Clinical value of change of systemic immune inflammation index before and after neoadjuvant chemotherapy on prognosis of patients with advanced pancreatic cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHU Lei ¹ , GU Hongzhu ¹ , LI Shanshan ² ,  WANG Yang ³

1. Department of General Surgery, Panjin Liao-Oil Gem Flower Hospital, Panjin, Liaoning 124010, P. R. China;
2. Department of Medicine, Panjin Liao-Oil Gem Flower Hospital, Panjin, Liaoning 124010, P. R. China;
3. Department of Oncology Surgery, Panjin Liao-Oil Gem Flower Hospital, Panjin, Liaoning 124010, P. R. China;

Corresponding author：

WANG Yang, Email: 402390989@qq.com

Keywords：

pancreatic cancer; systemic immune inflammatory index; prognosis

DOI：

10.7507/1007-9424.202004037

Video：

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Objective To determine the prognostic significance of change of systemic immune inflammation index (SII) before and after neoadjuvant chemotherapy (NCT) in advanced pancreatic cancer.Methods The patients with advanced pancreatic cancer who received the NCT before pancreatectomy and met the inclusion and exclusion criteria of this study from January 2013 to December 2016 in the Panjin Liao-Oil Gem Flower Hospital were retrospectively collected. The patients were designed into an increased SII group (SII before NCT was lower than after NCT) and decreased SII group (SII before NCT was higher than after NCT) according to the change of SII before and after NCT. The laboratory data before and after NCT were collected to calculate the SII and to analyze the relationship between the change of SII before and after NCT and the clinical outcomes. The clinicopathologic characteristics and postoperative 3-year survival rate of the two groups were compared. The Cox regression was used to evaluate the influencing factors of postoperative survival of advanced pancreatic cancer.Results All of 103 patients were included, 42 of whom in the increased SII group and 61 in the decreased SII group. The proportions of the intraoperative tumor size >3 cm, CA19-9>37 U/mL after NCT, and postoperative complications in the increased SII group were significantly higher than those in the decreased SII group (P<0.05). All 103 patients were followed up from 9 to 81 months with median 13 months, the 3-year cumulative survival rate of patients in the increased SII group was significantly lower than that of patients in the decreased SII group (19.0% versus 42.6%, P=0.012). The results of the multivariate analysis showed that the CA19-9>37 U/mL after NCT [HR=2.084, 95%CI (1.140, 3.809), P=0.017], postoperative complications [HR=1.657, 95%CI (1.009, 2.722), P=0.046], the absent of postoperative adjuvant chemotherapy [HR=1.795, 95%CI (1.085, 2.970), P=0.023], and the elevated SII after NCT [HR=1.849, 95%CI (1.111, 3.075), P=0.018] were the independent risk factors affecting postoperative 3-year survival rate of patients with advanced pancreatic cancer.Conclusions The change value of SII before and after NCT is an independent risk factor for the prognosis of patient with advanced pancreatic cancer, the elevated SII after NCT is a poor prognosis index in patient with advanced pancreatic cancer. However, the evaluations of larger controlled trials are necessary at multiple institutions before introduction of SII as a prognostic indicator in clinical practice.

Citation： ZHU Lei, GU Hongzhu, LI Shanshan, WANG Yang. Clinical value of change of systemic immune inflammation index before and after neoadjuvant chemotherapy on prognosis of patients with advanced pancreatic cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(1): 12-17. doi: 10.7507/1007-9424.202004037 Copy

