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World J Gastroenterol. Apr 7, 2022; 28(13): 1288-1303
Published online Apr 7, 2022. doi: 10.3748/wjg.v28.i13.1288
Locoregional therapies and their effects on the tumoral microenvironment of pancreatic ductal adenocarcinoma
Thomas Lambin, Cyril Lafon, Robert Andrew Drainville, Mathieu Pioche, Frédéric Prat
Thomas Lambin, Cyril Lafon, Robert Andrew Drainville, LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Univ Lyon, Lyon 69003, France
Thomas Lambin, Mathieu Pioche, Department of Gastroenterology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon 69008, France
Frédéric Prat, Service d’Endoscopie Digestive, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy 92110, France
Frédéric Prat, INSERM U1016, Institut Cochin, Université de Paris, Paris 75014, France
Author contributions: Lambin T and Prat F reviewed the literature and prepared the manuscript; Lafon C, Drainville RA, and Pioche M contributed to and revised the manuscript; all authors approved the final manuscript.
Supported by the Labex DEVweCan (Université de Lyon) and PCSI ITMO Cancer INSERM.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Frédéric Prat, MD, Doctor, Service d’Endoscopie Digestive, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, 100 Bd du Général Leclerc, Clichy 92110, France. Frederic.prat@aphp.fr
Received: December 7, 2021
Peer-review started: December 7, 2021
First decision: January 27, 2022
Revised: February 10, 2022
Accepted: February 27, 2022
Article in press: February 27, 2022
Published online: April 7, 2022
Processing time: 112 Days and 18.3 Hours
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately 8%, with only 20% of patients eligible for surgery at the time of diagnosis. The tumoral microenvironment (TME) of the PDAC is one of the main causes for resistance to antitumoral treatments due to the presence of tumor vasculature, stroma, and a modified immune response. The TME of PDAC is characterized by high stiffness due to fibrosis, with hypo microvascular perfusion, along with an immunosuppressive environment that constitutes a barrier to effective antitumoral treatment. While systemic therapies often produce severe side effects that can alter patients’ quality of life, locoregional therapies have gained attention since their action is localized to the pancreas and can thus alleviate some of the barriers to effective antitumoral treatment due to their physical effects. Local hyperthermia using radiofrequency ablation and radiation therapy - most commonly using a local high single dose - are the two main modalities holding promise for clinical efficacy. Recently, irreversible electroporation and focused ultrasound-derived cavitation have gained increasing attention. To date, most of the data are limited to preclinical studies, but ongoing clinical trials may help better define the role of these locoregional therapies in the management of PDAC patients.

Keywords: Pancreatic ductal adenocarcinoma; Tumoral microenvironment; Stroma; Hyperthermia; Radiation therapy; High-intensity focused ultrasound

Core Tip: The prognosis of pancreatic ductal adenocarcinoma is poor, with a 5-year survival rate of approximately 8%. This is mainly due to an unfavorable tumoral microenvironment (tumor vasculature, stroma, and immune response). Locoregional therapies can alleviate some barriers to effective antitumoral treatment. This review explores the action of locoregional treatments on pancreatic cancer, with a specific focus on hyperthermia, radiation therapy, high-intensity focused ultrasound, and irreversible electroporation. After a description of the particularities of the tumoral microenvironment of pancreatic cancer, the effects of these treatments on the tumoral microenvironment and implications for future management of patients are discussed.