The Efficacy And Prognosis Of SII And PNI In Patients With Advanced Gastric Cancer Treated With Immune Checkpoint Inhibitors

Background and Objective:Gastric cancer is the commonest malignancy of the gastrointestinal tract and is the third leading cause of cancer related deaths.Currently,most gastric cancers are detected at mid-to late-stage and have a poor prognosis.Chemotherapy,radiation therapy,and targeted therapy are important tools for the treatment of advanced gastric cancer,and with the breakthrough development of immunotherapy,It has evolved from recommended third-line and later applications to first-line benefits,and immunotherapy has become the standard treatment modality for advanced gastric cancer.At the same time,it has become more and more urgent to explore biomarkers to predict the efficacy of immunotherapy for tumors.Currently,the main predictive markers of immunotherapy for gastric cancer are PD-LI(Programmed cell death-ligand 1)expression level,microsatellite instability(MSI)or mismatch repair defect(dMMR),tumor mutational burden(TMB),EBV positivity,etc.With the understanding of tumor microenvironment,peripheral hematological indicators related to tumor microenvironment stand out due to their simplicity,accessibility and affordability,and more and more studies confirm the predictive role of peripheral hematological indicators in immunotherapy.For example,in the tumor microenvironment,neutrophil’s function and phenotype can be change and it can participate in different stages of the carcinogenic process,including tumor growth,invasion and metastasis,while tumor infiltrating CD4+and CD8+lymphocytes may have favorable effects on tumor suppressive properties,etc.In addition,the combined peripheral hematological indices such as neutrophil-to-lymphocyte ratio(NLR)and lymphocyte-to-monocyte ratio(LMR)have been suggested to be significant for the prognosis of immunotherapy in gastric cancer.while the systemic immune-inflammation index(SII)and prognostic nutritional index(PNI)have not been investigated for the prediction of immunotherapy in gastric cancer.This study retrospectively analyzed the impact of progression-free survival(PFS)with SII and PNI in patients with advanced gastric cancer treated with immune checkpoint inhibitors(ICIs)before immunotherapy,and provided a preliminary reference for clinical selection of the beneficiary population of immunotherapy in patients with advanced gastric cancer.Methods:Sixty-five patients with advanced gastric cancer treated with immune checkpoint inhibitors(ICIs)from January 1,2018,to May 30,2021,at Qingdao Municipal Hospital affiliated to Qingdao University were retrospectively analyzed.The patients’ blood Count and biochemical results and their related clinical data were collected within 1 week before treatment with ICIs.The differences in disease control rate(DCR)between the groups were examined separately by chi-square test;Survival analysis was conducted by Kaplan-Meier for univariate analysis,and Cox proportional risk regression model was used for multifactorial analysis.All data were analyzed with SPSS 26.0 software(SPSS Inc.,Chicago,IL,USA),and differences were regarded as statistically significant at P<0.05.Results:1.The DCR of SII in the high and low groups were 51.5%and 71.9%,respectively,and there was no correlation between SII level and DCR before treatment(P>0.05).The DCR of PNI in the high and low groups was 75.8%and 46.9%,respectively,and there was a correlation between PNI level and DCR(P<0.05).2.Patients in the high SII group with gastric cancer have a median progression-free survival(PFS)of 8 months,while the median PFS in the low SII group has not reached the study endpoint,Low SII predicted longer PFS in patients with advanced gastric cancer treated with ICIs.(Log-rank P=0.023);Patients in the high PNI group with gastric cancer has not reached the study endpoint,while the median PFS in the low SII group have a median PFS of 8 months,High PNI predicted longer PFS in patients with advanced gastric cancer treated with ICIs(Log-rank P=0.002).3.Univariate results showed that treatment regimen,PD-L1 expression level,SII,and PNI were correlated with patient PFS(P<0.05).The results of multifactorial analysis showed that SII and PNI were independent risk factors for PFS(P<0.05).Conclusions:SII and PNI can predict the efficacy and prognosis of immunotherapy in patients with advanced gastric cancer,and are expected to be new predictors in the future.