Shin K, Jung EK, Park SJ, Jeong S, Kim IH, Lee MA. Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy. World J Gastrointest Oncol 2021; 13(8): 915-928 [PMID: 34457195 DOI: 10.4251/wjgo.v13.i8.915]
Corresponding Author of This Article
Myung-ah Lee, MD, PhD, Professor, Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul 06591, South Korea. angelamd@catholic.ac.kr
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Gastrointest Oncol. Aug 15, 2021; 13(8): 915-928 Published online Aug 15, 2021. doi: 10.4251/wjgo.v13.i8.915
Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy
Kabsoo Shin, Eun-Kyo Jung, Se Jun Park, Sangwoon Jeong, In-Ho Kim, Myung-ah Lee
Kabsoo Shin, Eun-Kyo Jung, Se Jun Park, Sangwoon Jeong, In-Ho Kim, Myung-ah Lee, Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
Kabsoo Shin, Eun-Kyo Jung, Se Jun Park, Sangwoon Jeong, In-Ho Kim, Myung-ah Lee, Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
Author contributions: Shin K and Kim IH designed the research and study concept; Park SJ and Jung EK performed the data collection; Shin K and Jeong S performed the statistical analysis; Shin K and Kim IH performed the data interpretation; Shin K drafted the manuscript; Lee MA revised the manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committees of The Institutional Review Board of the Catholic University of Seoul Saint Mary’s Hospital (approval No. KC20RASI0321).
Informed consent statement: The requirement for informed consent was waived because the study was based on retrospective analyses of existing administrative and clinical data.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
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: Myung-ah Lee, MD, PhD, Professor, Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Secho-gu, Seoul 06591, South Korea. angelamd@catholic.ac.kr
Received: February 24, 2021 Peer-review started: February 24, 2021 First decision: April 19, 2021 Revised: May 3, 2021 Accepted: July 9, 2021 Article in press: July 9, 2021 Published online: August 15, 2021
Abstract
BACKGROUND
A decline in serum carbohydrate antigen 19-9 (CA19-9) levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer. Neutrophil-to-lymphocyte ratio (NLR) has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer.
AIM
To assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity.
METHODS
We retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St. Mary’s Hospital. Patients were divided according to CA19-9 positivity (CA19-9-positive vs -negative groups) and pre-and post-treatment NLR levels. To determine cut-off value of NLR and CA19-9 reduction, time-dependent receiver operating characteristic curve was applied. We evaluated overall survival (OS) and progression-free survival (PFS) for each group using Kaplan-Meier method, and we performed multivariate analyses on the entire cohort.
RESULTS
We included 271 patients in this study. Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%. Multivariate analysis showed that post-treatment NLR < 2.62 and reduction of ≥ 18% of baseline CA19-9 were significantly associated with OS and PFS. Post-treatment NLR ≥ 2.62 showed hazard ratio (HR) of 2.47 [95% confidence interval (CI): 1.84-3.32, P < 0.001] and CA19-9 decline (≥ 18%) showed HR of 0.51 (95%CI: 0.39-0.67, P < 0.001) for OS. When CA19-9-positive patients were divided into groups according to CA19-9 response (responder vs non-responder) and post-treatment NLR (< 2.62 vs ≥ 2.62), CA19-9 responder and post-treatment NLR < 2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR ≥ 2.62 group (OS 11.0 mo vs 3.9 mo, P < 0.001; PFS 6.3 mo vs 2.0 mo, P < 0.001). The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group. Within the CA19-9-negative group, the post-treatment NLR < 2.62 group showed better survival than the post-treatment NLR ≥ 2.62 group (OS 12.7 mo vs 7.7 mo, P < 0.001; PFS 6.7 mo vs 2.1 mo, P < 0.001), and post-treatment NLR showed correlation with clinical response.
CONCLUSION
In advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy, the combination of post-treatment NLR < 2.62 and 18% decline of CA19-9 at the first response evaluation is a good prognostic marker. Post-treatment NLR < 2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.
Core Tip: In pancreatic cancer patients treated with first-line chemotherapy, carbohydrate antigen 19-9 (CA19-9) decline is considered as a prognostic marker. However, there has been no consensus regarding the degree of CA19-9 decline, and certain populations show false negativity. We evaluated the cut-off value of decline of CA19-9 and post-treatment neutrophil-to-lymphocyte ratio (NLR) as prognostic makers. Combination of post-treatment NLR (< 2.62) and decline of CA19-9 (≥ 18%) for CA19-9 positive group or post-treatment NLR alone for CA19-9 negative group could be used as a prognostic marker and an adjuvant tool for response evaluation.
