ESTRO 2025 - Abstract Book

S447

Clinical - Breast

ESTRO 2025

1 School of Medicine, University of Keele, Keele, United Kingdom. 2 Oncology, University Hospital of North Midlands, Stoke-on-Trent, United Kingdom. 3 Sunrise Cancer Centre, Royal Cornwall Hospitals NHS Trust, Truro, United Kingdom. 4 Clinical Trials and Statistics Unit (ICR-CTSU), Institute of Cancer Research, Sutton, United Kingdom. 5 Radiotherapy department, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. 6 Breast surgery, Nuffield Hospital, Cheltenham, United Kingdom. 7 Oncology, Imperial College Healthcare NHS Trust, London, United Kingdom. 8 Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. 9 Patient advocate, Former NCRI CTRad, London, United Kingdom. 10 Oncology, Torbay District General Hospital, Torquay, United Kingdom. 11 Academic Radiotherapy, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom. 12 Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. 13 Radiotherapy Trials Quality Assurance (RTTQA), The Hillingdon Hospitals NHS Foundation Trust, Uxbridge, United Kingdom. 14 Breast cancer radiotherapy, Guy’s and St Thomas’ Hospital, London, United Kingdom. 15 Radiotherapy, Charing Cross Hospital, London, United Kingdom. 16 Oncology, The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, United Kingdom. 17 Radiotherapy Quality Assurance, Mount Vernon Hospital, London, United Kingdom Purpose/Objective: The FAST-Forward trial showed that a radiotherapy schedule of 26Gy in 5 fractions (Fr) delivered over 1 week to the breast or chest wall was as safe and effective as the standard 3-week schedule (40Gy in 15 fractions) for patients with early breast cancer. The FAST-Forward prospective randomised nodal sub-study (ISRCTN19906132) investigates whether a 5-fraction (1-week) schedule is also as safe for adjuvant radiotherapy to level I-IV axilla. The 5-year primary analysis of sub-study normal tissue effects (NTEs) is presented. Material/Methods: Patients with invasive breast cancer (pT1-3 pN1-3a M0) who had undergone breast surgery with axillary staging +/- dissection and required radiotherapy to the axilla (any or all levels I-IV) in addition to the breast/chest wall were randomised (1:1:1) to 40Gy/15Fr over 3 weeks (control), 26Gy/5Fr over 1 week or 27Gy/5Fr over 1 week. Whilst sub study recruitment was ongoing, the 27Gy arm was closed based on 3-year NTEs in the main trial suggesting 26Gy/5Fr was likely to be optimal. Hence, this analysis focusses on 40Gy/15Fr vs 26Gy/5Fr. The primary endpoint was 5-year patient-reported arm/hand swelling (from EORTC QLQ-BR23). 10% were expected to report moderate/marked swelling with 40Gy/15Fr and we aimed to exclude a 10% increase with 26Gy/5Fr (non-inferiority, 90% power, one-sided α=0.05). Secondary endpoints were patient- and clinician-reported late NTEs focussing on arm/shoulder symptoms. Efficacy is not expected to differ in nodal and breast tissue; sub-study data will contribute to a future meta-analysis with the main trial. Results: 467 patients were randomised between 04/2016-10/2018 from 50 UK centres (181 40Gy/15Fr, 182 26Gy/5Fr, 104 27Gy/5Fr). Median age was 61 years; 250 (54%) and 182 (39%) had grade 2 and 3 tumours respectively; 261 (56%) had an axillary level II/III dissection. 83% (307/369) of expected 5-year questionnaires were returned. Moderate/marked arm/hand swelling was reported by 11/107 (10%) with 40Gy/15Fr and 13/116 (11%) for 26Gy/5Fr, a difference of 0.93% (90% CI -5.9, 7.7), p=0.49, within the non-inferiority margin. Other arm/shoulder symptoms at 5 years were similar in the two groups (table 1). Arm lymphoedema was reported by clinicians for 13/131 (10%) with 40Gy/15Fr and 20/139 (14%) for 26Gy/5Fr, p=0.27. There were no confirmed cases of brachial plexopathy. The 27Gy/5Fr comparison was under-powered and non-inferiority cannot be confirmed (table 1).