Department of Oncology, McMaster University, and the Division of Radiation Oncology Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario, Canada.
Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
JAMA Oncol. 2024 Nov;10(11):1571-1575. doi: 10.1001/jamaoncol.2024.3089. Epub 2024 Sep 19.
IMPORTANCE: 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. OBJECTIVE: To examine whether SBRT would improve local control (LC) compared with hypofractionated conventional radiotherapy (CRT). DESIGN SETTING AND PARTICIPANTS: 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. INTERVENTIONS: SBRT or CRT. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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; = .15). The HR was 1.02 (95% CI, 0.72-1.45; = .87) for event-free survival and 1.18 (95% CI, 0.80-1.76; = .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 RELEVANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03924869.
重要性:立体定向体放射治疗(SBRT)广泛用于不能手术的 I 期非小细胞肺癌(NSCLC),但随机临床试验(RCT)的结果存在差异,且治疗中央型肿瘤的相关担忧仍存在。
目的:研究 SBRT 是否比低分割常规放疗(CRT)更能改善局部控制(LC)。
设计、地点和参与者:这是一项在加拿大 16 个中心进行的 3 期 RCT。不能手术的 I 期(≤5cm)非小细胞肺癌患者随机分为 2:1 组,分别接受 SBRT(外周型 NSCLC 为 48Gy 分 4 次,中央型 NSCLC 为 60Gy 分 8 次)或 CRT(60Gy 分 15 次)。数据于 2014 年 5 月至 2020 年 1 月收集,2022 年 7 月至 2023 年 7 月进行分析。
干预措施:SBRT 或 CRT。
主要观察指标:主要终点是基于 3 年 LC 确定 SBRT 与 CRT 的有效性。次要结果包括无事件生存、总生存和毒性作用。所有放射治疗计划都要经过实时/最终审查。局部失败由中央机构进行裁决。该研究旨在检测 SBRT 的 3 年 LC 从 75%提高到 87.5%。目标样本量为 324 例患者。
结果:在纳入的 233 例患者中,119 例(51.1%)为男性,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。154 例患者接受 SBRT,79 例接受 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%)(HR,0.61;95%CI,0.31-1.20; = 0.15)。无事件生存的 HR 为 1.02(95%CI,0.72-1.45; = 0.87),总生存的 HR 为 1.18(95%CI,0.80-1.76; = 0.40)。急性毒性作用轻微。随机分配到 SBRT 的患者中,5 例(11%)中央型 NSCLC 和 2 例(1.8%)外周型 NSCLC 发生 3 级或 4 级迟发性毒性作用;随机分配到 CRT 的患者中,1 例(5%)中央型 NSCLC 和 1 例(2%)外周型 NSCLC 发生 3 级或 4 级迟发性毒性作用。1 例接受 SBRT 治疗超中央病变(靶区重叠近端支气管)的患者出现可能与治疗相关的 5 级事件(咯血)。
结论和相关性:这项 RCT 比较了包括中央/超中央肿瘤的肺 SBRT 与低分割 CRT。两组间 LC 无差异。严重的毒性作用是有限的,包括中央型肿瘤的患者。该试验提供了重要的前瞻性数据,评估了 SBRT;然而,需要进一步的研究来确定 SBRT 是否比 CRT 更有效治疗外周型和中央型 NSCLC。
试验注册:ClinicalTrials.gov 标识符:NCT03924869。
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