Organ Sparing for Locally Advanced Rectal Cancer after Neoadjuvant Treatment Followed by Electrochemotherapy.

Daniela Rega,Guglielmo Nasti,Cinzia Sassaroli,Fabiana Tatangelo,Gerardo Botti,Antonio Avallone,Roberta Fusco,Biagio Pecori,Carmela Romano,Ugo Pace,Valeria D’Alessio,Piera Maiolino,Massimiliano Di Marzo,Paolo Delrio,Vincenza Granata,Antonella Petrillo,Carmela Cervone

doi:10.3390/cancers13133199

Abstract

Simple SummaryThis is a Phase II randomized controlled trial conducted with the aim of investigating whether the use of Electrochemotherapy after neoadjuvant therapy (ECT) and before surgery in patients with major clinical response allows for a more conservative surgical approach in patients with Locally Advanced Rectal Cancer (LARC) in comparison with the control group that will not receive ECT. The treatment response, in both the control arm and in the treatment arm, will be assessed using the histopathological tumor regression grade on tissue specimens after local excision.Background: Currently, 45–55% of rectal cancer patients receive preoperative chemo- radio-therapy for Locally Advanced Rectal Cancer (LARC). The idea of our study is to use Electrochemotherapy (ECT) before surgery, in patients with major clinical response after neoadjuvant therapy, to allow for a more conservative surgical approach. Objective: To evaluate the increase of the complete response rate after neoadjuvant treatment in LARC and to spare organ function due to total mesorectal excision (TME). Patients and Methods: This is a Phase II randomized controlled trial enrolling 70 patients that will be developed in two stages. In the first step, 28 patients will be enrolled: 14 of these will receive ECT for four weeks after neo-adjuvant treatment and then local excision (treatment group) and 14 patients will receive neo-adjuvant treatment and then local excision (control group). If an increase of response rate is observed in the first stage, and/or feasibility/safety is demonstrated, the second stage of the trial will be performed, enrolling an additional 42 patients. The treatment response. in both the control arm and the treatment arm, will be assessed using the histopathological tumor regression grade on tissue specimens after local excision.

Highlights

Electroporation (EP) is a technique that is able to increase the permeability of the cell membrane by applying a short and intense electrical field that allows molecules that are not, or barely, permeable, to enter into the cell
If a complete response rate to the tumor regression grade (TRG) after local excision is noted in less than 25% of patients in the treatment group and/or feasibility/safety was not demonstrated, the study will be discontinued, otherwise a further 42 patients will be enrolled in the study
If a complete response rate to the TRG after local excision is noted in less than 25% of patients in the treatment group, and/or feasibility/safety was not demonstrated, the study will be discontinued

Summary

Introduction

Electroporation (EP) is a technique that is able to increase the permeability of the cell membrane by applying a short and intense electrical field that allows molecules that are not, or barely, permeable, to enter into the cell. The feasibility and benefits of ECT have been observed and documented in deep solid tumors, such as liver metastasis, primitive liver tumors (cholangiocarcinoma and hepatocellular carcinoma) and pancreatic tumors, both in preclinical and clinical studies [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26], overcoming the difficulty of obtaining the complete electroporation of target lesions. The idea of our study is to use Electrochemotherapy (ECT) before surgery, in patients with major clinical response after neoadjuvant therapy, to allow for a more conservative surgical approach. If an increase of response rate is observed in the first stage, and/or feasibility/safety is demonstrated, the second stage of the trial will be performed, enrolling an additional 42 patients

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