英国伦敦癌症研究所Adrian Murray Brunt团队近日取得一项新成果。他们比较了低分割乳腺放疗1周与3周的5年疗效和安全性。2020年4月28日该研究发表在《柳叶刀》杂志上。

研究组的目标是确定对于早期乳腺癌初次手术后的患者，1周内实施5分割辅助放疗方案在局部癌症控制方面不逊于国际标准的15分割常规治疗方案，且同样安全。

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、临床3期、随机、非劣效性试验。2011年11月24日至2014年6月19日，研究组招募了4096位浸润性乳腺癌（pT1-3、pN0-1、M0）患者，年龄均大于18岁，均接受了保乳手术或乳房切除术。在获得患者的同意后，将其随机分组，其中1361位接受全乳或胸壁40 Gy/15f放疗3周，1367位接受27 Gy/5f放疗1周，1368位接受26 Gy/5f放疗1周。

中位随访71.5个月后，共有79例患者发生同侧乳腺肿瘤复发，其中40 Gy组31例，27 Gy组27例，26 Gy组21例；与40 Gy/15f相比，27 Gy/5f的风险比为0.86，26 Gy/5f的风险比为0.67。

40 Gy组同侧乳腺肿瘤5年内复发率为2.1%；与40 Gy/15f相比，27 Gy/5f的复发率绝对值降低0.3%，26 Gy/5f降低0.7%。5年内，40 Gy组中有9.9%的患者发生乳腺或胸壁中等或临床评估的正常组织效应，27 Gy组中有15.4%，26 Gy组中有11.9%。

在1-5年的所有临床评估中，与40 Gy/15f相比，27 Gy/5f的比值比为1.55，26 Gy/5f为1.12。患者和影像评估显示，与40 Gy相比，27 Gy的正常组织效应风险较高，但26 Gy风险未增加。

总之，对于早期乳腺癌初次手术后进行局部辅助放疗的患者，26 Gy/5f放疗1周以控制局部肿瘤的疗效，不劣于标准的40 Gy/15f放疗3周，且5年正常组织效应风险未增加。

附：英文原文

Title: 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

Author: Adrian Murray Brunt, Joanne S Haviland, Duncan A Wheatley, Mark A Sydenham, Abdulla Alhasso, David J Bloomfield, Charlie Chan, Mark Churn, Susan Cleator, Charlotte E Coles, Andrew Goodman, Adrian Harnett, Penelope Hopwood, Anna M Kirby, Cliona C Kirwan, Carolyn Morris, Zohal Nabi, Elinor Sawyer, Navita Somaiah, Liba Stones, Isabel Syndikus, Judith M Bliss, John R Yarnold, Abdulla Alhasso, Anne Armstrong, Judith Bliss, David Bloomfield, Jo Bowen, Murray Brunt, Charlie Chan, Hannah Chantler, Mark Churn, Susan Cleator, Charlotte Coles, Ellen Donovan, Andy Goodman, Susan Griffin, Jo Haviland, Penny Hopwood, Anna Kirby, Julie Kirk, Cliona Kirwan, Marjory MacLennan, Carolyn Morris, Zohal Nabi, Elinor Sawyer, Mark Sculphur, Judith Sinclair, Navita Somaiah, Liba Stones, Mark Sydenham, Isabel Syndikus, Jean Tremlett, Karen Venables, Duncan Wheatley, John Yarnold

Issue&Volume: 2020-04-28

Abstract: 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.

DOI: 10.1016/S0140-6736(20)30932-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30932-6/fulltext