CC BY-NC-ND 4.0 · Endosc Int Open 2023; 11(05): E451-E459
DOI: 10.1055/a-2033-9831
Original article

Endoscopic calcium electroporation for colorectal cancer: a phase I study

Malene Broholm
1   Center for Surgical Science, Department of Surgery, Zealand University Hospital, Denmark
,
Rasmus Vogelsang
1   Center for Surgical Science, Department of Surgery, Zealand University Hospital, Denmark
,
Mustafa Bulut
1   Center for Surgical Science, Department of Surgery, Zealand University Hospital, Denmark
2   Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
,
Trine Stigaard
1   Center for Surgical Science, Department of Surgery, Zealand University Hospital, Denmark
,
Hanne Falk
3   Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
Stine Frandsen
4   Center for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde, Denmark
,
Dorte Levin Pedersen
5   Department of Radiology, Zealand University Hospital, Denmark
,
Trine Perner
5   Department of Radiology, Zealand University Hospital, Denmark
,
Anne-Marie Kanstrup Fiehn
1   Center for Surgical Science, Department of Surgery, Zealand University Hospital, Denmark
2   Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
6   Department of Pathology, Zealand University Hospital, Denmark
,
Ida Mølholm
7   Visiopharm, Hoersholm, Denmark
,
Michael Bzorek
6   Department of Pathology, Zealand University Hospital, Denmark
,
Andreas Weinberger Rosen
1   Center for Surgical Science, Department of Surgery, Zealand University Hospital, Denmark
,
Christina Søs Auður Andersen
6   Department of Pathology, Zealand University Hospital, Denmark
,
Niels Pallisgaard
6   Department of Pathology, Zealand University Hospital, Denmark
,
Ismail Gögenur
1   Center for Surgical Science, Department of Surgery, Zealand University Hospital, Denmark
2   Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
,
Julie Gehl
2   Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
3   Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
4   Center for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde, Denmark
› Author Affiliations
Supported by: Enhanced perioperative oncology (EPEONC) consortium
Supported by: Kræftens Bekæmpelse http://dx.doi.org/10.13039/100008363 R110-A6996

TRIAL REGISTRATION: Prospective trial NCT03542214 at ClinicalTrials.gov (http://www.clinicaltrials.gov/)

Abstract

Background and study aims Colorectal cancer is one of the most common malignancies, with approximately 20 % of patients having metastatic disease. Local symptoms from the tumor remain a common issue and affect quality of life. Electroporation is a method to permeabilize cell membranes with high-voltage pulses, allowing increased passage of otherwise poorly permeating substances such as calcium. The aim of this study was to determine the safety of calcium electroporation for advanced colorectal cancer.

Patients and methods Six patients with inoperable rectal and sigmoid colon cancer were included, all presenting with local symptoms. Patients were offered endoscopic calcium electroporation and were followed up with endoscopy and computed tomography/magnetic resonance scans. Biopsies and blood samples were collected at baseline and at follow-up, 4, 8, and 12 weeks after treatment. Biopsies were examined for histological changes and immunohistochemically with CD3/CD8 and PD-L1. In addition, blood samples were examined for circulating cell-free DNA (cfDNA).

Results A total of 10 procedures were performed and no serious adverse events occurred. Prior to inclusion, patients reported local symptoms, such as bleeding (N = 3), pain (N = 2), and stenosis (N = 5). Five of six patients reported symptom relief. In one patient, also receiving systemic chemotherapy, clinical complete response of primary tumor was seen. Immunohistochemistry found no significant changes in CD3 /CD8 levels or cfDNA levels after treatment.

Conclusions This first study of calcium electroporation for colorectal tumors shows that calcium electroporation is a safe and feasible treatment modality for colorectal cancer. It can be performed as an outpatient treatment and may potentially be of great value for fragile patients with limited treatment options.

Supplementary material



Publication History

Received: 23 September 2022

Accepted after revision: 09 February 2023

Accepted Manuscript online:
13 February 2023

Article published online:
09 May 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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