IMPORTANCE A significant subset of patients with stage II/III non-small cell lung cancer (NSCLC) cannot receive standard concurrent chemoradiotherapy owing to the risk of toxic effects outweighing potential benefits. Without concurrent chemotherapy, however, the efficacy of conventional radiotherapy is reduced. OBJECTIVE To determine whether hypofractionated image-guided radiotherapy (IGRT) would improve overall survival in patients with stage II/III NSCLC who could not receive concurrent chemoradiotherapy and therefore were traditionally relegated to receiving only conventionally fractionated radiotherapy (CFRT). DESIGN, SETTING, AND PARTICIPANTS This nonblinded, phase 3 randomized clinical study enrolled 103 patients and analyzed 96 patients with stage II/III NSCLC and Zubrod performance status of at least 2, with greater than 10% weight loss in the previous 6 months, and/or who were ineligible for concurrent chemoradiotherapy after oncology consultation. Enrollment occurred at multiple US institutions. Patients were enrolled from November 13, 2012, to August 28, 2018, with a median follow-up of 8.7 (3.6-19.9) months. Data were analyzed from September 14, 2018, to April 11, 2021. INTERVENTIONS Eligible patients were randomized to hypofractionated IGRT (60 Gy in 15 fractions) vs CFRT (60 Gy in 30 fractions). MAIN OUTCOMES AND MEASURES The primary end point was 1-year overall survival. RESULTS A total of 103 patients (96 of whom were analyzed [63 men (65.6%); mean (SD) age, 71.0 (10.2) years (range, 50-90 years)]) were randomized to hypofractionated IGRT (n = 50) or CFRT (n = 46) when a planned interim analysis suggested futility in reaching the primary end point, and the study was closed to further accrual. There was no statistically significant difference between the treatment groups for 1-year overall survival (37.7% [95% CI, 24.2%-51.0%] for hypofractionated IGRT vs 44.6% [95% CI, 29.9%-58.3%] for CFRT; P = .29). There were also no significant differences in median overall survival, progression-free survival, time to local failure, time to distant metastasis, and toxic effects of grade 3 or greater between the 2 treatment groups. CONCLUSIONS AND RELEVANCE This phase 3 randomized clinical trial found that hypofractionated IGRT (60 Gy in 15 fractions) was not superior to CFRT (60 Gy in 30 fractions) for patients with stage II/III NSCLC ineligible for concurrent chemoradiotherapy. Further studies are needed to verify equivalence between these radiotherapy regimens. Regardless, for well-selected patients with NSCLC (ie, peripheral primary tumors and limited mediastinal/hilar adenopathy), the convenience of hypofractionated radiotherapy regimens may offer an appropriate treatment option. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01459497.

中文翻译：

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II/III 期非小细胞肺癌和体能状态不佳患者的加速大分割影像引导与常规放射治疗：一项随机临床试验。

重要性 有很大一部分 II/III 期非小细胞肺癌 (NSCLC) 患者不能接受标准同步放化疗，因为毒性作用的风险超过了潜在的益处。然而，如果没有同步化疗，传统放疗的疗效就会降低。目的 确定大分割影像引导放疗 (IGRT) 是否会提高无法接受同步放化疗的 II/III 期 NSCLC 患者的总体生存率，因此传统上只能接受常规分割放疗 (CFRT)。设计、设置和参与者 这项非盲、3 期随机临床研究招募了 103 名患者，分析了 96 名 II/III 期 NSCLC 患者，Zubrod 体能状态至少为 2，在过去 6 个月内体重减轻超过 10%，和/或在肿瘤科会诊后不适合同步放化疗。注册发生在多个美国机构。患者于 2012 年 11 月 13 日至 2018 年 8 月 28 日入组，中位随访时间为 8.7（3.6-19.9）个月。对 2018 年 9 月 14 日至 2021 年 4 月 11 日的数据进行了分析。干预 符合条件的患者被随机分配接受大分割 IGRT（60 Gy，15 次）与 CFRT（60 Gy，30 次）。主要结果和测量 主要终点是 1 年总生存期。结果 共有 103 名患者（其中 96 名进行了分析 [63 名男性（65.6%）；平均（SD）年龄，71.0（10.2）岁（范围，50-90 岁)]) 被随机分配到大分割 IGRT (n = 50) 或 CFRT (n = 46)，当时计划的中期分析表明达到主要终点无效，并且该研究已关闭以进一步招募。治疗组之间的 1 年总生存率无统计学差异（大分割 IGRT 为 37.7% [95% CI, 24.2%-51.0%]，而 CFRT 为 44.6% [95% CI, 29.9%-58.3%]； P = .29)。两个治疗组的中位总生存期、无进展生存期、局部失败时间、远处转移时间和 3 级或更高级别的毒性作用也没有显着差异。结论和相关性 该 3 期随机临床试验发现，对于不适合同步放化疗的 II/III 期 NSCLC 患者，大分割 IGRT（60 Gy，15 次分割）并不优于 CFRT（60 Gy，30 次分割）。需要进一步的研究来验证这些放射治疗方案之间的等效性。无论如何，对于精心挑选的 NSCLC 患者（即外周原发性肿瘤和有限的纵隔/肺门淋巴结肿大），大分割放疗方案的便利性可能提供适当的治疗选择。试验注册 ClinicalTrials.gov 标识符：NCT01459497。外周原发性肿瘤和有限的纵隔/肺门淋巴结肿大），大分割放射治疗方案的便利性可能提供适当的治疗选择。试验注册 ClinicalTrials.gov 标识符：NCT01459497。外周原发性肿瘤和有限的纵隔/肺门淋巴结肿大），大分割放射治疗方案的便利性可能提供适当的治疗选择。试验注册 ClinicalTrials.gov 标识符：NCT01459497。