Personalising radiotherapy dose in anal cancer (PLATO) Platform: 6-month patient reported outcomes across ACT3, ACT4 and ACT5 trials

Gilbert, Alexandra, Gaul, Chloe, Webster, Joanne, Brown, Sarah R., Copeland, Joanne and Adams, Richard ORCID: https://orcid.org/0000-0003-3915-7243 2026. Personalising radiotherapy dose in anal cancer (PLATO) Platform: 6-month patient reported outcomes across ACT3, ACT4 and ACT5 trials. Radiotherapy and Oncology 223 , 111706. 10.1016/j.radonc.2026.111706

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Abstract

Purpose The Personalising Radiotherapy Dose in Anal Cancer (PLATO) platform was designed to evaluate risk‑adapted dose optimisation for anal squamous cell carcinoma (ASCC). A key secondary objective was to assess the impact of tailored treatment on patient‑reported outcomes (PROs), using the EORTC QLQ‑ANL27, the first anal cancer–specific validated PRO. Methods PLATO comprises three integrated trials: ACT3 (adjuvant chemoradiotherapy vs observation following local excision of T1N0/x anal margin tumours), ACT4 (reduced‑ vs standard‑dose chemoradiotherapy for T1/2 ≤ 4 cmN0/x ASCC), and ACT5 (three dose‑escalated chemoradiotherapy regimens for T3/4 or TanyN + disease). PROs (EORTC QLQ‑C30, QLQ-ANL27) were collected at baseline, end of treatment, 6-weeks, 6, 12, 24 and 36-months. Descriptive analyses to 6-months defined clinically relevant change as > 10‑point differences in mean scores. Results Between 1/2/2017–31/8/2023, 709 patients were recruited across 36 UK sites; 706 formed the mITT population (PRO consent 98.9 %; 86.0 % completion at 6-months). ACT5 patients reported markedly worse function and symptom scores at baseline than ACT3 and ACT4. All treated groups showed large declines at end of treatment, with improvement to baseline by 6-months for most issues; however, ACT5 participants continued to report residual deficits for bowel function compared with ACT3/4 cohorts. Poorer sexual function was reported in the ACT4 standard‑dose and ACT5 arms at 6-months, with interpretation of ACT3 sexual function limited by small numbers. Conclusion PLATO demonstrates the feasibility of risk‑adapted radiotherapy dosing, with excellent PRO compliance. Most quality-of-life deficits improved by 6-months, although persistent impairments remained in ACT5 patients. Follow‑up to 36-months will further define late effects.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine Research Institutes & Centres > Centre for Trials Research (CNTRR)
Additional Information:	For full list of authors see article webpage https://doi.org/10.1016/j.radonc.2026.111706
Publisher:	Elsevier
ISSN:	0167-8140
Date of First Compliant Deposit:	30 July 2026
Date of Acceptance:	13 July 2026
Last Modified:	30 Jul 2026 08:53
URI:	https://orca.cardiff.ac.uk/id/eprint/188621

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