One versus three weeks hypofractionated whole breast radiotherapy for early breast cancer treatment: the FAST-Forward phase III RCT.

Autor:	Brunt AM; School of Medicine, University of Keele and University Hospitals of North Midlands, Staffordshire, UK.; Clinical Trials and Statistics Unit (ICR-CTSU), The Institute of Cancer Research, London, UK., Haviland JS; Clinical Trials and Statistics Unit (ICR-CTSU), The Institute of Cancer Research, London, UK., Wheatley DA; Department of Oncology, Royal Cornwall Hospital NHS Trust, Truro, UK., Sydenham MA; Clinical Trials and Statistics Unit (ICR-CTSU), The Institute of Cancer Research, London, UK., Bloomfield DJ; Sussex Cancer Centre, Brighton and Sussex University Hospitals, Brighton, UK., Chan C; Women's Health Clinic, Nuffield Health Cheltenham Hospital, Cheltenham, UK., Cleator S; Department of Oncology, Imperial Healthcare NHS Trust, London, UK., Coles CE; Department of Oncology, University of Cambridge, Cambridge, UK., Donovan E; Centre for Vision, Speech and Signal Processing, University of Surrey, Guildford, UK., Fleming H; Clinical and Translational Radiotherapy Research Group, National Cancer Research Institute, London, UK., Glynn D; Centre for Health Economics, University of York, York, UK., Goodman A; Oncology Unit, Torbay Hospital, Devon, UK., Griffin S; Centre for Health Economics, University of York, York, UK., Hopwood P; Clinical Trials and Statistics Unit (ICR-CTSU), The Institute of Cancer Research, London, UK., Kirby AM; Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, Sutton, UK and Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK., Kirwan CC; Division of Cancer Sciences, University of Manchester, Manchester, UK., Nabi Z; RTQQA, Mount Vernon Cancer Centre, Middlesex, UK., Patel J; Clinical Trials and Statistics Unit (ICR-CTSU), The Institute of Cancer Research, London, UK., Sawyer E; Comprehensive Cancer Centre, King's College London, London, UK., Somaiah N; Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, Sutton, UK and Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK., Syndikus I; Clatterbridge Cancer Centre, Clatterbridge Hospital NHS Trust, Cheshire, UK., Venables K; RTQQA, Mount Vernon Cancer Centre, Middlesex, UK., Yarnold JR; Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, Sutton, UK and Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK., Bliss JM; Clinical Trials and Statistics Unit (ICR-CTSU), The Institute of Cancer Research, London, UK.
Jazyk:	angličtina
Zdroj:	Health technology assessment (Winchester, England) [Health Technol Assess] 2023 Nov; Vol. 27 (25), pp. 1-176.
DOI:	10.3310/WWBF1044
Abstrakt:	Background: FAST-Forward aimed to identify a 5-fraction schedule of adjuvant radiotherapy delivered in 1 week that was non-inferior in terms of local cancer control and as safe as the standard 15-fraction regimen after primary surgery for early breast cancer. Published acute toxicity and 5-year results are presented here with other aspects of the trial. Design: Multicentre phase III non-inferiority trial. Patients with invasive carcinoma of the breast (pT1-3pN0-1M0) after breast conservation surgery or mastectomy randomised (1 : 1 : 1) to 40 Gy in 15 fractions (3 weeks), 27 Gy or 26 Gy in 5 fractions (1 week) whole breast/chest wall (Main Trial). Primary endpoint was ipsilateral breast tumour relapse; assuming 2% 5-year incidence for 40 Gy, non-inferiority pre-defined as < 1.6% excess for 5-fraction schedules (critical hazard ratio = 1.81). Normal tissue effects were assessed independently by clinicians, patients and photographs. Sub-Studies: Two acute skin toxicity sub-studies were undertaken to confirm safety of the test schedules. Primary endpoint was proportion of patients with grade ≥ 3 acute breast skin toxicity at any time from the start of radiotherapy to 4 weeks after completion. Nodal Sub-Study patients had breast/chest wall plus axillary radiotherapy testing the same three schedules, reduced to the 40 and 26 Gy groups on amendment, with the primary endpoint of 5-year patient-reported arm/hand swelling. Limitations: A sequential hypofractionated or simultaneous integrated boost has not been studied. Participants: Ninety-seven UK centres recruited 4096 patients (1361:40 Gy, 1367:27 Gy, 1368:26 Gy) into the Main Trial from November 2011 to June 2014. The Nodal Sub-Study recruited an additional 469 patients from 50 UK centres. One hundred and ninety and 162 Main Trial patients were included in the acute toxicity sub-studies. Results: Acute toxicity sub-studies evaluable patients: (1) acute grade 3 Radiation Therapy Oncology Group toxicity reported in 40 Gy/15 fractions 6/44 (13.6%); 27 Gy/5 fractions 5/51 (9.8%); 26 Gy/5 fractions 3/52 (5.8%). (2) Grade 3 common toxicity criteria for adverse effects toxicity reported for one patient. At 71-month median follow-up in the Main Trial, 79 ipsilateral breast tumour relapse events (40 Gy: 31, 27 Gy: 27, 26 Gy: 21); hazard ratios (95% confidence interval) versus 40 Gy were 27 Gy: 0.86 (0.51 to 1.44), 26 Gy: 0.67 (0.38 to 1.16). With 2.1% (1.4 to 3.1) 5-year incidence ipsilateral breast tumour relapse after 40 Gy, estimated absolute differences versus 40 Gy (non-inferiority test) were -0.3% (-1.0-0.9) for 27 Gy ( p = 0.0022) and -0.7% (-1.3-0.3) for 26 Gy ( p = 0.00019). Five-year prevalence of any clinician-assessed moderate/marked breast normal tissue effects was 40 Gy: 98/986 (9.9%), 27 Gy: 155/1005 (15.4%), 26 Gy: 121/1020 (11.9%). Across all clinician assessments from 1 to 5 years, odds ratios versus 40 Gy were 1.55 (1.32 to 1.83; p < 0.0001) for 27 Gy and 1.12 (0.94-1.34; p = 0.20) for 26 Gy. Patient and photographic assessments showed higher normal tissue effects risk for 27 Gy versus 40 Gy but not for 26 Gy. Nodal Sub-Study reported no arm/hand swelling in 80% and 77% in 40 Gy and 26 Gy at baseline, and 73% and 76% at 24 months. The prevalence of moderate/marked arm/hand swelling at 24 months was 10% versus 7% for 40 Gy compared with 26 Gy. Interpretation: Five-year local tumour incidence and normal tissue effects prevalence show 26 Gy in 5 fractions in 1 week is a safe and effective alternative to 40 Gy in 15 fractions for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer. Future Work: Ten-year Main Trial follow-up is essential. Inclusion in hypofractionation meta-analysis ongoing. A future hypofractionated boost trial is strongly supported. Trial Registration: FAST-Forward was sponsored by The Institute of Cancer Research and was registered as ISRCTN19906132. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 09/01/47) and is published in full in Health Technology Assessment ; Vol. 27, No. 25. See the NIHR Funding and Awards website for further award information.
Databáze:	MEDLINE
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