Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 10-year efficacy and late normal tissue effects from a multicentre, open-label, non-inferiority, phase 3, randomised controlled trial and 5-year efficacy results from a randomised axillary substudy.

Primary analysis showed non-inferiority of 5-year ipsilateral breast recurrence for 26 Gy and 27 Gy in five fractions over 1 week, with 26 Gy also having similar results to 40 Gy for normal tissue effects.

主要分析显示，对于1周内5次分割的26 Gy和27 Gy，5年同侧乳腺复发率不劣于标准方案，且26 Gy对正常组织的影响与40 Gy相似。

Here, we report 10-year outcomes of the FAST-Forward trial and 5-year efficacy outcomes of a substudy assessing the approach in patients requiring axillary treatment.

在这里，我们报告了FAST-Forward试验的10年结果和一个子研究的5年疗效结果，该子研究评估了需要腋窝治疗的患者的治疗方案。

Methods

FAST-Forward is a multicentre, open-label, non-inferiority, phase 3, randomised controlled trialdone at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK.

FAST-Forward是一项多中心、开放标签、非劣效性、第三阶段、随机对照试验，在英国的97家医院（47家放射治疗中心和50家转诊医院）进行。

Patients aged 18 years or older with invasive carcinoma of the breast (pT1-3, pN0-1, M0) after breast conservation surgery or mastectomy were eligible.

年龄在18岁或以上的侵袭性乳腺癌患者（pT1-3，pN0-1，M0）在进行乳房保留手术或乳房切除术后符合资格。

We randomly allocated patients (in a 1:1:1 ratio with random permuted blocks, stratified by radiotherapy centre) to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall.

我们以1:1:1的比例，使用随机排列的分块方法（按放疗中心分层），将患者随机分配到以下三种治疗方案之一：全乳或胸壁接受40 Gy/15次（3周内完成）、27 Gy/5次（1周内完成）或26 Gy/5次（1周内完成）。

Allocation was not masked because of the nature of the intervention.

由于干预措施的性质，未对分配进行盲法处理。

The primary endpoint was non-inferiority of ipsilateral breast recurrence at 5 years.

主要终点是5年内同侧乳腺复发的非劣效性。

Here, we report the planned 10-year analysis assessed in the intention-to-treatpopulation (all participants who were randomly assigned and consented for use of data).

在这里，我们报告了在意向治疗人群中计划进行的10年分析（所有被随机分配并同意使用数据的参与者）。

We also report a planned intention-to-treatanalysis of a subsequent substudy assessing 5-year efficacy of the same schedules in patients meeting the study criteria but requiring axillary treatment.

我们还报告了随后的子研究的计划意向治疗分析，该研究评估了符合研究标准但需要腋窝治疗的患者在相同方案下5年的疗效。

The clinical trial was registered with ISRCTN (ISRCTN19906132); the main trial is complete, follow-up of the substudy cohort is ongoing.

该临床试验已在ISRCTN注册（ISRCTN19906132）；主要试验已完成，随访研究队列正在进行中。

Results

Between Nov 24, 2011, and June 19, 2014, 4110 participants were enrolled in the main FAST-Forward trial. 23 withdrew consent for data use and were excluded and 4087 participants were included in the intention-to-treatpopulation for this 10-year analysis.

2011年11月24日至2014年6月19日期间，共有4110名参与者被纳入主要的FAST-Forward试验。其中23人撤回了数据使用同意，被排除在外，因此本10年分析的意向治疗人群中包括了4087名参与者。

Participants were randomly assigned to 40 Gy (n=1358), 27 Gy (n=1362), or 26 Gy (n=1367).

参与者被随机分配到40 Gy (n=1358), 27 Gy (n=1362), 或 26 Gy (n=1367)组。

Median follow-up was 10·1 years (IQR 10·0-10·2).

中位随访时间为10.1年（四分位数间距10.0-10.2）。

Ipsilateral breast recurrence was reported for 116 participants (45 in the 40 Gy group, 41 in the 27 Gy group, and 30 in the 26 Gy group), with 10-year cumulative incidenceof 3·6% (95% CI 2·7-4·9) for the 40 Gy group, 2·9% (2·1-4·0) for the 27 Gy group, and 2·1% (1·5-3·1) for the 26 Gy group. 10-year clinician-reported moderate or marked breast or chest wall effects occurred in 100 (13·1%) of 765 participants in the 40 Gy group, 157 (19·3%) of 814 in the 27 Gy group, and 111 (14·4%) of 770 in the 26 Gy group.

在116名参与者中报告了同侧乳腺复发（40 Gy组45人，27 Gy组41人，26 Gy组30人），40 Gy组的10年累积发生率为3.6%（95%置信区间2.7-4.9），27 Gy组为2.9%（2.1-4.0），26 Gy组为2.1%（1.5-3.1）。在40 Gy组的765名参与者中，有100名（13.1%）在10年内出现临床医生报告的中度或显著的乳腺或胸壁影响，27 Gy组的814名中有157名（19.3%），26 Gy组的770名中有111名（14.4%）。

Between April 11, 2016, and Oct 2, 2018, 469 participants enrolled in the nodal substudy, 466 of which were included in intention-to-treatanalyses.

2016年4月11日至2018年10月2日期间，共有469名参与者加入淋巴结亚研究，其中466名被纳入意向治疗分析。

Median follow-up was 7·0 years (IQR 6·2-7·1) and 32 locoregional recurrences were reported.

中位随访时间为7.0年（四分位数间距6.2-7.1年），报告了32例局部区域复发。

interpretation

Long-term follow-up confirms that 26 Gy in five fractions over 1 week is safe and efficacious for adjuvant radiotherapy to the breast or chest wall, supporting its use as a standard of care.

长期随访证实，每周1周内分5次给予26 Gy的剂量进行乳腺或胸壁辅助放疗是安全且有效的，支持将其作为标准治疗。

Efficacy data for this schedule in the axillary nodal radiotherapy setting are reassuring; however, sample size limits precision of estimation for this subgroup on its own.

该方案在腋窝淋巴结放疗环境中的疗效数据令人放心；但是，样本量限制了仅对这一亚组进行估计的精确性。

funding

UK National Institute for Health and Care Research.

英国国家卫生与护理研究院