1.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin, 2020, 70(1): 7-30.
2.	Aier I, Semwal R, Sharma A, et al. A systematic assessment of statistics, risk factors, and underlying features involved in pancreatic cancer. Cancer Epidemiol, 2019, 58: 104-110.
3.	Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res, 2014, 74(11): 2913-2921.
4.	Canto MI, Almario JA, Schulick RD, et al. Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance. Gastroenterology, 2018, 155(3): 740-751.
5.	Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
6.	Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg, 2015, 261(1): 12-17.
7.	Mokdad AA, Minter RM, Zhu H, et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis. J Clin Oncol, 2017, 35(5): 515-522.
8.	Wagner M, Antunes C, Pietrasz D, et al. CT evaluation after neoadjuvant FOLFIRINOX chemotherapy for borderline and locally advanced pancreatic adenocarcinoma. Eur Radiol, 2017, 27(7): 3104-3116.
9.	Kluger MD, Rashid MF, Rosario VL, et al. Resection of locally advanced pancreatic cancer without regression of arterial encasement after modern-era neoadjuvant therapy. J Gastrointest Surg, 2018, 22(2): 235-241.
10.	Cassinotto C, Sa-Cunha A, Trillaud H. Radiological evaluation of response to neoadjuvant treatment in pancreatic cancer. Diagn Interv Imaging, 2016, 97(12): 1225-1232.
11.	Boone BA, Steve J, Zenati MS, et al. Serum CA19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol, 2014, 21(13): 4351-4358.
12.	Rieser CJ, Zenati M, Hamad A, et al. CA19-9 on postoperative surveillance in pancreatic ductal adenocarcinoma: predicting recurrence and changing prognosis over time. Ann Surg Oncol, 2018, 25(12): 3483-3491.
13.	Haab BB, Huang Y, Balasenthil S, et al. Definitive characterization of CA19-9 in resectable pancreatic cancer using a reference set of serum and plasma specimens. PLoS One, 2015, 10(10): e0139049.
14.	Hausmann S, Kong B, Michalski C, et al. The role of inflammation in pancreatic cancer. Adv Exp Med Biol, 2014, 816: 129-151.
15.	Aziz MH, Sideras K, Aziz NA, et al. The systemic-immune-inflammation index independently predicts survival and recurrence in resectable pancreatic cancer and its prognostic value depends on bilirubin levels: a retrospective multicenter cohort study. Ann Surg, 2019, 270(1): 139-146.
16.	Jomrich G, Gruber ES, Winkler D, et al. Systemic immune-inflammation index (SII) predicts poor survival in pancreatic cancer patients undergoing resection. J Gastrointest Surg, 2020, 24(3): 610-618.
17.	Masui T, Doi R, Kawaguchi Y, et al. Concurrent gemcitabine+S-1 neoadjuvant chemotherapy contributes to the improved survival of patients with small borderline-resectable pancreatic cancer tumors. Surg Today, 2016, 46(11): 1282-1289.
18.	Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin, 2017, 67(2): 93-99.
19.	Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg, 2009, 250(2): 187-196.
20.	Thanikachalam K, Damarla V, Seixas T, et al. Neoadjuvant phase Ⅱ trial of chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer. Am J Clin Oncol, 2020, 43(6): 435-441.
21.	Zhan HX, Xu JW, Wu D, et al. Neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of prospective studies. Cancer Med, 2017, 6(6): 1201-1219.
22.	Tempero MA, Malafa MP, Chiorean EG, et al. Pancreatic adenocarcinoma, version 1.2019. J Natl Compr Canc Netw, 2019, 17(3): 202-210.
23.	Epelboym I, Zenati MS, Hamad A, et al. Analysis of perioperative chemotherapy in resected pancreatic cancer: identifying the number and sequence of chemotherapy cycles needed to optimize survival. Ann Surg Oncol, 2017, 24(9): 2744-2751.
24.	Kirkegård J, Mortensen FV, Cronin-Fenton D. Chronic pancreatitis and pancreatic cancer risk: a systematic review and meta-analysis. Am J Gastroenterol, 2017, 112(9): 1366-1372.
25.	Zhong JH, Huang DH, Chen ZY. Prognostic role of systemic immune-inflammation index in solid tumors: a systematic review and meta-analysis. Oncotarget, 2017, 8(43): 75381-75388.
26.	Zhang K, Hua YQ, Wang D, et al. Systemic immune-inflammation index predicts prognosis of patients with advanced pancreatic cancer. J Transl Med, 2019, 17(1): 30.
27.	Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer, 2016, 16(7): 431-446.
28.	Padoan A, Plebani M, Basso D. Inflammation and pancreatic cancer: focus on metabolism, cytokines, and immunity. Int J Mol Sci, 2019, 20(3): E676.
29.	Boone BA, Zenati MS, Rieser C, et al. Risk of venous thromboembolism for patients with pancreatic ductal adenocarcinoma undergoing preoperative chemotherapy followed by surgical resection. Ann Surg Oncol, 2019, 26(5): 1503-1511.
30.	Meikle CK, Kelly CA, Garg P, et al. Cancer and thrombosis: the platelet perspective. Front Cell Dev Biol, 2017, 4: 147.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin, 2020, 70(1): 7-30.
