Abstract:

Objective To analyze the efficacy and safety of concurrent radiotherapy combined with tegafur suppositories and immune checkpoint inhibitors in the treatment of elderly patients with esophageal cancer. Methods The clinical data of 52 elderly patients （aged ≥65 years） with unresectable esophageal squamous cell carcinoma who received concurrent chemoradiotherapy with or without immune checkpoint inhibitors in Cangzhou Central Hospital of Hebei Province from December 2019 to April 2025 were collected. According to whether the patients received immune checkpoint inhibitors during concurrent radiotherapy and tegafur suppository chemotherapy， they were divided into the concurrent chemoradiotherapy plus immunotherapy group [concurrent radiotherapy with tegafur suppositories combined with programmed death-1 （PD-1） inhibitors， tegafur suppositories combined with PD-1 inhibitors were administered for up to 2 years—or until disease progression， unacceptable toxicity， or patient withdrawal， n=27] and the concurrent chemoradiotherapy group （concurrent radiotherapy with tegafur suppositories， tegafur suppositories were administered for up to 2 years—or until disease progression， unacceptable toxicity， or patient withdrawal， n=25）. All patients underwent comprehensive reassessment 1-3 months after treatment completion to determine tumor response. The objective response rate （ORR）， progression-free survival （PFS）， overall survival （OS）， adverse reactions， etc. were analyzed and compared between the two groups. Survival outcomes were estimated using the Kaplan-Meier method and compared via log-rank tests. The Cox proportional risk regression model was performed to identify prognostic influencing factors. Results The ORR of the concurrent chemoradiotherapy plus immunotherapy group and the concurrent chemoradiotherapy group were 55.6% （15/27） and 24.0% （6/25）， respectively， with statistically significant difference （χ²=5.37， P=0.020）. The median PFS of the concurrent chemoradiotherapy plus immunotherapy group and the concurrent chemoradiotherapy group were 19.0 and 10.0 months， respectively； and the median OS were 33.3 months and 23.3 months， respectively， with statistically significant differences （χ²=10.60， P=0.001； χ²=5.10， P=0.024）. Univariate analysis revealed that Eastem Cooperative Oncology Group （ECOG） performance status （PS） score （HR=5.02， 95%CI： 2.40-10.53， P<0.001； HR=10.32， 95%CI： 3.55-30.04， P<0.001）， TNM stage （HR=6.14， 95%CI： 2.80-13.42， P<0.001； HR=5.93， 95%CI： 2.32-15.15， P<0.001）， and treatment modality （HR=0.36， 95%CI： 0.19-0.68， P=0.002； HR=0.39， 95%CI： 0.17-0.91， P=0.030） were influencing factors of both PFS and OS of patients. Multivariate analysis confirmed TNM stage （HR=5.65， 95%CI： 2.07-15.43， P=0.001） and treatment modality （HR=0.32， 95%CI： 0.16-0.64， P=0.001） as independent factors influencing PFS， and ECOG PS score （HR=5.31， 95%CI： 1.59-17.73， P=0.007） and TNM stage （HR=3.36， 95%CI： 1.10-10.29， P=0.034） as independent factors influencing OS. Adverse reactions of the two groups of patients were mainly radiation esophagitis， radiation pneumonitis， hematological toxicity， nausea/vomiting， etc. which were mostly grade 1-2， and resolved after symptomatic treatment or termination of treatment. The incidence rates of radiation pneumonitis were 51.9% （14/27） in the concurrent chemoradiotherapy plus immunotherapy group and 44.0% （11/25） in the concurrent chemoradiotherapy group， with no statistically significant difference （χ²=0.32， P=0.571）. Conclusions Concurrent radiotherapy combined with tegafur suppositories and immune checkpoint inhibitors demonstrates superior antitumor efficacy and acceptable safety in elderly patients with unresectable esophageal squamous cell carcinoma.

Key words: Aged, Esophageal neoplasms, Radiotherapy, Immunotherapy, Tegafur suppositories