ESTRO 2025 - Abstract Book

S1246

Clinical – Lower GI

ESTRO 2025

3665

Proffered Paper PLATO ACT 4: Long term results of an RCT evaluating reduced dose and standard dose chemoradiotherapy in early-stage anal cancer (ISRCTN:88455282) David Sebag-Montefiore 1 , Mark Harrison 2 , Alexandra Gilbert 1 , Natalie Abbott 3,4 , Lindy Berkman 5 , Joanne Copeland 6 , Duncan Gilbert 7 , Chloe Gaul 6 , Rob Glynne-Jones 2 , Vicky Goh 8 , Maria Hawkins 9 , Rebecca Muirhead 10 , Sheela Rao 11 , Andrew Renehan 12 , Susan Richman 1 , Sharon Ruddock 6 , Alexandra Smith 6 , Joanne Webster 6 , Sarah Brown 6 , Richard Adams 13 1 Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, United Kingdom. 2 Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, United Kingdom. 3 National Radiotherapy Trials QA (RTTQA) Group, National Radiotherapy Trials QA (RTTQA) Group, Cardiff, United Kingdom. 4 St. Bartholomew’s Hospital, St. Bartholomew’s Hospital, London, United Kingdom. 5 Patient Advocate, N/A, London, United Kingdom. 6 Clinical Trials Research Unit, University of Leeds, Leeds, United Kingdom. 7 Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, United Kingdom. 8 School of Biomedical Engineering & Imaging Sciences, King's College London, London, United Kingdom. 9 Dept of Medical Physics & Biomedical Engineering, University College London, London, United Kingdom. 10 Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, United Kingdom. 11 Institute of Cancer Research, Royal Marsden, London, United Kingdom. 12 Division of Cancer Sciences, School of Medical Sciences, University of Manchester, Manchester, United Kingdom. 13 Centre for Trials Research, Cardiff University, Cardiff, United Kingdom Purpose/Objective: To determine if reduced dose (rd) intensity modulated radiotherapy (IMRT) results in an acceptably high 3-year locoregional failure (LRF) free rate and reduced toxicity in early-stage anal cancer. Material/Methods: ACT4 is a phase II prospective, multi-centre, two-arm non-comparative randomised trial, embedded within the PLATO platform. Patients with T1-2(≤4cm) N0/xM0 anal cancer were randomised 1:2 to standard dose (sd) IMRT: 50.4Gy in 28 fractions (F) or rd-IMRT: 41.4Gy in 23F with concurrent mitomycin 12mg/m2 D1 and capecitabine 825mg/m2 twice daily on RT days. A single-stage design was used to determine if rd-IMRT results in an acceptably low rate of LRF and reduced toxicity. 123 patients were required to demonstrate rd-IMRT does not produce efficacy rates <80% (LRF≥20%) assuming efficacy rates of ≥90% (LRF<10%) with 5% alpha. The sample size was inflated to 162 for analysis of p16+ genotype outcomes. The primary end point is 3-year LRF-free rate. Results: 163 patients were randomised from 28 UK sites (sd-IMRT n=55; rd-IMRT n=108) between April 2017 and November 2020, with 3 rd-IMRT patients excluded for the modified intention to treat analysis (Table 1). 45 (90.0%) and 84 (95.5%) of patients were p16+ve in the sd-IMRT and rd-IMRT arms respectively. Median follow-up is 50.4months (9.0 73.6months). Chemotherapy and radiotherapy compliance and acute toxicity have been reported 1 . The 3-year LRF rate was 16.4% for sd-IMRT and 12.4% rd-IMRT (LRF-free rate 87.6%, 90% confidence interval (CI) 81.0-92.5). The 3-year LRF rate was 13.1% (11/84) for p16+ve patients in the rd-IMRT arm. Pelvic failure was reported at the primary site in 4 sd-IMRT (7.3%) and 8 rd-IMRT (7.6%) patients; 1 sd-IMRT (1.8%) and 2 rd-IMRT (1.9%) patients at the primary site and a node (2 inguinal; 1 other). There were no isolated nodal failures. 12 patients (7.5%) underwent salvage surgery. High rates of progression-free, disease free, colostomy free and overall survival were observed for rd-IMRT (Table 2). Patient reported outcomes (EORTC QLQ-C30 and ANL27) measuring late toxicity were similar in both arms up to 3-years (reported in detail in companion abstract).