Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Feb 27, 2023; 15(2): 222-233
Published online Feb 27, 2023. doi: 10.4240/wjgs.v15.i2.222
Efficacy and safety of preoperative immunotherapy in patients with mismatch repair-deficient or microsatellite instability-high gastrointestinal malignancies
Ying-Jie Li, Xin-Zhi Liu, Yun-Feng Yao, Nan Chen, Zhong-Wu Li, Xiao-Yan Zhang, Xin-Feng Lin, Ai-Wen Wu
Ying-Jie Li, Xin-Zhi Liu, Nan Chen, Ai-Wen Wu, Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
Yun-Feng Yao, Gastro-intestinal Ward III, Beijing Cancer Hospital, Beijing 100142, China
Zhong-Wu Li, Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
Xiao-Yan Zhang, Department of Radiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
Xin-Feng Lin, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China
Author contributions: Wu AW contributed to conception and design of the study, draft and final approval of the manuscript; Li YJ contributed to collection of the data, draft the manuscript, study design and statistical analysis; Wu AW, Li YJ, Liu XZ and Yao YF, Li ZW, Zhang XY, Lin XF contributed to quality control of the study especially the surgery part, acquisition of data; All authors approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82173156; Beijing Hospitals Authority Clinical Medicine Development of Special Funding, No. ZYLX202116.
Institutional review board statement: This study was approved by the ethics committee of Peking University cancer hospital (approval no. 2022YJZ39).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at drwuaw@sina.com.
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: Ai-Wen Wu, MD, PhD, Academic Editor, Director, Doctor, Professor, Surgeon, Teacher, Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing 100142, China. drwuaw@sina.com
Received: November 29, 2022
Peer-review started: November 29, 2022
First decision: December 27, 2022
Revised: January 8, 2023
Accepted: February 1, 2023
Article in press: February 1, 2023
Published online: February 27, 2023
Processing time: 90 Days and 3.1 Hours
ARTICLE HIGHLIGHTS
Research background

Neoadjuvant programmed death protein (PD)-1 blockade immunotheapy has been sufficiently applied in a variety of cancers, but was rare in metastatic mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal malignancies. Since the NICHE Study have showed their inspiring results that neoadjuvant immunotherapy was an efficient and safe method to improve colon cancer patients’ outcome, NCCN guideline then recommend immune checkpoint inhibitors to cT4b gastric or colorectal cancer. However, whether preoperative immunotherapy can expand to other stage gastrointestinal malignancies is still unknown.

Research motivation

We performed this study among 36 initially surgical resected difficult dMMR/MSI-H gastrointestinal malignancies such gastric cancer, duodenal cancer and colorectal cancer patients who received preoperative PD-1 blockade immunotherapy followed by surgery in order to investigate if the indication of preoperative immunotherapy can expand to initially surgical resected difficult dMMR/MSI-H gastrointestinal malignancies and evaluate the safety and efficacy.

Research objectives

To the best of our knowledge, this retrospective study is one of the few to summarize dMMR/MSI-H gastric, duodenal, and colorectal cancers for preoperative immunotherapy. The cohort was a sequential case analysis that only one patient was excluded from the cohort because symptoms disappeared after PD1 therapy and she refused to examination and further treatment.

Research methods

The limitations of this study included its small sample size, retrospective design, short follow-up time, and different neoadjuvant regimens and cycles. However, our study was a real-world clinical study in patients who required preoperative immunotherapy, and the group was a continuous case cohort, with the exception of one patient who declined to be enrolled because of resolution of symptoms.

Research results

Our study demonstrated that preoperative PD-1 blockade immunotherapy with or without chemotherapy could achieve significant effect and acceptable adverse events in dMMR/MSI-H gastrointestinal malignancies.

Research conclusions

Our study demonstrated that preoperative PD-1 blockade immunotherapy with or without chemotherapy could achieve significant effect and acceptable adverse events in dMMR/MSI-H gastrointestinal malignancies. Some low rectal cancer or duodenal cancer can achieve clinical complete response and avoid surgery to achieve organ preservation. Large sample clinical trials are needed.

Research perspectives

This study compared preoperative immunotherapy for dMMR/MSI-H in different gastrointestinal tumors, and showed that specific treatment strategies could be used for different tumor sites. It was encouraging to find that a high proportion of dMMR/MSI-H duodenal and low rectal cancers did not require surgery after preoperative immunotherapy, and this treatment strategy deserves further investigation.