
==== Front
Int J Surg
Int J Surg
JS9
International Journal of Surgery (London, England)
1743-9191
1743-9159
Lippincott Williams & Wilkins Hagerstown, MD

38833345
IJS-D-24-01682
10.1097/JS9.0000000000001750
00141
3
Correspondence
Letter to the editor for the article ‘Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study’
Wang Lexin MD abc1418801292@qq.com

Wu Qibiao MD qbwu@must.edu.mo
a
Chi Hao MD adChihao7511@163.com

Yang Guanhu MD ae*guanhuyang@gmail.com

a Faculty of Chinese Medicine, and State Key Laboratory of Quality Research in Chinese Medicine, and University Hospital, Macau University of Science and Technology, Macau, Macao SAR
b General Hospital of Ningxia Medical University
c Ningxia Medical University, Yinchuan, Ningxia
d Clinical Medical College, Southwest Medical University, Luzhou, People’s Republic of China
e Department of Specialty Medicine, Ohio University, Athens, Ohio, USA
* Corresponding author. Address: Faculty of Chinese Medicine, and State Key Laboratory of Quality Research in Chinese Medicine, and University Hospital, Macau University of Science and Technology, Macau, Macao SAR, People’s Republic of China; Department of Specialty Medicine, Ohio University, Athens 45701, Ohio, USA. Tel.: +513 652 5688. E-mail: guanhuyang@gmail.com (G. Yang).
9 2024
4 6 2024
110 9 60266027
25 4 2024
20 5 2024
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/

OPEN-ACCESSTRUE
==== Body
pmc Dear Editor,

A fascinating study was conducted on the progression of gastric cancer (GC). The article entitled ‘Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study,’ authored by Li et al.1, published in the International Journal of Surgery. The author’s research found that a new treatment approach that received neoadjuvant sintilimab in combination with FLOT chemotherapy has the potential to enhance advanced cancer prognosis. However, the authors have made outstanding contributions to the GC prognosis. However, we believe that further discussion is necessary to reach some important conclusions. First, the author studies the report showing that 25 (86.2%) received adjuvant therapy, which implies that the insufficient neoadjuvant sintilimab combination with FLOT chemotherapy patients affects the accuracy and clinical significance of the experimental conclusions. Hence, the number of patients receiving adjuvant therapy should be increased in order to obtain a more accurate assessment of its effectiveness for GC.

Second, Li et al.’s research found that the patients who received neoadjuvant sintilimab combination with FLOT chemotherapy experienced adverse reactions, such as lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). Considering the limited number of patients involved in the trial and individual variations, it is not possible to accurately determine whether this unfavorable prognosis is common or coincidental. It is suggested that the author increase the number of GC patients who receive neoadjuvant sintilimab in combination with FLOT chemotherapy. This will allow for the observation of the relationship between the occurrence of adverse reactions and prognosis in adjuvant therapy.

Third, the IL6 and HRAS genes were found to be highly and minimally expressed in TRG0 [complete responders (CRs), n=5] compared to TRG3 [non-responders (NRs), n=3] through biological analysis. However, the author did not confirm the regulatory function of the expressed IL6 and HRAS genes in response to the neoadjuvant sintilimab combination with FLOT chemotherapy.

Fourth, the authors should thoroughly investigate the mechanism of the TRG0 group and the TRG3 group. It is recommended to utilize single-cell multi-omics analysis to verify the regulation mechanisms of the mTOR signaling pathway and T-cell receptor signaling pathway2. This analysis should include potential modifications such as methylation, acetylation, and ubiquitination, which offer new possibilities for treating GC. Additionally, we recommend that the author conduct in-vitro and in-vivo experiments to verify the molecular regulatory mechanism3.

Finally, I would like to express my gratitude to the author for the conclusion of the article and their contribution to clinical treatment.

Ethical approval

Not applicable.

Consent

All the authors consent for the publication of the article.

Source of funding

This work was supported by the Science and Technology Development Fund, Macau SAR (Nos: 0098/2021/A2 and 0048/2023/AFJ), the National Natural Science Foundation of China (No.: 82361168663), and Macau University of Science and Technology’s Faculty Research Grant (No: FRG-23-003-FC).

Author contribution

L.W., Q.W., H.C., and G.Y.: conceptualization, methodology, validation, formal analysis, investigation, resources, writing – original draft, writing – review and editing, supervision, and project administration; Y.H., W.S., M.H., and L.L.: data curation.

Conflicts of interest disclosure

The authors declare that they have no conflicts of interest.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Lexin Wang, Qibiao Wu, Hao Chi, and Guanhu Yang.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Provenance and peer review

Not applicable.

Assistance with the study

Not applicable.

Lexin Wang, Qibiao Wu, and Hao Chi contributed equally to this work.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Published online 4 June 2024
==== Refs
References

1 Li N Li Z Fu Q . Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study. Int J Surg 2024;110 :2071–2084.38320099
2 Tang F Li J Qi L . A pan-cancer single-cell panorama of human natural killer cells. Cell 2023;186 :4235–4251.e20.37607536
3 Martisova A Holcakova J Izadi N . DNA methylation in solid tumors: functions and methods of detection. Int J Mol Sci 2021;22 :4247.33921911
