Prognostic Significance Of Systemic Inflammatory Markers In Patients With Pancreatic Cancer

Objective: Systemic inflammatory markers are associated with the prognosis of multiple malignancies including Pancreatic Cancer(PC).The purpose of this study was to investigate the prognostic value of systemic immune inflammation index(SII)in patients with PC,and to analyze the prognostic value of platelet to lymphocyte ratio(PLR),neutrophil to lymphocyte ratio(NLR)and lymphocyte to monocyte ratio(LMR).Platelet-albumin-bilirubin(PALBI)grade is a comprehensive indicator based on liver function.Patients with pancreatic head cancer may have obstructive jaundice due to tumor infiltration or compression,which leads to abnormal liver function.Based on this,we also explored the prognostic value of PALBI grade in PC patients.Methods: A total of 457 patients with PC at the Affiliated Hospital of Qingdao University from January 2000 to December 2010 were retrospectively analysed and followed up by December 2020.The clinical data and laboratory examination indexes of patients without clinical intervention were collected.The values of various inflammatory markers were calculated according to the peripheral immune cell count,and the cut-off values were calculated by Youden index.The Kaplan Meier method was used to draw survival curves,and the differences between curves were analyzed by Log-Rank test.Univariate and multivariate analysis of prognostic factors was conducted by Cox proportional-hazards regression model,mainly the prognostic value of SII.The effect of PALBI grading on overall survival(OS)and disease free survival(DFS)in patients with pancreatic head cancer in radical surgery group were also discussed.In patients with metastatic and unresectable PC,the effects of various inflammatory markers on the OS were also explored,and further confirmed whether there was correlation between various inflammatory infactors for liver metastasis of PC.In order to reduce the selection bias of patients and eliminate some confounding factors,the propensity score matching(PSM)was used for analysis.The caliper value was taken as 0.1 to analyze the impact of SII on OS.Result:1.In the radical surgery group,a total of 214 patients(median age 60.29 years;128[59.8%] men)met the inclusion criteria,including 140 cases of pancreatic head cancer(65.4%).According to the Youden index,the patients were divided into high and low SII groups,high and low PALBI grade groups.The cut-off values were 705 and-5.6respectively.According to multivariate analysis,higher SII(HR,3.058;P < 0.001),lymph node metastasis(HR,2.814;P = 0.007),vascular invasion(HR,2.335;P = 0.010)and larger tumor size(HR,0.164;P = 0.004)were independently associated with OS.In addition,tumor size(HR,4.486;P=0.011),tumor location(HR,4.426;P<0.001),diabetes(HR,1.928;P=0.034),nerve invasion(HR,3.082;P=0.002)and lymph node metastasis(HR,2.738;P<0.001)were related to the DFS of PC.In patients with pancreatic head cancer,higher PALBI grade was associated with shorter OS(P = 0.031).The OS of high SII combined with high PALBI grade was significantly shorter than that of the two low groups,which had stronger predictive value for poor prognosis(log rank test,P < 0.001).2.In the metastatic and unresectable group,a total of 243 patients(median age 61.7years;152 [62.6%] men)met the inclusion criteria,of which 102(42.0%)had liver metastasis.The patients were divided into high SII group and low SII group,and the cut-off value was 533.High SII(HR,2.190;P < 0.001),distant metastasis(HR,1.776;P= 0.001),lymph node metastasis(HR,3.004,P < 0.001)and chemotherapy(HR,0.552,P = 0.036)were independent risk factors for OS.In addition,subgroup analysis of patients with liver metastasis and inflammatory markers was carried out.SII,PLR and NLR in patients with liver metastasis were significantly higher than those without liver metastasis.3.To further verify the effect of SII on the prognosis of patients with PC,PSM analysis was performed on all 457 patients.The patients were divided into high groop and low group accroding to the cut-off value of SII.The number of cases in the two groups were125 and 332 respectively.The patients were matched 1:2,and the caliper value was 0.1.Afer PSM,there were 113 and 182 in the two groups.The results showed that SII was an independent risk factor for OS in patients with PC before and after PSM(P<0.001).Conclusions:1.The OS and DFS of PC patients with high SII are shorter.2.PALBI grade was inversely proportional to the OS of patients with pancreatic head cancer undergoing radical surgery,and the combination of SII has better predictive value.3.Combination of SII and PLR can better predict the OS of patients with metastatic and unresectable PC.4.Patients with high levels of SII,NLR and PLR may be more likely to have early liver metastases,which provides a new method for early screening of PC.