The Prognostic Role of Systemic Inflammatory Response Index in Surgically Treated Pancreatic Ductal Adenocarcinoma Patients

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy despite advances in treatment. The systemic inflammatory response index (SIRI), a composite marker of neutrophils, monocytes, and lymphocytes, has been proposed as a prognostic biomarker in various cancers. However, its role in resectable PDAC is not well established. Methods: This retrospective study analyzed 82 patients who underwent curative-intent surgery for PDAC between 2011 and 2021. Preoperative SIRI was calculated as (neutrophils × monocytes) / lymphocytes using blood counts obtained within one week before surgery. The optimal SIRI cut-off for overall survival (OS) prediction was determined using ROC analysis. Survival outcomes were assessed via Kaplan-Meier curves and Cox regression models. Results: The optimal SIRI cut-off was 1.36 (AUC: 0.738). Patients with SIRI ≤1.36 had significantly longer OS than those with SIRI >1.36 (42 vs. 22 months, p=0.013), including among early-stage patients. In multivariate analysis, SIRI >1.36 remained an independent predictor of poor OS (HR: 1.87, 95% CI: 1.08–3.21, p=0.023), along with age, ECOG status, and disease stage. Conclusions: Preoperative SIRI is an independent prognostic marker in resectable PDAC and may help identify high-risk patients who could benefit from intensified follow-up or additional therapeutic strategies. Prospective multicenter studies are warranted to validate these findings and integrate SIRI into clinical risk models.

Keywords

• pancreatic ductal adenocarcinoma(PDAC), systemic inflammatory response index(SIRI),
• prognostic factor
• overall survival

The Prognostic Role of Systemic Inflammatory Response Index in Surgically Treated Pancreatic Ductal Adenocarcinoma Patients

Abstract

References

1. Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A: Cancer statistics, 2025. CA: A Cancer Journal for Clinicians 2025;75:10-45.
2. Rawla P, Sunkara T, Gaduputi V: Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World journal of Oncology 2019; 10:10.
3. Groot VP, Gemenetzis G, Blair AB, Rivero-Soto RJ, Yu J, Javed AA, Burkhart RA, Rinkes I, Molenaar IQ, Cameron JL, et al: Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma. Ann Surg 2019;269:1154-1162.
4. Grivennikov SI, Greten FR, Karin M: Immunity, inflammation, and cancer. Cell 2010;140:883-899.
5. Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, Leibowitz-Amit R, Sonpavde G, Knox JJ, Tran B: Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Journal of the National Cancer Institute 2014;106:dju124.
6. Proctor M, McMillan D, Morrison D, Fletcher C, Horgan P, Clarke S: A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. British journal of cancer 2012;107:695-699.
7. Qi Q, Zhuang L, Shen Y, Geng Y, Yu S, Chen H, Liu L, Meng Z, Wang P, Chen Z: A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy. Cancer 2016;122:2158-2167.
8. Tang C, Zhang M, Jia H, Wang T, Wu H, Xu K, Ren T, Liang L: The systemic inflammation response index (SIRI) predicts survival in advanced non-small cell lung cancer patients undergoing immunotherapy and the construction of a nomogram model. Front Immunol 2024; 15:1516737.

9. Wu Q, Zhao H: Prognostic and clinicopathological role of pretreatment systemic inflammation response index (SIRI) in gastric cancer: a systematic review and meta-analysis. World J Surg Oncol 2024;22:333.
10. Xu L, Yu S, Zhuang L, Wang P, Shen Y, Lin J, Meng Z: Systemic inflammation response index (SIRI) predicts prognosis in hepatocellular carcinoma patients. Oncotarget 2017;8:34954-34960.
11. Ding Y, Liu Z, Li J, Niu W, Li C, Yu B: Predictive effect of the systemic inflammation response index (SIRI) on the efficacy and prognosis of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. BMC Surg 2024; 24:89.
12. Kim JS, Choi M, Kim SH, Hwang HK, Lee WJ, Kang CM: Systemic inflammation response index correlates with survival and predicts oncological outcome of resected pancreatic cancer following neoadjuvant chemotherapy. Pancreatology 2022; 22:987-993.
13. Joyce JA, Pollard JW: Microenvironmental regulation of metastasis. Nature Reviews Cancer 2009;9:239-252.
14. Egeblad M, Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nature Reviews Cancer 2002;2:161-174.
15. Chanmee T, Ontong P, Konno K, Itano N: Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment. Cancers 2014;6:1670-1690.
16. Man YG, Stojadinovic A, Mason J, Avital I, Bilchik A, Bruecher B, Protic M, Nissan A, Izadjoo M, Zhang X, Jewett A: Tumor-infiltrating immune cells promoting tumor invasion and metastasis: existing theories. J Cancer 2013;4:84-95.
17. Jin Y, Christenson ES, Zheng L, Li K: Neutrophils in pancreatic ductal adenocarcinoma: bridging preclinical insights to clinical prospects for improved therapeutic strategies. Expert Review of Clinical Immunology 2024;20:945-958.
18. Kiryu S, Ito Z, Suka M, Bito T, Kan S, Uchiyama K, Saruta M, Hata T, Takano Y, Fujioka S, et al: Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma. BMC Cancer 2021; 21:1197.
19. Li S, Xu H, Wang W, Gao H, Li H, Zhang S, Xu J, Zhang W, Xu S, Li T, et al: The systemic inflammation response index predicts survival and recurrence in patients with resectable pancreatic ductal adenocarcinoma. Cancer Manag Res 2019;11:3327-3337.
20. Shen H, Zuo F: Prognostic role of systemic inflammation response index (SIRI) in patients with pancreatic cancer: a meta-analysis. Front Oncol 2024;14:1465279.
21. Niu Z-h, Lin L, Peng H-y, Zheng X-z, Wang M-y, Sun F-x, Xu C-j: The prognostic value of systemic inflammation response index in digestive system carcinomas: a systematic review and meta-analysis. BMC Gastroenterology 2025;25:34.
22. Pacheco-Barcia V, Mondéjar Solís R, France T, Asselah J, Donnay O, Zogopoulos G, Bouganim N, Guo K, Rogado J, Martin E, et al: A systemic inflammation response index (SIRI) correlates with survival and predicts oncological outcome for mFOLFIRINOX therapy in metastatic pancreatic cancer. Pancreatology 2020;20:254-264.
23. Dâmaso S, Paiva R, Pinho I, Esperança-Martins M, Lopes Brás R, Melo Alvim C, Quintela A, Lúcia Costa A, Costa L: Systemic inflammatory response index is a prognostic biomarker in unresectable pancreatic adenocarcinoma and identifies patients for more intensive treatment. memo- Magazine of European Medical Oncology 2022;15:246-252.