Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Nov 24, 2021; 12(11): 1064-1071
Published online Nov 24, 2021. doi: 10.5306/wjco.v12.i11.1064
Modulated electro-hyperthermia in stage III and IV pancreatic cancer: Results of an observational study on 158 patients
Giammaria Fiorentini, Donatella Sarti, Girolamo Ranieri, Cosmo Damiano Gadaleta, Caterina Fiorentini, Carlo Milandri, Andrea Mambrini, Stefano Guadagni
Giammaria Fiorentini, Department of Onco-Hematology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro 61122, Italy
Donatella Sarti, Oncology Department, Ospedale S. Maria Della Misericordia, ASUR1, Urbino 61029, Italy
Girolamo Ranieri, Cosmo Damiano Gadaleta, Interventional and Integrated Medical Oncology, National Cancer Research Centre, IRCCS Istituto Tumori "Giovanni Paolo II", Bari 70124, Italy
Caterina Fiorentini, Department of Medical Biothecnologies, Division of Cardiology, University Hospital of Siena, Siena 53100, Italy
Carlo Milandri, Medical Oncology Unit, San Donato Hospital, Arezzo 52100, Italy
Andrea Mambrini, Department of Oncology - ASL Toscana Nord Ovest, Massa Carrara Hospital, Massa 54100, Italy
Stefano Guadagni, Applied Clinical Sciences and Biotechnology, Section of General Surgery, University of L’Aquila, L’Aquila 67100, Italy
Author contributions: Fiorentini G, Sarti D and Guadagni S wrote the paper; Ranieri G and Gadaleta CD performed the data collection; Fiorentini C collected and evaluated the interactions between hyperthermia and heart; Milandri C and Mambrini A reviewed the manuscript.
Institutional review board statement: The study was reviewed and approved by the Istituto Tumori Giovanni Paolo II, Bari, Italy Institutional Review Board (Approval No. 948/CE).
Informed consent statement: All study participants provided informed written consent prior to study enrolment.
Conflict-of-interest statement: No conflict of interest.
Data sharing statement: No further technical appendix, statistical code, and dataset are available.
STROBE statement: The authors have read and revised the manuscript based on the STROBE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Giammaria Fiorentini, MD, Adjunct Professor, Chief Doctor, Director, Department of Onco-Hematology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Via Lombroso, Pesaro 61122, Italy. g.fiorentini2020@gmail.com
Received: February 23, 2021
Peer-review started: February 23, 2021
First decision: May 7, 2021
Revised: May 18, 2021
Accepted: September 30, 2021
Article in press: September 30, 2021
Published online: November 24, 2021

An increasing number of studies report the beneficial effects of regional hyperthermia in association with chemotherapy (CHT) and radiotherapy for the treatment of pancreatic cancer; in particular, the use of modulated electro-hyperthermia (mEHT) results in increased survival and tumor response.


To compare outcomes of CHT alone or in association with mEHT for the treatment of stage III and IV pancreatic cancer.


This was an observational retrospective study; data were collected for patients with stage III-IV pancreatic cancer that were treated with CHT alone or in combination with mEHT from 2003 to 2019. A total of 158 patients were included in the study out 270 patients screened in four Italian hospitals; 58 (37%) of these received CHT + mEHT and 100 (63%) CHT. CHT was mainly gemcitabine-based regimens in both groups.


Overall (19.5 mo vs 11.02 mo, P < 0.001) and progression-free (12 mo vs 3 mo, P < 0.001) survival were better for the CHT + mEHT group compared to the CHT group. The association of mEHT resulted also in an improvement of tumor response with disease control rate 95% vs 58% (P < 0.001) at 3 mo. Toxicity was comparable in the two study groups, and mEHT related adverse events were limited in 8 patients presenting G1-2 skin burns.


The addition of mEHT to systemic CHT improved overall and progression-free survival and local tumor control with comparable toxicity.

Keywords: Modulated electro-hyperthermia, Locally advanced pancreatic cancer, Tumor response, Survival

Core Tip: Modulated electro-hyperthermia is a relatively new regional hyperthermia method. It targets tumor cell membranes and extracellular matrix to increase their temperature. New studies have appeared in tumor palliation reporting incremental benefits of chemotherapy and radiotherapy and few additional side effects. In patients with stage III and IV pancreatic cancer, modulated electro-hyperthermia in association with chemotherapy results in significant improvements of overall and progression-free survival and tumor response with comparable toxicity.