立体定向与无法修饰的放射疗法，用于无法手术的I期非小细胞肺癌：光泽3期随机临床试验

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加拿大中心。具有医学上无法手术I期（≤5cm）NSCLC的患者在4个分数（外围NSCLC）中为48 Gy的SBRT随机分配2：1，或在8个分数中的60 Gy中，与60 GY中的60 Gy在15个分数中的CRT中为60 Gy。从2014年5月到2020年1月收集了数据，并分析了2022年7月至2023年7月的数据。SBRT或CRT。主要目标是确定SBRT的有效性与基于LC 3年时的CRT相比。次要结果包括无事件的生存，整体生存和有毒作用。所有辐射计划均需进行实时/最终审查。局部故障进行了集中裁决。该研究旨在检测SBRT从75％提高到87.5％的3年LC。目标样本量为324例。233例患者，男性为119（51.1％），平均年龄为75.4（7.7）年；中值（IQR）随访时间为36.1（26.4-52.8）月。共有154名患者接受了SBRT，79例接受了CRT。 SBRT的3年LC为87.6％（95％CI，81.9％-93.4％），CRT的LC为81.2％（95％CI，71.9％-90.5％）（危险比[HR]，0.61; 95％CI，0.31-1.20; p = .15）。对于无事件存活率的HR为1.02（95％CI，0.72-1.45; p = .87），总体存活率为1.18（95％CI，0.80-1.76; P = .40）。观察到最小的急性毒性作用。在随机分配给SBRT的那些中，后期3或4级有毒作用发生在45个中央NSCLC中的5（11％）中，其中2个（11％）和109（1.8％）中有2个（1.8％），外围NSCLC。在随机分配给CRT的那些中，在19（5％）中有1个中央NSCLC和60（2％）中有1个（2％）。一名接受SBRT超中心病变（目标重叠近端支气管）的患者可能会发生与治疗相关的5级事件（heasoptysis）。该RCT将肺SBRT与包括中枢/超中性肿瘤的肺SBRT与肺部SBRT进行了比较。组之间的LC未检测到差异。严重的毒性作用受到限制，包括中枢肿瘤患者。该试验提供了评估SBRT的重要前瞻性数据；但是，对于确定SBRT对于外围和中央NSCLC.ClinicalTrials.gov标识符：NCT03924869是否比CRT更有效，需要进一步研究。

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.