IMRT-VMAT in Locally Advanced Rectal Adenocarcinoma: An Observational Multicenter Prospectic Study on Total Neoadiuvant Radiotherapy According Rapido Trial

Background: The phase III multicenter randomized RAPIDO trial (Rectal Cancer And Preoperative Induction therapy followed by Dedicated Operation) has shown the advantege of Total Neoadjuvant treatment (TNT) with short course radiotherapy (RT). However, data on local control have not been confirmed at 5.6 years median follow-up in favor of the TNT arm because patients from the experimental (EXP) group received more often 3D-CRT (p=0.029). The primary end-point of this multicentric observational prospectic study is to assess the real life safety and efficacy of RAPIDO trial protocol using VMAT and IMRT treatment in all enrolled patients. Moreover FDG-PET and MRI images for predictive features compared with cancer phenotype (status of K-ras and EGFR) and study on tumor microenviroment response to short course RT will be also provided. Methods: Locally advanced rectal cancer patients undergoing TNT as defined in RAPIDO trial will be enrolled and prospectively included in this study. MRI and FDG-PET will be performed to staging and restaging the disease. The tumor microenviroment changes assessment with immunophenotype and soluble PDL1 and on EVCs will be done. For sample size calculation, using OR 0.5, 100 patients will be enrolled into two years. Kaplan -model and proportional Cox method will be adopoted for OS, DFS and predictive factors for local control. Conclusions: The results of this study will be useful to assess prospectively the safety and effectiveness of VMAT and IMRT in short course TNT assuming predictive factors for response through radiomics, metabolomics and immunological features. Trial Registration: COMITATO ETICO UNICO REGIONALE (CEUR) N.50/2022; San Carlo Hospital, Potenza, Italy.