[Analysis of the safety and efficacy of neoadjuvant immunotherapy combined with chemotherapy for radical resection of locally advanced gastric cancer: a two-center propensity-matched study].

Objective: To investigate the impact of neoadjuvant immunotherapy combined with chemotherapy on the safety and efficacy of radical resection in patients with cT3-4NxM0 gastric cancer. Methods: A retrospective cohort study method was used. The clinicopathological data of 515 patients who underwent radical gastrectomy after neoadjuvant treatment at Second Department of Gastric Surgery,Fudan University Shanghai Cancer Center and Department of Gastric Surgery,Zhangzhou Hospital Affiliated to Fujian Medical University from January 2020 to June 2023 were collected. Among them,379 patients received neoadjuvant chemotherapy alone(chemotherapy group),and 136 patients received neoadjuvant immunotherapy combined with chemotherapy(immunotherapy group). There were 382 males and 133 females,with an age of (58.4±10.9)years(range:26 to 85 years). To reduce the influence of potential confounding factors,a 1∶1 propensity score matching method was adopted,and the clamp value was 0.02. The peri-operative safety,imaging and postoperative pathological tumor regression,and prognosis were compared by independent sample t-test, Mann-Whitney U test, χ² test or Fisher exact probability method between the two groups. The Kaplan-Meier method was used to draw survival curves, and the differences between groups were compared by Log-rank test. Results: After matching, there were 101 patients in each of the chemotherapy group and the immunotherapy group. The baseline data of the patients in the two groups were evenly distributed (all P>0.05). According to the RECIST 1.1 criteria, the complete response rate (11.9% (12/101) vs. 4.0% (4/101)), partial response rate(68.3%(69/101) vs. 53.4%(54/101)), stable disease rate (17.8%(18/101) vs. 39.6%(40/101)) and disease progression rate (2.0%(2/101) vs. 3.0%(3/101)) between the immunotherapy group and the chemotherapy group were no statistical defferences (χ²=14.374,P=0.002), and objective response rate (80.2%(81/101) vs. 57.4%(58/101), χ²=12.203, P<0.01) in the immunotherapy group was higher than that in the chemotherapy group. The results of postoperative pathological examination showed that the immunotherapy group had a higher complete response rate (16.8%(17/101) vs. 6.9% (7/101), χ²=4.728, P=0.030) and major pathological response rate (42.6%(43/101) vs. 23.8% (24/101), χ²=8.062, P=0.005). For the two groups, the operation time (175.0(76.0)minutes vs. 160.0 (30.0)minutes, Z=-0.059, P=0.953), intraoperative blood loss (110.0 (150.0)ml vs. 100.0 (120.0)ml, Z=-0.370, P=0.712), overall incidence of postoperative complications (20.8%(21/101) vs. 18.8%(19/101), χ²=0.125, P=0.724) and incidence of severe complications (5.0%(5/101) vs. 3.0%(3/101), χ²=0.130,P=0.718) were comparable. The median follow-up time of all patients was 46 months(range: 19 to 61 months). The 3-year overall survival rate (63.2% vs. 54.4%, P=0.035) and progression-free survival rate (59.1% vs. 45.6%, P=0.022) of the immunotherapy group were higher than those of the chemotherapy group. Meanwhile, there were no statistically significant differences in the incidence of neoadjuvant-treatment-related adverse events (48.5%(49/101) vs. 40.6% (41/101), χ²=1.283, P=0.411) and the incidence of severe adverse reactions of grade 3 or above (13.9% (14/101) vs. 10.9% (11/101), χ²=0.257, P=0.522) between the two groups. Conclusion: Neoadjuvant immunotherapy combined with chemotherapy can significantly improve the imaging and postoperative pathological tumor response rates and 3-year survival rate of patients with locally advanced gastric cancer,without increasing the incidence of postoperative complications and neoadjuvant treatment-related adverse event.