S708
Clinical – Lower GI
ESTRO 2026
14 Department of Radiology, The Christie NHS Foundation Trust, Manchester, United Kingdom. 15 Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. 16 Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, United Kingdom. 17 Department of Oncology, Rigshospitalet, Technical University Hospital of Greater Copenhagen, Copenhagen, Denmark Purpose/Objective: To assess whether mesorectal-only escalated-dose radiotherapy (EDRT) increases 6-month clinical complete response (cCR) rate compared to standard- dose radiotherapy (SDRT) in early rectal cancer patients. Material/Methods: APHRODITE is a phase II multi-centre open-label 2-arm randomised controlled trial (ISRCTN:16158514). Patients had MRI-defined early rectal adenocarcinoma (T1-3bN0-1bM0, non-threatened resection margin) unsuitable for radical total mesorectal excision (TME) or suitable for TME but strongly preferring organ preservation. They were randomised (1:2) to SDRT (50.4Gy/28 daily fractions) to primary tumour plus a novel mesorectum-only volume, or EDRT as above including a primary tumour 62Gy synchronous integrated boost. IMRT and daily CBCT were mandated. Use of concurrent capecitabine was chosen per-patient pre-randomisation. The primary outcome was cCR rate at 6 months post RT start, assessed with combined MRI/sigmoidoscopy/digital examination. With 80% power and 1-sided type 1 error rate of 20%, 104 patients were required to detect an increase from 35% to 55% in cCR (incorporating 5% loss). Secondary endpoints included treatment compliance, acute side effects (CTCAEv5) and patient-reported outcomes (PROs:QLQ-C30/QLQ-CR29/LARS). For patients with cCR, active surveillance was encouraged. Patients will be followed to 24 months for clinical outcomes, late side effects, and PROs. APHRODITE was funded by Yorkshire Cancer Research (RA/2017/R1/001). Results: Eleven UK sites randomised 119 participants (24/2/2020-11/11/2024); 39 to SDRT and 80 to EDRT. Six randomised participants (3 each arm) did not start trial treatment and were excluded from the modified intention to treat (mITT) population (Table 1).Radiotherapy and chemotherapy treatment compliance were similar across arms (Table 1). Clinician-reported acute side effects to 6 months (Table 2) were generally low (overall 12% grade ≥ 3 events), but with slightly higher rates of bowel and anorectal side effects with EDRT. PROs to 6 months will be presented at ESTRO.Six-month cCR rates for SDRT and EDRT were 12 (33.3%) and 38 (49.4%) respectively; absolute difference 16.0%, 80% one-sided
whereas worsening of cognitive functioning, diarrhoea, financial difficulties, body image, abdominal and buttock pain showed an inverse correlation with age. Conclusion: Despite often being classified as ECOG 1, older patients in our study demonstrated comparable survival rates and less deterioration in QoL than their younger peers. However, the higher incidence of local recurrence in early-onset and older patients requires further investigation. Female patients experienced greater deterioration in QoL during TNT, as well as a lower cCR/pCR ratio, but no meaningful difference in long-term QoL or survival compared to male patients. Supportive and restaging strategies for female patients should be critically reassessed. Keywords: rectal cancer; clinical trial, Quality of life APHRODITE: A prospective phase II randomised controlled trial of dose-escalated vs standard dose (chemo)radiotherapy in early rectal cancer Simon Gollins 1 , Eleanor M Hudson 2 , Matthew Norris 2 , Monica Jefford 3 , Alwyn Burrage 4 , Claire Arthur 5 , Rebecca Muirhead 6,7 , Ravi Adapala 8 , Simon P Bach 9 , Alexandra Gilbert 10 , Maria Hawkins 11 , Debra Howard 12 , James Iddenden 13 , Rohit Kochhar 14 , Mark Saunders 5 , Mark Teo 15 , Edward JD Webb 16 , Nicholas West 10 , Alexandra Smith 2 , Samantha Noutch 2 , Rebecca Day 2 , Sarah R Brown 2 , David Sebag-Montefiore 10 , Ane L Appelt 10,17 1 Department of Oncology, Shrewsbury and Telford NHS Trust, Shrewsbury, United Kingdom. 2 Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom. 3 Patient Advocate, NA, London, United Kingdom. 4 Patient Advocate, NA, Conwy North Wales, United Kingdom. 5 Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom. 6 Department of Oncology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. 7 Department of Oncology, University of Oxford, Oxford, United Kingdom. 8 Department of Radiology, Wrexham Maelor Hospital, Wrexham, United Kingdom. 9 School of Medical Sciences, University of Birmingham, Birmingham, United Kingdom. 10 Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom. 11 Medical Physics and Biomedical Engineering, University College London, London, United Kingdom. 12 National Radiotherapy Trials QA (RTTQA) Group, Mount Vernon Cancer Centre, Middlesex, United Kingdom. 13 National Radiotherapy Trials QA (RTTQA) Group, Clatterbridge Cancer Center, Liverpool, United Kingdom. Proffered Paper 2319
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