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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

Brunt, Adrian Murray; Haviland, Joanne S; Wheatley, Duncan A; Sydenham, Mark A; Alhasso, Abdulla; Bloomfield, David J; Chan, Charlie; Churn, Mark; Cleator, Susan; Coles, Prof Charlotte E; Goodman, Andrew; Harnett, Adrian; Hopwood, Penelope; Kirby, Anna M; Kirwan, Cliona C; Morris, Carolyn; Nabi, Zohal; Sawyer, Elinor; Somaiah, Navita; Stones, Liba; Syndikus, Isabel; Bliss, Judith M; Yarnold, John R; Management Group, FAST-Forward Trial

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 Thumbnail


Authors

Joanne S Haviland

Duncan A Wheatley

Mark A Sydenham

Abdulla Alhasso

David J Bloomfield

Charlie Chan

Mark Churn

Susan Cleator

Prof 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

FAST-Forward Trial Management Group



Contributors

Abdulla Alhasso
Other

Anne Armstrong
Other

Judith Bliss
Other

David Bloomfield
Other

Jo Bowen
Other

Murray Brunt
Other

Charlie Chan
Other

Hannah Chantler
Other

Mark Churn
Other

Susan Cleator
Other

Charlotte Coles
Other

Ellen Donovan
Other

Andy Goodman
Other

Susan Griffin
Other

Jo Haviland
Other

Penny Hopwood
Other

Anna Kirby
Other

Julie Kirk
Other

Cliona Kirwan
Other

Marjory MacLennan
Other

Carolyn Morris
Other

Zohal Nabi
Other

Elinor Sawyer
Other

Mark Sculphur
Other

Judith Sinclair
Other

Navita Somaiah
Other

Liba Stones
Other

Mark Sydenham
Other

Isabel Syndikus
Other

Jean Tremlett
Other

Karen Venables
Other

Duncan Wheatley
Other

John Yarnold
Other

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. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Journal Article Type Article
Acceptance Date Apr 9, 2020
Online Publication Date Apr 28, 2020
Publication Date 2020-05
Publicly Available Date May 26, 2023
Journal The Lancet
Print ISSN 0140-6736
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 395
Issue 10237
Pages 1613 - 1626
DOI https://doi.org/10.1016/S0140-6736%2820%2930932-6
Publisher URL https://www.sciencedirect.com/science/article/pii/S0140673620309326
Related Public URLs https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30932-6/fulltext

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