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Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial.
The Lancet ( IF 98.4 ) Pub Date : 2020-04-28 , DOI: 10.1016/s0140-6736(20)30932-6
Adrian Murray Brunt 1 , Joanne S Haviland 2 , Duncan A Wheatley 3 , Mark A Sydenham 2 , Abdulla Alhasso 4 , David J Bloomfield 5 , Charlie Chan 6 , Mark Churn 7 , Susan Cleator 8 , Charlotte E Coles 9 , Andrew Goodman 10 , Adrian Harnett 11 , Penelope Hopwood 2 , Anna M Kirby 12 , Cliona C Kirwan 13 , Carolyn Morris 14 , Zohal Nabi 15 , Elinor Sawyer 16 , Navita Somaiah 12 , Liba Stones 2 , Isabel Syndikus 17 , Judith M Bliss 2 , John R Yarnold 12 ,
Affiliation  

Background

We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial.

Methods

FAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1–3, pN0–1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients 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. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1·6% excess for five-fraction schedules (critical hazard ratio [HR] of 1·81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132.

Findings

Between Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71·5 months (IQR 71·3 to 71·7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0·86 (95% CI 0·51 to 1·44) for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2·1% (1·4 to 3·1); estimated absolute differences versus 40 Gy in 15 fractions were −0·3% (−1·0 to 0·9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior five-fraction schedule: p=0·0022 vs 40 Gy in 15 fractions) and −0·7% (−1·3 to 0·3) for 26 Gy in five fractions (p=0·00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9·9%) 40 Gy patients, 155 (15·4%) of 1005 27 Gy patients, and 121 of 1020 (11·9%) 26 Gy patients. Across all clinician assessments from 1–5 years, odds ratios versus 40 Gy in 15 fractions were 1·55 (95% CI 1·32 to 1·83, p<0·0001) for 27 Gy in five fractions and 1·12 (0·94 to 1·34, p=0·20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy.

Interpretation

26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer.

Funding

National Institute for Health Research Health Technology Assessment Programme.



中文翻译:


1 周与 3 周的大分割乳房放疗(快进):5 年疗效和晚期正常组织效应来自多中心、非劣效性、随机、3 期试验。


 背景


我们的目标是确定 1 周内实施的 5 次辅助放疗(放射治疗)方案,该方案在局部癌症控制方面不逊色,并且与早期乳腺癌初次手术后国际标准 15 次方案一样安全。在此,我们展示 FAST-Forward 试验的 5 年结果。

 方法


FAST-Forward 是一项在英国 97 家医院(47 家放射治疗中心和 50 家转诊医院)进行的多中心、3 期、随机、非劣效性试验。保乳手术或乳房切除术后年龄至少 18 岁患有浸润性乳腺癌(pT1-3、pN0-1、M0)的患者符合资格。我们将患者随机分配至整个乳房或胸壁,分 15 次(超过 3 周)40 Gy、分 5 次 27 Gy(超过 1 周)或 26 Gy 分 5 次(超过 1 周)。由于干预的性质,分配并未被掩盖。主要终点是同侧乳腺肿瘤复发;假设 40 Gy 的 5 年发病率为 2%,非劣效性被预先定义为五次方案的 ≤1·6% 过量(临界风险比 [HR] 为 1·81)。由临床医生、患者和照片评估正常组织的影响。该试验已在 isrctn.com 注册,ISRCTN19906132。

 发现


2011年11月24日至2014年6月19日期间,我们招募了来自97个英国中心的4096名患者并获得了他们的同意,其中1361名患者被分配到40Gy计划,1367名被分配到27Gy计划,1368名被分配到26Gy计划。中位随访时间为 71·5 个月(IQR 71·3 至 71·7),主要终点事件发生在 79 名患者中(40 Gy 组 31 名,27 Gy 组 27 名,26 Gy 组 21 名)。 Gy组); 15 次照射中 27 Gy 的 HR 与 40 Gy 相比,5 次照射的 HR 为 0·86(95% CI 0·51 至 1·44),5 次照射 26 Gy 的 HR 为 0·67(0·38 至 1·16)。 40 Gy 后同侧乳腺肿瘤复发的 5 年发生率为 2·1%(1·4 至 3·1);与 15 次分割中的 40 Gy 相比,5 次分割中的 27 Gy 的估计绝对差异为 −0·3%(−1·0 至 0·9)(错误接受较差的五次分割方案的概率:p=0·002240 15 个分数中的 Gy)和 -0·7%(-1·3 至 0·3),5 个分数中为 26 Gy(p=0·00019对比15 个分数中的 40 Gy)。 5 年时,986 名 40 Gy 患者中的 98 名 (9·9%)、1005 名 27 Gy 患者中的 155 名 (15·4%) 报告了任何中度或显着的临床医生评估的乳房或胸壁正常组织影响,以及1020 名患者中的 121 名 (11·9%) 26 Gy 患者。在 1-5 年的所有临床医生评估中,15 次分次 40 Gy 的优势比为 1·55(95% CI 1·32 至 1·83,p<0·0001),5 次分次 27 Gy 的比值比为 1·55,5 次分次 27 Gy 的优势比为 1·12 (0·94 至 1·34,p=0·20),26 Gy,分 5 次。患者和照片评估显示,27 Gy 与 40 Gy 相比,正常组织影响风险较高,但 26 Gy 与 40 Gy 相比则不然。

 解释


1 周内分 5 次照射 26 Gy 不低于 3 周内分 15 次照射 40 Gy 的局部肿瘤控制标准,并且对于在术后接受辅助局部放疗的患者,在长达 5 年内对正常组织的影响方面是安全的。早期乳腺癌的初次手术。

 资金


国家卫生研究院卫生技术评估计划。

更新日期:2020-04-28
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