IMPORTANCE Evidence is lacking from randomized clinical trials to guide the optimal approach for stereotactic ablative body radiotherapy (SABR) in patients with pulmonary oligometastases. OBJECTIVE To assess whether single-fraction or multifraction SABR is more effective for the treatment of patients with pulmonary oligometastases. DESIGN, SETTING, AND PARTICIPANTS This multicenter, unblinded, phase 2 randomized clinical trial of 90 patients across 13 centers in Australia and New Zealand enrolled patients with 1 to 3 lung oligometastases less than or equal to 5 cm from any nonhematologic malignant tumors located away from the central airways, Eastern Cooperative Oncology Group performance status 0 or 1, and all primary and extrathoracic disease controlled with local therapy. Enrollment was from January 1, 2015, to December 31, 2018, with a minimum patient follow-up of 2 years. INTERVENTIONS Single fraction of 28 Gy (single-fraction arm) or 4 fractions of 12 Gy (multifraction arm) to each oligometastasis. MAIN OUTCOMES AND MEASURES The main outcome was grade 3 or higher treatment-related adverse events (AEs) occurring within 1 year of SABR. Secondary outcomes were freedom from local failure, overall survival, disease-free survival, and patient-reported outcomes (MD Anderson Symptom Inventory-Lung Cancer and EuroQol 5-dimension visual analog scale). RESULTS Ninety participants were randomized, of whom 87 were treated for 133 pulmonary oligometastases. The mean (SD) age was 66.6 [11.6] years; 58 (64%) were male. Median follow-up was 36.5 months (interquartile range, 24.8-43.9 months). The numbers of grade 3 or higher AEs related to treatment at 1 year were 2 (5%; 80% CI, 1%-13%) in the single-fraction arm and 1 (3%; 80% CI, 0%-10%) in the multifraction arm, with no significant difference observed between arms. One grade 5 AE occurred in the multifraction arm. No significant differences were found between the multifraction arm and single-fraction arm for freedom from local failure (hazard ratio [HR], 0.5; 95% CI, 0.2-1.3; P = .13), overall survival (HR, 1.5; 95% CI, 0.6-3.7; P = .44), or disease-free survival (HR, 1.0; 95% CI, 0.6-1.6; P > .99). There were no significant differences observed in patient-reported outcomes. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, neither arm demonstrated evidence of superior safety, efficacy, or symptom burden; however, single-fraction SABR is more efficient to deliver. Therefore, single-fraction SABR, as assessed by the most acceptable outcome profile from all end points, could be chosen to escalate to future studies. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01965223.

中文翻译：

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肺寡转移瘤的单次与多次立体定向消融体放射治疗 (SAFRON II)：跨塔斯曼放射肿瘤学组 13.01 期 2 期随机临床试验。

重要性 随机临床试验缺乏证据来指导肺寡转移患者立体定向消融体放射治疗 (SABR) 的最佳方法。目的 评估单次或多次 SABR 对肺寡转移患者的治疗是否更有效。设计、地点和参与者 这项多中心、非盲法、2 期随机临床试验在澳大利亚和新西兰的 13 个中心对 90 名患者进行了纳入，其中 1 至 3 处肺寡转移灶距离任何非血液系统恶性肿瘤的距离小于或等于 5 cm。中央气道，东部肿瘤协作组体力状态 0 或 1，所有原发性和胸外疾病均通过局部治疗得到控制。报名时间为 2015 年 1 月 1 日至 2018 年 12 月 31 日，至少对患者进行 2 年的随访。干预 28 Gy 的单次分割（单分割臂）或 12 Gy 的 4 分割（多分割臂）到每个寡转移灶。主要结果和措施 主要结果是 SABR 后 1 年内发生的 3 级或更高级别的治疗相关不良事件 (AE)。次要结局是免于局部失败、总生存期、无病生存期和患者报告的结局（MD Anderson Symptom Inventory-Lung Cancer 和 EuroQol 5 维视觉模拟量表）。结果 90 名参与者被随机分配，其中 87 人接受了 133 例肺寡转移瘤的治疗。平均 (SD) 年龄为 66.6 [11.6] 岁；58 人（64%）为男性。中位随访时间为 36.5 个月（四分位距，24.8-43.9 个月）。1 年时与治疗相关的 3 级或更高 AE 数量为 2（5%；80% CI，1%-13%）单次分割组和 1 个（3%；80% CI，0%-10%）在多分割组中，两组之间没有观察到显着差异。多分次治疗组发生 1 次 5 级 AE。在免于局部失败（风险比 [HR]，0.5；95% CI，0.2-1.3；P = 0.13）、总生存期（HR，1.5；95 % CI，0.6-3.7；P = .44）或无病生存期（HR，1.0；95% CI，0.6-1.6；P > .99）。在患者报告的结果中没有观察到显着差异。结论和相关性 在这项随机临床试验中，两组均未显示出优越的安全性、有效性或症状负担的证据。但是，单组分 SABR 的交付效率更高。因此，单组分 SABR，根据所有终点的最可接受的结果概况评估，可以选择升级到未来的研究。试验注册 ClinicalTrials.gov 标识符：NCT01965223。