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Personalising anal cancer radiotherapy dose (PLATO): protocol for a multicentre integrated platform trial

Title: Personalising anal cancer radiotherapy dose (PLATO): protocol for a multicentre integrated platform trial
Authors: Frood, R; Gilbert, A; Gilbert, D; Abbott, NL; Richman, SD; Goh, V; Rao, S; Webster, J; Smith, A; Copeland, J; Ruddock, SP; Berkman, L; Muirhead, R; Renehan, AG; Harrison, M; Adams, R; Hawkins, M; Brown, S; Sebag-Montefiore, D
Publisher Information: BMJ Publishing Group
Publication Year: 2025
Collection: Oxford University Research Archive (ORA)
Description: 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. ...
Document Type: article in journal/newspaper
Language: English
DOI: 10.1136/bmjopen-2025-109655
Availability: https://doi.org/10.1136/bmjopen-2025-109655; https://ora.ox.ac.uk/objects/uuid:a93b6d74-0a1c-4074-a5c5-d70de2172d2d
Rights: info:eu-repo/semantics/openAccess ; CC Attribution (CC BY)
Accession Number: edsbas.BB5D403C
Database: BASE