ESTRO 2025 - Abstract Book

S1268

Clinical – Lower GI

ESTRO 2025

4065

Poster Discussion THUNDER 2 - Theragnostic utilities for neoplastic diseases of the rectum by MRI-guided radiotherapy - Phase II study: definitive results Giuditta Chiloiro 1 , Luca Boldrini 1 , Angela Romano 1 , Flavia De Giacomo 1 , Huong Elena Tran 1 , Francesco Bono 1 , Lana Smiljanic 2 , Elisa Meldolesi 1 , Giulia Panza 1 , Silvia Di Franco 1 , Marco Valerio Antonelli 1 , Claudio Votta 1 , Matteo Nardini 1 , Lorenzo Placidi 1 , Maria Antonietta Gambacorta 1,2 1 Radiation Oncology Department, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy. 2 Radiation Oncology Department, Catholic University of the Sacred Heart, Rome, Italy Purpose/Objective: The primary aim of the THUNDER 2 study is to increase the complete response (CR) rate by 10% in patients with locally advanced rectal cancer (LARC) identified as non-responders based on the Early Tumour Regression Index (ERI) treated by Magnetic Resonance guided Radiation Therapy (MRIgRT). We present the definitive results, focusing on CR rates. Material/Methods: The trial enrolled LARC patients with stage cT2-3 or cT4 with anal sphincter involvement, N0-2, without high-risk features. The number of cases to be enrolled is 63 to improve pCR from 3% to 13% in non-responders. All patients underwent MRIgRT treatment with a simultaneous integrated boost (SIB)2 approach at 55 Gray (Gy) to the rectal tumor and the corresponding mesorectum, and 45 Gy to the elective nodes. At the 10th fraction, the ERI was calculated. If the ERI value was ≥13.1, the patient was considered “non-responder” and a new SIB3 treatment was scheduled by intensifying the RT dose to the residual rectal tumor + 3 mm margin from the 11th fraction onwards up to a total dose of 60.1 Gy. Otherwise, if the ERI was <13.1, the patient was considered "responder" and the original plan was maintained. Continuous administration of fluoropyrimidine-based chemotherapy was combined. Differences in patient characteristics between responders and non-responders were assessed using the chi-squared or Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables. The CR was assessed in terms of pathological CR (pCR) or persistent clinical CR (cCR) at 2 years. Results: A total of 62/63 patients (death from non-oncological causes before restaging) enrolled between March 2021 and May 2024 were included in the analysis. Patient characteristics are reported in Table 1. Thirty two (50.8%) were classified as responders and 31 (49.2%) as non-responders. Overall, 37.1% achieved CR, 51.6% in responders and 22.6% in non-responders. When looking at major response in terms of Tumour Regression Grade by Mandard (TRG) 1-2, the percentage reached 59.7% in the overall population and 71.0% in responders, while it was 48.4% in non-responders. CR was 100%, 36.2% and 0% with ERI< 5, ERI between 5 and 36 and ERI≥36, respectively. Overall, 18 (29%) patients were candidates for conservative approach, 15 in responder and 3 in non-responder group (Figure 1).