Optimizing Clinical Practice and Efficacy Evaluation of Radiotherapy Combined with Immunotherapy in Recurrent Esophageal Cancer: A Retrospective Cohort Study Focusing on Patient-Reported Pain Relief and Tumor Proliferation Inhibition

Objective: To evaluate the clinical efficacy and safety of radiotherapy combined with immunotherapy in patients with recurrent esophageal cancer, with a focus on patient-reported pain relief and changes in tumor proliferation-related biomarkers. Methods: This retrospective observational cohort study included 70 patients with recurrent esophageal cancer treated at a single center between February 2022 and June 2024. The primary endpoints were changes in patient-reported pain assessed using the Visual Analog Scale at baseline, 3 weeks, and 6 weeks, and alterations in tumor proliferation-related biomarkers. Secondary endpoints included clinical response, immune cell subsets, serum tumor markers, and treatment-related adverse events. Statistical analyses were performed using independent-samples t tests, chi-square tests, and repeated-measures analysis of variance. A two-sided P value < 0.05 was considered statistically significant. Results: Baseline characteristics and pain scores were comparable between groups. Repeated-measures analysis of variance demonstrated significant effects of group, time, and group–time interaction on pain scores (all P< 0.05), with greater pain reduction at 3 and 6 weeks in the radiotherapy plus immunotherapy group. The combination therapy group showed higher overall response and disease control rates than the radiotherapy-alone group. After treatment, reductions in vascular endothelial growth factor, matrix metalloproteinase-9, Yin Yang 1, carbohydrate antigen 125, carcinoembryonic antigen, and squamous cell carcinoma antigen were observed in both groups, with more pronounced decreases in the combination therapy group. Immune profiling revealed greater increases in cluster of differentiation 3-positive and cluster of differentiation 4-positive cells and a greater reduction in cluster of differentiation 8-positive cells following combination therapy. The incidence of treatment-related adverse events, including immune-related toxicities, was comparable between groups. Conclusion: In this retrospective observational study, radiotherapy combined with immunotherapy was associated with improved pain control and reductions in tumor proliferation-related biomarkers without an apparent increase in toxicity. These findings reflect associations and require confirmation in larger prospective studies. Keywords: radiotherapy, immunotherapy, recurrent esophageal cancer, pain, tumor proliferation