BACKGROUND Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation. METHODS We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181. FINDINGS Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group. INTERPRETATION APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women. FUNDING National Cancer Institute, US Department of Health and Human Services.

中文翻译：

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早期乳腺癌保乳手术后加速部分乳房照射的长期主要结果：一项随机、3 期、等效试验。

背景 早期乳腺癌患者保乳手术后全乳放疗可减少同侧乳腺肿瘤复发 (IBTR)，产生与乳房切除术相当的结果。目前尚不清楚加速部分乳房照射 (APBI) 是否仅对荷瘤象限（缩短治疗时间）同样有效。在我们的试验中，我们调查了与全乳放疗相比，APBI 是否在肿块切除术后提供了等效的局部肿瘤控制。方法 我们在美国、加拿大、爱尔兰和以色列的 154 个临床中心进行了这项随机的 3 期等效试验 (NSABP B-39/RTOG 0413)。成年女性（>18 岁）患有早期（0、I 或 II；无远处转移证据，但最多三个腋窝淋巴结可为阳性）乳腺癌（肿瘤大小≤3 cm；包括所有组织学和多灶性乳腺癌），使用基于偏差硬币的最小化算法随机分配（1：1）接受乳房切除术且手术切缘阴性（即未检测到癌细胞）的患者接受全乳照射（全乳照射组）或 APBI（APBI 组）。全乳照射在 5 周内以 50 Gy 的每日 25 次分次进行，有或没有对肿瘤床进行补充推量，APBI 以 34 Gy 的近距离放射治疗或 38·5 Gy 的外照射放疗分 10 次进行, 在 8 天内超过 5 个治疗日。随机分组按疾病分期、绝经状态、激素受体状态和接受化疗的意向进行分层。患者、研究人员和统计学家不能对治疗分配设盲。在意向治疗人群中分析了作为首次复发的侵入性和非侵入性 IBTR 的主要结果，排除了那些失访的患者，并基于 50% 的边际增加进行了等效性检验风险比（观察到的 HR 在 0·667 和 1·5 之间的等效性的 90% CI）和 Cox 比例风险模型。通过意向性治疗评估生存期，并在符合方案人群中进行敏感性分析。该试验已在 ClinicalTrials.gov 注册，NCT00103181。调查结果 2005 年 3 月 21 日至 2013 年 4 月 16 日期间，共有 4216 名女性入组。2109 人被分配到全乳照射组，2107 人被分配到 APBI 组。全乳照射组 70 例患者和 APBI 组 14 例患者在此阶段撤回同意或失访，因此分别有 2039 和 2093 名患者可用于生存分析。此外，分别有 3 名和 4 名患者失去临床随访（即通过电话评估生存状态但未进行身体检查），留下全乳照射组 2036 名患者和 APBI 组 2089 名患者可评估主要结果。中位随访 10·2 年 (IQR 7·5-11·5)，APBI 组 2089 名女性中有 90 名 (4%) 符合主要结局，2036 名女性中有 71 名 (3%)全乳照射组的 IBTR (HR 1·22, 90% CI 0·94-1·58)。APBI 组 IBTR 的 10 年累积发生率为 4·6%（95% CI 3·7-5·7），而全乳照射组为 3·9%（3·1-5·0） . 全乳放疗组 2039 名患者中的 44 名 (2%) 和 APBI 组 2093 名患者中的 49 名 (2%) 死于复发性乳腺癌。没有与治疗相关的死亡。两组之间的第二癌症和治疗相关毒性相似。全乳照射组 2020 名患者和 APBI 组 2089 名患者有不良事件的可用数据。报告的最高毒性等级为：APBI 组 845 名 (40%) 患者为 1 级，921 名 (44%) 患者为 2 级，201 名 (10%) 患者为 3 级，而 626 名 (31%) 患者为 1 级, 全乳照射组 1193 例 (59%) 为 2 级，143 例 (7%) 为 3 级。解释 APBI 在控制保乳治疗的 IBTR 方面不符合与全乳照射等效的标准。我们的试验有广泛的资格标准，导致大量的，异质性患者库和足够的能力来检测治疗等效性，但并非旨在测试患者亚组的等效性或不同 APBI 技术的结果。对于早期乳腺癌患者，我们的研究结果支持乳房肿瘤切除术后的全乳放疗；然而，由于 IBTR 的 10 年累积发生率的绝对差异小于 1%，因此 APBI 可能是某些女性可以接受的替代方案。资助美国卫生与公共服务部国家癌症研究所。由于 IBTR 的 10 年累积发生率的绝对差异小于 1%，APBI 可能是某些女性可以接受的替代方案。资助美国卫生与公共服务部国家癌症研究所。由于 IBTR 的 10 年累积发生率的绝对差异小于 1%，APBI 可能是某些女性可以接受的替代方案。资助美国卫生与公共服务部国家癌症研究所。