1. 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
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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, Anne Armstrong, Judith Bliss, David Bloomfield, Jo Bowen, Murray Brunt, Hannah Chantler, Charlotte Coles, Ellen Donovan, Andy Goodman, Susan Griffin, Jo Haviland, Penny Hopwood, Anna Kirby, Julie Kirk, Cliona Kirwan, Marjory MacLennan, Mark Sculphur, Judith Sinclair, Mark Sydenham, Jean Tremlett, Karen Venables, Duncan Wheatley, John Yarnold, and Apollo - University of Cambridge Repository
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medicine.medical_treatment ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Radiotherapy, Adjuvant/adverse effects ,Clinical endpoint ,030212 general & internal medicine ,Neoplasm Metastasis ,Mastectomy ,Neoplasm Recurrence, Local/epidemiology ,Aged, 80 and over ,Manchester Cancer Research Centre ,United Kingdom/epidemiology ,Hazard ratio ,General Medicine ,Middle Aged ,Treatment Outcome ,Female ,Radiation Dose Hypofractionation ,Adult ,Breast Neoplasms/mortality ,Breast Neoplasms ,Risk Assessment ,Article ,03 medical and health sciences ,Breast cancer ,medicine ,Humans ,Risk Assessment/methods ,Radiation Injuries ,Aged ,Neoplasm Staging ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,medicine.disease ,R1 ,United Kingdom ,Mastectomy/methods ,Radiation therapy ,Clinical trial ,Regimen ,Radiation Injuries/epidemiology ,Radiotherapy, Adjuvant ,Neoplasm Grading ,Neoplasm Recurrence, Local ,business ,Nuclear medicine ,RA ,Follow-Up Studies - 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, pINTERPRETATION: 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.
- Published
- 2020
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