{
  "abstract": "Introduction The incidence of anal carcinoma is increasing, with the current gold standard treatment being chemoradiotherapy. There is currently a wide range in the radiotherapy dose used internationally which may lead to overtreatment of early-stage disease and potential undertreatment of locally advanced disease.PLATO is an integrated umbrella trial protocol which consists of three trials focused on assessing risk-adapted use of adjuvant low-dose chemoradiotherapy in anal margin tumours (ACT3), reduced-dose chemoradiotherapy in early anal carcinoma (ACT4) and dose-escalated chemoradiotherapy in locally advanced anal carcinoma (ACT5), given with standard concurrent chemotherapy.Methods and analysis The primary endpoints of PLATO are locoregional failure (LRF)-free rate for ACT3 and ACT4 and LRF-free survival for ACT5. Secondary objectives include acute and late toxicities, colostomy-free survival and patient-reported outcome measures. ACT3 will recruit 90 participants: participants with removed anal tumours with margins ≤1 mm will receive lower dose chemoradiotherapy, while participants with anal tumours with margins >1 mm will be observed. ACT4 will recruit 162 participants, randomised on a 1:2 basis to receive either standard-dose intensity modulated radiotherapy (IMRT) in combination with chemotherapy or reduced-dose IMRT in combination with chemotherapy. ACT5 will recruit 459 participants, randomised on a 1:1:1 basis to receive either standard-dose IMRT in combination with chemotherapy, or one of two increased-dose experimental arms of IMRT with synchronous integrated boost in combination with chemotherapy.Ethics and dissemination This study has been approved by Yorkshire & The Humber – Bradford Leeds Research Ethics Committee (ref: 16/YH/0157, IRAS: 204585), July 2016. Results will be disseminated via national and international conferences, peer-reviewed journal articles and social media. A plain English report will be shared with the study participants, patients’ organisations and media.Trial registration number ISRCTN88455282.",
  "authors": [
    {
      "affiliations": [
        "Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"
      ],
      "name": "Russell Frood"
    },
    {
      "affiliations": [
        "Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"
      ],
      "name": "Alexandra Gilbert"
    },
    {
      "affiliations": [
        "MRC Clinical Trials Unit, University College London, London, UK"
      ],
      "name": "Duncan Gilbert"
    },
    {
      "affiliations": [
        "National Radiotherapy Trials QA, Velindre Cancer Centre, Cardiff, UK"
      ],
      "name": "Natalie L Abbott"
    },
    {
      "affiliations": [
        "Leeds Institute of Medical Research, University of Leeds, Leeds, UK",
        "NIHR Leeds Biomedical Research Centre, Leeds NHS Teaching Hospitals, Leeds, UK"
      ],
      "name": "Susan D Richman"
    },
    {
      "affiliations": [
        "Cancer Imaging, King’s College London School of Biomedical Engineering & Imaging Sciences, London, UK"
      ],
      "name": "Vicky Goh"
    },
    {
      "affiliations": [
        "Gastrointestinal Unit, Royal Marsden NHS Foundation Trust, London, UK"
      ],
      "name": "Sheela Rao"
    },
    {
      "affiliations": [
        "Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"
      ],
      "name": "Joanne Webster"
    },
    {
      "affiliations": [
        "Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"
      ],
      "name": "Alexandra Smith"
    },
    {
      "affiliations": [
        "Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"
      ],
      "name": "Joanne Copeland"
    },
    {
      "affiliations": [
        "Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"
      ],
      "name": "Sharon P Ruddock"
    },
    {
      "affiliations": [
        "Patient Representative, London, UK"
      ],
      "name": "Lindy Berkman"
    },
    {
      "affiliations": [
        "Oxford University Hospitals NHS Foundation Trust, Oxford, UK"
      ],
      "name": "Rebecca Muirhead"
    },
    {
      "affiliations": [
        "Division of Cancer Sciences, University of Manchester, Manchester, UK"
      ],
      "name": "Andrew G Renehan"
    },
    {
      "affiliations": [
        "Hillingdon Hospitals NHS Foundation Trust, Uxbridge, UK"
      ],
      "name": "Mark Harrison"
    },
    {
      "affiliations": [
        "Velindre Cancer Centre, Cardiff, Wales, UK"
      ],
      "name": "Richard Adams"
    },
    {
      "affiliations": [
        "Medical Physics and Biomedical Engineering, University College London, London, UK"
      ],
      "name": "Maria Hawkins"
    },
    {
      "affiliations": [
        "Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"
      ],
      "name": "Sarah Brown"
    },
    {
      "affiliations": [
        "Leeds Institute of Medical Research, University of Leeds, Leeds, UK"
      ],
      "name": "David Sebag-Montefiore"
    }
  ],
  "title": "Personalising anal cancer radiotherapy dose (PLATO): protocol for a multicentre integrated platform trial",
  "uid": "9769e231-69b8-5e45-b2f2-b7ad8384fc61"
}