Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 21, 2022; 10(3): 899-918
Published online Jan 21, 2022. doi: 10.12998/wjcc.v10.i3.899
Dynamic monitoring of carcinoembryonic antigen, CA19-9 and inflammation-based indices in patients with advanced colorectal cancer undergoing chemotherapy
Nebojsa Manojlovic, Goran Savic, Bojan Nikolic, Nemanja Rancic
Nebojsa Manojlovic, Clinic for Gastroenterology and Hepatology, Military Medical Academy, Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade 11000, Serbia
Goran Savic, Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia, Military Medical Academy, Belgrade 11000, Serbia
Bojan Nikolic, Institute for Radiology, Military Medical Academy, Belgrade 11000, Serbia
Nemanja Rancic, Center for Clinical Pharmacology, Institute for Radiology, Military Medical Academy, Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade 11000, Serbia
Author contributions: Manojlovic N was the guarantor and designed the study, participated in the acquisition, analysis and interpretation of the data, and drafted the initial manuscript; Savic G and Rancic N participated in the analysis, acquisition, interpretation of the data, and drafted the initial manuscript; Nikolic B participated in the acquisition, analysis, and interpretation of the data.
Institutional review board statement: The study protocol was reviewed and approved by the Ethics Committee of Military Medical Academy (approval number: No 8/2021), and the study was conducted in accordance with the Helsinki Declaration as revised in 2013.
Informed consent statement: All study participants, or their legal guardian, provided written consent prior to study enrollment.
Conflict-of-interest statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at [nebojsa.manojlovic1@gmail.com]. Participants gave informed consent for data sharing.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: Nebojsa Manojlovic, PhD, Associate Professor, Clinic for Gastroenterology and Hepatology, Military Medical Academy, Faculty of Medicine of the Military Medical Academy, University of Defence, Crnotravska 17, Belgrade 11000, Serbia. nebojsa.manojlovic1@gmail.com
Received: July 19, 2021
Peer-review started: July 19, 2021
First decision: October 3, 2021
Revised: October 21, 2021
Accepted: December 25, 2021
Article in press: December 25, 2021
Published online: January 21, 2022
ARTICLE HIGHLIGHTS
Research background

The roles of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) in monitoring the patient response to chemotherapy for metastatic colorectal cancer (mCRC) are not well defined and accepted as standard practice. Inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) are important predictors for disease course and outcome, but have not widely investigated in the monitoring of mCRC. There is unmet need for simple, safe, cheap and accurate method in monitoring of the patients response to chemotherapy for mCRC.

Research motivation

The main topic of the study was to evaluate the significance and usefulness of dynamic change of tumor markers CEA and CA19-9 in comparison with standard method for monitoring the chemotherapy response for mCRC. The key problem was to find representative cut-off values for PD and DC. The another topic was to evaluate correlation and concordance of the dynamic changes in the inflammatory indices with standard method for monitoring the chemotherapy response for MCRC and with the tumour markers. The significance of this study is to help to define role of CEA and CA19-9 in monitoring the chemotherapy response for mCRC, and to evaluate the potential role of the inflammatory indices in the same purpose.

Research objectives

The main objectives was to find correlation and concordance od the dynamic change of the tumor markers CEA and CA19-9 and the inflammatory indices with the standard method for monitoring the chemotherapy response, to find representative cut-off values for PD. The another main objective was to evaluate clinical significance of the tumor markers and the inflammatory indices using CUI. All main objectives were realized. Realization of our main objectives better defined the role of CEA, pointed out the role of CA19-9 and the potential role of inflammatory indices in the monitoring chemotherapy response in mCRC which should be further investigated.

Research methods

We performed baseline CT before beginning of the chemotherapy along with the tumour markers CEA and CA19-9 and CBC with the inflammatory indices NLR, PLR, LMR and SII. During monitoring of chemotherapy response we repeated all baseline values after 3 of 4 cycles of chemotherapy in the period of 10-12 wk, and after following 3 or 4 cycles of chemotherapy in the following 10-12 wk. CT- based evaluation of response was performed according to RECIST 1.1 criteria, and the tumors markers and inflammatory indices according to the according to the change in the percent from the baseline value or at nadir calculated as ∆CEA1 = [(CEA2-CEA1)/CEA 1] × 100, ∆CEA2 = [(CEA 3- CEA nadir or 2)/CEA nadir or 2] × 100. The same formula was used for the CA19-9 and inflammatory indices. Statistical analyses were conducted using IBM SPSS Statistics, version 26.0.

Research results

A total of 102 mCRC patients participated in this study. The tumour markers CEA and CA19-9 and all inflammatory indices except LMR significantly correlated with the CT-based response to chemotherapy in patients with mCRC. The best PD cut-off value for CEA was 24.52%, for CA19-9 21.49%, for inflammatory indices NLR 11.05%, PLR 5.9%, SII -6.04%. The cut- off with maximal Se for excluding PD was -60.85% for CEA and -55.38% for CA19-9, allowing for the safe avoidance of 25.49% and 16.92% of CT control examinations. In the multivariate analysis, only CEA was a significant predictor of outcome. CEA had good overall utility FC, CA19-9 had a satisfactory overall utility FC, and the inflammatory indices poor overall utility.

Research conclusions

CEA is useful in monitoring of the chemotherapy response in patients with mCRC and can substitute a quarter of CT control examinations. CA19-9 could be useful in certain circumstances. The inflammatory indices NLR, PLR and SII should be further investigated into their use in chemotherapy monitoring for patients with mCRC.

Research perspectives

Future research should investigate potential of the combinations of the tumor markers and the inflammatory indices in monitoring chemotherapy response in mCRC.