Efficacy And Safety Of Immunotherapy Combined With Chemotherapy In Neoadjuvant Treatment For Locally Advanced Gastric Cancer

Objective:To investigate the short-term efficacy and safety of programmed death receptor-1(PD-1)inhibitors combined with oxaliplatin and S-1(SOX)regimens compared to chemotherapy alone in the neoadjuvant treatment of patients with locally progressive gastric cancer,and to explore predictors of neoadjuvant treatment efficacy.Methods:The clinical data of 114 patients with locally progressive gastric cancer admitted to the First Hospital of Lanzhou University from January 1,2020 to January31,2022 were retrospectively analyzed,and the patients were divided into PD-1inhibitor combined with SOX group(combined group,35 patients)and SOX group(control group,79 patients)according to the treatment regimen.In this study,we firstly compared the clinicopathological data such as age,gender and neoadjuvant treatment regimen between the two groups,and secondly analysed the efficacy of neoadjuvant treatment and whether the differences in adverse effects were statistically significant and statistical analysis of the surgical data was performed to observe the impact of neoadjuvant therapy on the safety of surgery.Finally,Chi-square tests and Logistic regression analyses were used to explore whether there was a correlation between clinicopathological data and the efficacy of neoadjuvant treatment,and to identify predictors of neoadjuvant efficacy.Results:The 114 patients enrolled were grouped and analysed.The statistical results of the patients’clinicopathological data showed that the proportion of patients with tumour site and clinical T-stage differed between the two groups,with a higher proportion of patients with tumours located in the gastric body and antrum of stomach and a lower proportion of patients with T-stage 4 in the combined group,with statistically significant differences(P<0.05),the remaining differences in clinicopathological features were not statistically significant(P>0.05).In terms of recent outcomes,the proportion of patients assessed to be in complete remission,major pathological remission and pathological complete remission after treatment in the combination group compared to the control group was 17.14%vs 3.79%(χ~2=4.247,P=0.039)and 28.57%vs 12.66%respectively(χ~2=4.246,P=0.039),20.00%vs6.33%(χ~2=4.813,P=0.028),all statistically significant differences;Objective remission rate between the two groups was 71.43%and 50.63%respectively(χ~2=4.280,P=0.039),a statistically significant difference,and disease control rate of 100%and 97.47%,respectively,a statistically insignificant difference.The reduction rate of N-stage was91.43%and 56.96%in the two groups(χ~2=13.143,P<0.001),a statistically significant difference;according to the different Programmed death ligand-1(PD-L1)expression levels of patients in the combined group stratified analysis of their recent efficacy resulted in no significant correlation between PD-L1 expression levels and the efficacy of neoadjuvant therapy.In terms of adverse reactions,there was no statistically significant difference in the incidence of overall adverse reactions and grade 3 adverse reactions between the combination group and the control group;among grade 1 to 2adverse reactions,the incidence of elevated transaminases was higher in the combination group and the difference was statistically significant(P<0.05);no grade 4adverse reactions or treatment-related deaths were observed in either group.In terms of surgical safety,the incidence of postoperative complications was similar in both groups,with the immune combination regimen not increasing the incidence of postoperative complications.Univariate analysis of neoadjuvant efficacy showed that age(P=0.007),Lauren staging(P=0.003),c T staging(P=0.007),c N staging(P=0.042),vascular involvement(P=0.004),and lymphatic vessel involvement(P<0.001)were factors influencing overall response rate,and c T staging(P=0.012),c N staging(P=0.014),vascular invasion(P=0.006),and lymphatic vessel invasion(P=0.001)were factors influencing the rate of primary pathological remission,and multifactorial analysis showed that age was an independent influence on the overall response rate,and no independent influences on the rate of primary pathological remission were identified.Conclusion:1.First-line use of immune checkpoint inhibitors in combination with chemotherapy as neoadjuvant therapy in patients with locally progressive gastric cancer had a more pronounced effect on tumour remission and stage reduction than chemotherapy alone.2.The adverse events associated with PD-1 inhibitor combination chemotherapy were generally manageable,well tolerated by patients,and did not significantly affect the safety of surgery.3.Age was an independent influence on the efficacy of neoadjuvant therapy,with patients aged≥55 years more likely to benefit from neoadjuvant therapy,and no significant correlation was observed between the efficacy of immunotherapy and the level of PD-L1 expression.