ESTRO 2025 - Abstract Book

S1193

Clinical – Lower GI

ESTRO 2025

Kingdom. 11 Department of Radiology, Royal Marsden Hospital NHS Trst, London, United Kingdom. 12 CRUK and University College London Cancer Trials Centre, University College London, London, United Kingdom. 13 Clinical Oncology, Velindre NHS Trust, Cardiff, United Kingdom Purpose/Objective: To determine if the addition of irinotecan to capecitabine chemoradiation (CRT) improves disease-free survival in MRI-defined locally advanced rectal cancer (LARC). Material/Methods: ARISTOTLE (ISRCTN:09351447) is a phase III, multi-centre, open-label trial that randomly assigned (1:1) patients with MRI-defined LARC threatening or involving resection margins without metastases to pre-operative radiotherapy:45Gy/25 fractions combined with either capecitabine 900mg/m 2 (CRT) or 650 mg/m 2 bd weekdays with Irinotecan iv once-weekly 60mg/m 2 (IrCRT) weeks 1-4. The primary endpoint is disease-free survival (DFS). Results: 75 UK sites randomised 564 eligible patients from 10/2011 to 07/2018; 284 to CRT and 280 to IrCRT. 66% male; median age 61 years (range:24-83). Radiological staging in both arms was similar:mrT3(77%), mrT4(16%); mrCRM involved(49%);resection margin threatened ≤1mm(38%). Median follow-up is 62.1 months.Compared with CRT, IrCRT patients were less likely to receive 45Gy RT: 208(75%) vs 251(89%), p < 0.001; or receive ≥90% capecitabine dose:187(68%) in IrCRT vs 253(89%) CRT, p < 0.001. 205(74%) IrCRT patients received ≥90% irinotecan dose. ≥Gd 3 non-haematological adverse events included fatigue 17(6%) vs 8(3%) p=0.06; diarrhoea:14% vs 4% p<0.001; abdominal pain 5% vs <1% p=0.001 for IrCRT and CRT respectively. ≥Gd 3 haematological adverse events included leucopaenia: 9% vs 2%, p<0.001; neutropaenia: 10% vs 1%,p<0.001; and febrile neutropaenia: 1% vs <1% for IrCRT and CRT respectively. 5 patients had a grade 5 adverse event (3 lrCRT,2 CRT). The median time from the end of RT to surgery was 10.6 weeks. 238(85%) and 243(86%) patients underwent surgery in the IrCRT and CRT arms. The R0 resection rate was 90% vs 89% p=0.75 for IrCRT and CRT respectively. The pCR rate was 20% for IrCRT vs 18% for CRT p = 0.52. The rate of any post-surgical complications was similar in both arms:94(39%) for IrCRT and 91(37%) for CRT p=0.65). There is no evidence of a difference in loco-regional failure free (HR 0.94 [0.46-1.90]p=0.86, distant metastasis free (HR 0.89 [0.63-1.25] p=0.51), disease free HR 0.87 [0.64-1.18] p=0.37) or overall survival (HR 0.91[0.63-1.30],p=0.59) when IrCRT is compared with CRT.