和生活质量。所有入组患者均纳入主要分析和安全性分析。本试验已在Clinicaltrials.gov注册，注册号为NCT04946019。
在2021年6月10日至2023年6月29日期间，评估了70例患者的 eligibility，55例患者入组（中位随访时间：22.3个月）。中位年龄为58岁（四分位间距：51 - 65岁），女性患者占33%（18/55），82%（45/55）为腺癌。1年IPFS率为78.7%（95%置信区间，68.2% - 90.7%），中位IPFS为21.9个月（95%置信区间，13.8 - 30.1个月）。1年PFS率为63.5%（95%置信区间：51.8% - 78.2%），OS为82.4%（95%置信区间：72.6% - 93.6%）。ORR达到78%（95%置信区间：65.0% - 88.2%）。治疗相关毒性极小，仅1例（2%）1级放射性坏死。生活质量稳步改善，FSRT后6个月时全球健康状况评分从65.67 ± 16.97提高到79.33 ± 8.79（p < 0.0001）。
使用1.5T MR直线加速器进行在线自适应FSRT已证明对NSCLC患者的脑转移有效且耐受性良好。然而，样本量相对较小和随访时间较短可能会影响结果的普遍性。有必要进行进一步的随机研究以证实这些发现并建立最佳治疗方案。
中国国家自然科学基金（批准号82073328）。
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