不可手术的I期非小细胞肺癌（NSCLC）第3期LUSTRE随机临床试验：立体定向放疗（SBRT）与高分次放疗（Hypofractionated Radiotherapy, CRT）比较

立体定向体部放疗（SBRT）广泛用于中期无法手术治疗的Ⅰ期非小细胞肺癌（NSCLC），但不同随机临床试验（RCT）结果不一，且在治疗中心位肿瘤时仍存在担忧。旨在评估SBRT是否能改善局部控制（LC），相较于常规高分次放疗（CRT）。这是在加拿大16个中心开展的第3阶段RCT。符合条件的非手术治疗的Ⅰ期（≤5 cm）NSCLC患者被随机2:1分配到：SBRT（外围肿瘤为48 Gy，4次分次）或（中心肿瘤为60 Gy，8次分次）与传统CRT（60 Gy，15次分次）组。数据收集时间为2014年5月至2020年1月，分析截止至2023年7月。主要比较各组在3年局部控制（LC）方面的效果。次要结局包括无事件生存（EFS）、总生存（OS）及毒副作用。所有放疗计划均经过实时/最终评审，局部失败由中心评审确认。设计目标是检测SBRT在3年LC由75%提升至87.5%的效果，目标样本量为324例。最终入选的233例患者中，男性119例（51.1%），年龄中位数（SD）为75.4（7.7）岁，随访中位数（IQR）为36.1（26.4-52.8）个月。154例接受SBRT，79例接受CRT。3年LC分别为87.6%（95% CI，81.9%-93.4%）和81.2%（95% CI，71.9%-90.5%），差异无统计学意义（HR=0.61，95% CI，0.31-1.20，P=0.15）。EFS和OS的HR分别为1.02（95% CI，0.72-1.45，P=0.87）和1.18（95% CI，0.80-1.76，P=0.40），差异均无显著。两组间短期毒副作用有限。SBRT组中，晚期3或4级毒副作用在中心肿瘤患者为11%（5/45），外围肿瘤为1.8%（2/109）；CRT组中，中心肿瘤为5%（1/19），外围为2%（1/60）。一例接受SBRT治疗的超中心肿瘤（邻近支气管）患者发生可能与治疗相关的5级事件（咯血）。本研究对SBRT在治疗中枢/超中枢肿瘤中的应用提供了重要前瞻性数据，但仍需进一步研究以确定SBRT相较于CRT在外围及中枢NSCLC中的优势。临床试验注册号：NCT03924869。

Stereotactic body radiotherapy (SBRT) is widely used for stage I medically inoperable non-small cell lung cancer (NSCLC), yet varied results from randomized clinical trials (RCTs) and concerns in treating centrally located tumors persist.To examine whether SBRT would improve local control (LC) compared with hypofractionated conventional radiotherapy (CRT).This phase 3 RCT was conducted in 16 Canadian centers. Patients with medically inoperable stage I (≤5 cm) NSCLC were randomized 2:1 to SBRT of 48 Gy in 4 fractions (peripheral NSCLC) or 60 Gy in 8 fractions (central NSCLC) vs CRT of 60 Gy in 15 fractions. Data were collected from May 2014 to January 2020, and data were analyzed from July 2022 to July 2023.SBRT or CRT.The primary objective was to determine the effectiveness of SBRT compared with CRT based on LC at 3 years. Secondary outcomes included event-free survival, overall survival, and toxic effects. All radiation plans were subject to real-time/final review. Local failures were centrally adjudicated. The study was designed to detect a 3-year LC improvement of SBRT from 75% to 87.5%. The target sample size was 324 patients.Of 233 included patients, 119 (51.1%) were male, and the mean (SD) age was 75.4 (7.7) years; the median (IQR) follow-up was 36.1 (26.4-52.8) months. A total of 154 patients received SBRT and 79 received CRT. The 3-year LC was 87.6% (95% CI, 81.9%-93.4%) for SBRT and 81.2% (95% CI, 71.9%-90.5%) for CRT (hazard ratio [HR], 0.61; 95% CI, 0.31-1.20; P = .15). The HR was 1.02 (95% CI, 0.72-1.45; P = .87) for event-free survival and 1.18 (95% CI, 0.80-1.76; P = .40) for overall survival. Minimal acute toxic effects were observed. Among those randomized to SBRT, late grade 3 or 4 toxic effects occurred in 5 of 45 (11%) with central NSCLC and 2 of 109 (1.8%) with peripheral NSCLC; among those randomized to CRT, in 1 of 19 (5%) with central NSCLC and 1 of 60 (2%) with peripheral NSCLC. One patient who received SBRT for an ultracentral lesion (target overlapping proximal bronchus) experienced a possible treatment-related grade 5 event (hemoptysis).This RCT compared lung SBRT with hypofractionated CRT that included central/ultracentral tumors. No difference was detected in LC between groups. Severe toxic effects were limited, including patients with central tumors. The trial provides important prospective data evaluating SBRT; however, further research is necessary to determine if SBRT is more effective than CRT for peripheral and central NSCLC.ClinicalTrials.gov Identifier: NCT03924869.