| Contributors: |
Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, UK; Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK. Electronic address: a.gilbert@leeds.ac.uk. Centre for Trials Research, Cardiff University Heath Park, Cardiff, UK. Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK. Sussex Cancer Centre, University Hospitals Sussex NHS Foundation Trust, Royal Sussex County Hospital, Brighton, UK. National Radiotherapy Trials QA (RTTQA) Group, Cardiff, UK; St. Bartholomew's Hospital, West Smithfield, London, UK. Patient representative, London, UK. Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, UK; National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre (BRC), Leeds, UK. Leeds Cancer Centre, St James's University Hospital, Leeds, UK. Bristol Haematology and Oncology Centre, Bristol, UK. Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, UK. Cancer Imaging, School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK. Department of Medical Physics & Biomedical Engineering, University College London, London, UK. Department of Pathology, University Hospitals Sussex NHS Foundation Trust, Royal Sussex County Hospital, Brighton, UK. Oxford University Hospitals NHS Foundation Trust, Department of Oncology, Churchill Hospital, Oxford, UK. The Royal Marsden Hospital, Institute of Cancer Research, Sutton, UK. Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Cancer Research Centre, NIHR Manchester Biomedical Research Centre, Manchester, UK; Christie NHS Foundation Trust, Manchester, UK. Royal Surrey Hospital, Guildford, UK; School of Biosciences, University of Surrey, Guildford, UK. Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, UK; Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK. |
| Description: |
BACKGROUND: Localised squamous cell carcinoma of the anus is treated with radical chemoradiotherapy. Cure rates are high, but treatment can result in substantial acute and long-term morbidity. We aimed to assess whether lower dose chemoradiotherapy maintains high local control rates in patients with early-stage disease, with the secondary aim of reducing toxicity. METHODS: ACT4 is a phase 2, prospective, multicentre, open-label, two-arm non-comparative, randomised, controlled trial, investigating reduced-dose intensity-modulated radiotherapy (rd-IMRT: 41·4 Gy in 23 fractions) in patients with early-stage anal cancer; T1-2 (≤4 cm) N0-NxM0. Eligible patients were at least 16 years of age, with an Eastern Cooperative Oncology Group performance status of 0-1. The primary outcome is 3-year loco-regional failure rates. Patients were randomly assigned 1:2 (with stratification by T stage, N stage, gender, HIV status, and randomising site) to standard-dose IMRT (sd-IMRT: 50·4 Gy in 28 fractions) or rd-IMRT with concurrent mitomycin and capecitabine chemotherapy. Here, we report the pre-planned, modified intention-to-treat analysis of secondary endpoints 6 months after treatment end-complete clinical response, compliance, patient-reported outcomes (EORTC QLQ-C30 and ANL27), and safety data. The trial is registered at the ISRCTN registry (ISRCTN88455282) and is ongoing but no longer recruiting. FINDINGS: 163 patients were recruited from 28 UK tertiary centres between April 24, 2017, and Dec 1, 2020. 160 patients were included in the primary analysis (sd-IMRT n=55; dr-IMRT n=105). Data on ethnicity were not collected. The median patient age was 66 years (IQR 58-72 years); 117 (73%) were female and 43 (27%) male; and 129 (94%) of 138 evaluable samples were p16 positive. Complete clinical responses at 6 months were 87% (46 of 53) for sd-IMRT and 92% (89 of 97) for rd-IMRT. Radiotherapy interruptions of 3 days or more occurred in 14 (26%) of 55 patients in sd-IMRT and 16 (15%) of 105 patients in rd-IMRT. Chemotherapy ... |