[Efficacy and safety of combination immunotherapy for locally advanced esophageal carcinoma]

Objective: To investigate the efficacy and safety of combination immunotherapy in patients with locally advanced esophageal cancer. Methods: Clinical data of 212 patients with pathologically confirmed locally advanced esophageal cancer who received definitive chemoradiotherapy without surgery at the Affiliated Cancer Hospital of Xinjiang Medical University from January 2019 to January 2024 were retrospectively collected. Follow-up ended in January 2025. Patients were divided into an immunotherapy group (IO group, n=93) and a non-immunotherapy group (Non-IO group, n=119) based on whether immune checkpoint inhibitors were combined during treatment. Propensity score matching (PSM) was used to balance intergroup differences. Cox proportional hazards regression models were applied to identify independent factors influencing progression-free survival (PFS) and overall survival (OS). Results: Before PSM, among the 212 patients, the median PFS was not reached in the IO group, while it was 27.40 months in the Non-IO group. The 1-year PFS rate was significantly better in the IO group than in the Non-IO group (82.4% vs 72.3%; HR=0.65, P=0.048). The median OS was 37.37 months in the IO group and 30.17 months in the Non-IO group, with no statistically significant difference in 1-year OS rates (86.2% vs 82.6%; HR=0.66, P=0.064). After PSM, the median PFS remained unreached in the IO group (n=68), while it was 18.43 months in the Non-IO group (n=68). The IO group maintained its advantage in 1-year PFS rate (80.6% vs 73.7%; HR=0.53, P=0.017). Regarding OS, the median OS was 37.37 months in the IO group and 30.17 months in the Non-IO group, with 1-year OS rates of 84.5% and 90.8%, respectively; the difference was not statistically significant (HR=0.74, P=0.261). Multivariable analysis showed that combination immunotherapy was associated with better PFS (HR=0.49, P=0.010), but no association with OS was observed (HR=0.68, P=0.187). Additionally, N stage and smoking status were independent factors for PFS. Compared with squamous cell carcinoma, patients with non-squamous cell carcinoma had worse OS (HR=4.33, P=0.018). In terms of safety, there were no statistically significant differences between the IO group (n=68) and the Non-IO group (n=68) in the incidence of any-grade adverse events or grade ≥3 adverse events (all P＞0.05). However, the incidence of grade ≥3 lymphocytopenia was significantly higher in the IO group than in the Non-IO group (42.6% vs 19.1%; χ²=8.82, P=0.003). Conclusion: Compared with chemoradiotherapy alone, chemoradiotherapy combined with immunotherapy improves PFS in patients with locally advanced esophageal cancer, but is associated with a higher proportion of patients with severe lymphocytopenia.