ImportanceStereotactic 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.ObjectiveTo examine whether SBRT would improve local control (LC) compared with hypofractionated conventional radiotherapy (CRT).Design, Setting, and ParticipantsThis 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.InterventionsSBRT or CRT.Main Outcomes and MeasuresThe 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.ResultsOf 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).Conclusions and RelevanceThis 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.Trial RegistrationClinicalTrials.gov Identifier: NCT03924869

中文翻译：

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立体定向与大分割放疗治疗无法手术的 I 期非小细胞肺癌


重要性立体定向放射治疗 （SBRT） 广泛用于医学上不能手术的 I 期非小细胞肺癌 （NSCLC），但随机临床试验 （RCT） 的不同结果和对治疗中心性肿瘤的担忧仍然存在。目的探讨与大分割常规放疗 （CRT） 相比，SBRT 是否能改善局部控制 （LC）。设计、设置和参与者该 3 期 RCT 在加拿大 16 个中心进行。医学上不能手术的 I 期 （≤5 cm） NSCLC 患者以 2：1 的比例随机分配至 48 Gy 分 4 次 （外周 NSCLC） 或 60 Gy 分 8 次 （中枢性 NSCLC） 的 SBRT 与 60 Gy 分 15 次的 CRT。数据收集时间为 2014 年 5 月至 2020 年 1 月，数据分析时间为 2022 年 7 月至 2023 年 7 月。主要结局和测量主要目的是确定 SBRT 与基于 LC 的 CRT 相比在 3 年时的有效性。次要结局包括无事件生存期、总生存期和毒性作用。所有辐射计划都经过实时/最终审查。本地失败被集中裁决。该研究旨在检测 SBRT 的 3 年 LC 改善从 75% 到 87.5%。目标样本量为 324 名患者。结果在 233 例纳入的患者中，男性 119 例 （51.1%），平均 （SD） 年龄为 75.4 （7.7） 岁;中位 （IQR） 随访时间为 36.1 （26.4-52.8） 个月。共有 154 例患者接受了 SBRT，79 例接受了 CRT。SBRT 的 3 年 LC 为 87.6% （95% CI，81.9%-93.4%），CRT 为 81.2% （95% CI，71.9%-90.5%） （风险比 [HR]，0.61;95% CI，0.31-1.20;P = .15）。HR 为 1.02 （95% CI，0.72-1.45;P = .87） 对于无事件生存期和 1.18 （95% CI，0.80-1.76;P = .40） 的总生存期。观察到最小的急性毒性作用。 在随机接受 SBRT 的患者中，45 例中枢性 NSCLC 患者中有 5 例 （11%） 发生晚期 3 级或 4 级毒性作用，109 例中枢 NSCLC 患者中有 2 例 （1.8%） 发生晚期 3 级或 4 级毒性作用;在随机接受 CRT 的患者中，19 例中有 1 例 （5%） 患有中枢性 NSCLC，60 例中有 1 例 （2%） 患有外周 NSCLC。1 例因超中央病变 （目标重叠近端支气管） 接受 SBRT 的患者可能经历了与治疗相关的 5 级事件 （咯血）。结论和相关性该 RCT 比较了肺 SBRT 与包括中枢/超中枢肿瘤的大分割 CRT。组间 LC 未检测到差异。严重的毒性作用是有限的，包括患有中央肿瘤的患者。该试验提供了评估 SBRT 的重要前瞻性数据;然而，需要进一步的研究来确定 SBRT 是否比 CRT 对外周和中枢 NSCLC 更有效。试验注册临床试验。gov 标识符： NCT03924869