2. Aier I, Semwal R, Sharma A, et al. A systematic assessment of statistics, risk factors, and underlying features involved in pancreatic cancer. Cancer Epidemiol, 2019, 58: 104-110.
3. Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res, 2014, 74(11): 2913-2921.
4. Canto MI, Almario JA, Schulick RD, et al. Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance. Gastroenterology, 2018, 155(3): 740-751.
5. Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
6. Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg, 2015, 261(1): 12-17.
7. Mokdad AA, Minter RM, Zhu H, et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis. J Clin Oncol, 2017, 35(5): 515-522.
8. Wagner M, Antunes C, Pietrasz D, et al. CT evaluation after neoadjuvant FOLFIRINOX chemotherapy for borderline and locally advanced pancreatic adenocarcinoma. Eur Radiol, 2017, 27(7): 3104-3116.
9. Kluger MD, Rashid MF, Rosario VL, et al. Resection of locally advanced pancreatic cancer without regression of arterial encasement after modern-era neoadjuvant therapy. J Gastrointest Surg, 2018, 22(2): 235-241.
10. Cassinotto C, Sa-Cunha A, Trillaud H. Radiological evaluation of response to neoadjuvant treatment in pancreatic cancer. Diagn Interv Imaging, 2016, 97(12): 1225-1232.
11. Boone BA, Steve J, Zenati MS, et al. Serum CA19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol, 2014, 21(13): 4351-4358.
12. Rieser CJ, Zenati M, Hamad A, et al. CA19-9 on postoperative surveillance in pancreatic ductal adenocarcinoma: predicting recurrence and changing prognosis over time. Ann Surg Oncol, 2018, 25(12): 3483-3491.
13. Haab BB, Huang Y, Balasenthil S, et al. Definitive characterization of CA19-9 in resectable pancreatic cancer using a reference set of serum and plasma specimens. PLoS One, 2015, 10(10): e0139049.
14. Hausmann S, Kong B, Michalski C, et al. The role of inflammation in pancreatic cancer. Adv Exp Med Biol, 2014, 816: 129-151.
15. Aziz MH, Sideras K, Aziz NA, et al. The systemic-immune-inflammation index independently predicts survival and recurrence in resectable pancreatic cancer and its prognostic value depends on bilirubin levels: a retrospective multicenter cohort study. Ann Surg, 2019, 270(1): 139-146.
16. Jomrich G, Gruber ES, Winkler D, et al. Systemic immune-inflammation index (SII) predicts poor survival in pancreatic cancer patients undergoing resection. J Gastrointest Surg, 2020, 24(3): 610-618.
17. Masui T, Doi R, Kawaguchi Y, et al. Concurrent gemcitabine+S-1 neoadjuvant chemotherapy contributes to the improved survival of patients with small borderline-resectable pancreatic cancer tumors. Surg Today, 2016, 46(11): 1282-1289.
18. Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin, 2017, 67(2): 93-99.
19. Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg, 2009, 250(2): 187-196.
20. Thanikachalam K, Damarla V, Seixas T, et al. Neoadjuvant phase Ⅱ trial of chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer. Am J Clin Oncol, 2020, 43(6): 435-441.
21. Zhan HX, Xu JW, Wu D, et al. Neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of prospective studies. Cancer Med, 2017, 6(6): 1201-1219.
22. Tempero MA, Malafa MP, Chiorean EG, et al. Pancreatic adenocarcinoma, version 1.2019. J Natl Compr Canc Netw, 2019, 17(3): 202-210.
23. Epelboym I, Zenati MS, Hamad A, et al. Analysis of perioperative chemotherapy in resected pancreatic cancer: identifying the number and sequence of chemotherapy cycles needed to optimize survival. Ann Surg Oncol, 2017, 24(9): 2744-2751.
24. Kirkegård J, Mortensen FV, Cronin-Fenton D. Chronic pancreatitis and pancreatic cancer risk: a systematic review and meta-analysis. Am J Gastroenterol, 2017, 112(9): 1366-1372.
25. Zhong JH, Huang DH, Chen ZY. Prognostic role of systemic immune-inflammation index in solid tumors: a systematic review and meta-analysis. Oncotarget, 2017, 8(43): 75381-75388.
26. Zhang K, Hua YQ, Wang D, et al. Systemic immune-inflammation index predicts prognosis of patients with advanced pancreatic cancer. J Transl Med, 2019, 17(1): 30.
27. Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer, 2016, 16(7): 431-446.
28. Padoan A, Plebani M, Basso D. Inflammation and pancreatic cancer: focus on metabolism, cytokines, and immunity. Int J Mol Sci, 2019, 20(3): E676.
29. Boone BA, Zenati MS, Rieser C, et al. Risk of venous thromboembolism for patients with pancreatic ductal adenocarcinoma undergoing preoperative chemotherapy followed by surgical resection. Ann Surg Oncol, 2019, 26(5): 1503-1511.
30. Meikle CK, Kelly CA, Garg P, et al. Cancer and thrombosis: the platelet perspective. Front Cell Dev Biol, 2017, 4: 147.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Clinical value of change of systemic immune inflammation index before and after neoadjuvant chemotherapy on prognosis of patients with advanced pancreatic cancer

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