Minireviews
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2022; 14(1): 181-202
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.181
Trimodality treatment in gastric and gastroesophageal junction cancers: Current approach and future perspectives
Nikolaos Charalampakis, Sergios Tsakatikas, Dimitrios Schizas, Stylianos Kykalos, Maria Tolia, Rodanthi Fioretzaki, Georgios Papageorgiou, Ioannis Katsaros, Ahmed Adel Fouad Abdelhakeem, Matheus Sewastjanow-Silva, Jane E Rogers, Jaffer A Ajani
Nikolaos Charalampakis, Sergios Tsakatikas, Rodanthi Fioretzaki, Georgios Papageorgiou, Department of Medical Oncology, Metaxa Cancer Hospital of Piraeus, Piraeus 18537, Greece
Dimitrios Schizas, TheFirst Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens 11527, Greece
Stylianos Kykalos, TheSecond Propedeutic Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens 11527, Greece
Maria Tolia, Department of Radiation Oncology, University Hospital of Crete, Heraklion 71110, Greece
Ioannis Katsaros, Department of General Surgery, Metaxa Cancer Hospital of Piraeus, Piraeus 18537, Greece
Ahmed Adel Fouad Abdelhakeem, Matheus Sewastjanow-Silva, Jane E Rogers, Jaffer A Ajani, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
Author contributions: Charalampakis N, Tsakatikas S and Schizas D wrote the paper; Kykalos S, Tolia M, Fioretzaki R, Papageorgiou G and Katsaros I collected the data; Abdelhakeem Adel Fouad A, Sewastjanow-Silva M, Rogers EJ and Ajani AJ revised the manuscript.
Conflict-of-interest statement: The authors have no conflict of interest related to the manuscript.
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: Nikolaos Charalampakis, MD, PhD, Medical Oncologist, Department of Medical Oncology, Metaxa Cancer Hospital of Piraeus, Mpotasi 51, Piraeus 18537, Greece. nick301178@yahoo.com
Received: March 25, 2021
Peer-review started: March 25, 2021
First decision: June 16, 2021
Revised: June 28, 2021
Accepted: December 10, 2021
Article in press: December 10, 2021
Published online: January 15, 2022
Abstract

Gastric and gastroesophageal junction (GEJ) cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage, with an increasing incidence both in Asia and in Western countries. These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses. Accordingly, the understanding of phenotypic and genotypic correlations/classifications has been improved. Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone, with the incorporation of other treatment modalities, such as radiation and chemotherapy (including biologics). Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival. Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate, which is associated with improved long-term outcomes. Several studies have defined various chemotherapy regimens to accompany radiation (before and after surgery). Recently, addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval. Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results. The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers, highlight the remaining questions and present the current research effort addressing them.

Keywords: Gastric cancer, Gastroesophageal junction cancer, Trimodality treatment, Chemoradiotherapy, Surgery, Immunotherapy

Core Tip: Trimodality treatment combining chemotherapy, radiation and surgery is an effective management of locally advanced gastric and gastroesophageal cancers, although the extent of benefit remains to be answered in future clinical trials. Addition of newer therapeutic agents, such as immune checkpoint inhibitors may further enhance the curative potential of this approach.