Abstract
SummaryBackgroundWe 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.MethodsFAST-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.FindingsBetween 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.Interpretation26 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.FundingNational Institute for Health Research Health Technology Assessment Programme.
Highlights
The Early Breast Cancer Trialists’ Collaborative Group systematic overview confirms that radiotherapy after primary surgery in women with early-stage cancers reduces locoregional cancer recurrence and breast cancer deaths, including patients with positive lymph nodes treated by mastectomy and axillary clearance.[1,2] For many decades, schedules of adjuvant radiotherapy for these patients delivered 25 fractions of 2 Gy over 5 weeks
Between Nov 24, 2011, and June 19, 2014, 4110 patients were enrolled in the FAST-Forward trial
After a median follow-up of 71·5 months (IQR 71·3 to 71·7), ipsilateral breast tumour relapse was recorded in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); hazard ratios (HRs) versus 40 Gy in 15 fractions were 0·86 for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions
Summary
The Early Breast Cancer Trialists’ Collaborative Group systematic overview confirms that radiotherapy after primary surgery in women with early-stage cancers reduces locoregional cancer recurrence and breast cancer deaths, including patients with positive lymph nodes treated by mastectomy and axillary clearance.[1,2] For many decades, schedules of adjuvant radiotherapy for these patients delivered 25 fractions of 2 Gy over 5 weeks. University Hospitals of North Midlands and University of Keele, Stoke on Trent, UK (Prof A Murray Brunt FRCR); Clinical Trials and Statistics Unit, The Institute of Cancer Research, Sutton, London, UK (Prof A Murray Brunt, J S Haviland MSc, M A Sydenham BSc, Prof P Hopwood MD, L Stones BA, Prof J M Bliss MSc); Royal Cornwall Hospital, Treliske, Truro, UK (D A Wheatley FRCR); Beatson West of Scotland Cancer Centre, Glasgow, UK (A Alhasso FRCR); Brighton and Sussex University Hospitals, Brighton, UK (D J Bloomfield FRCR); Nuffield Health Cheltenham Hospital, Cheltenham, UK (C Chan FRCS); Worcestershire Acute Hospitals NHS Trust, Worcester, UK (M Churn FRCR); Imperial Healthcare NHS Trust, London, UK (S Cleator FRCR); University of Cambridge, Cambridge, UK (Prof C E Coles FRCR); Royal Devon and Exeter NHS Foundation Trust, Exeter, UK (A Goodman FRCR); Torbay Hospital NHS Foundation Trust, Torquay, UK (A Goodman); Norfolk and Norwich University Hospital, Norwich, UK (A Harnett FRCR); The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, UK
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