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The Role of Antinuclear Antibody in Predicting the Efficacy and Immune-Related Adverse Events of Immunochemotherapy in Esophageal Squamous Cell Carcinoma: A Real-World Analysis

Year: 2026

Type: article

Abstract: Background: Programmed cell death protein 1 (PD-1) inhibitor-based immunochemotherapy is a standard treatment for advanced esophageal squamous cell carcinoma (ESCC), but accessible blood-based biomarkers associated with both treatment efficacy and the risk of immune-related adverse events (irAEs) remain limited. The presence of antinuclear antibody (ANA) in the pretreatment period may reflect host immune status; however, its clinical relevance in ESCC and its relationship with programmed death-ligand 1 (PD-L1) expression have not been fully characterized. Methods: We retrospectively enrolled 180 patients with ESCC who received PD-1 inhibitor-based immunochemotherapy. Baseline characteristics, tumor responses, survival outcomes, and irAEs were evaluated according to pretreatment ANA status. An additional sensitivity analysis was conducted among 103 patients with available PD-L1 results. Cox regression models with time-varying coefficients were applied when the proportional hazards assumption was not satisfied. Results: The ANA-positive rate was 36.67% (66/180). Compared to patients who were ANA-negative, those who were ANA-positive demonstrated superior objective response rates (71.21% vs. 46.49%, p = 0.002), longer median progression-free survival (PFS; 11.93 vs. 5.93 months) and longer median overall survival (OS; 25.20 vs. 14.77 months, both p < 0.01). In addition, they had a higher rate of all-grade irAEs (60.61% vs. 35.96%, p = 0.001), especially thyroid dysfunction (28.79% vs. 8.77%, p < 0.001). Multivariable time-varying Cox models linked ANA positivity to favorable PFS (hazard ratio [HR] = 0.14, 95% confidence interval [CI]: 0.04–0.46, p = 0.001) and OS (HR = 0.06, 95% CI: 0.01–0.52, p = 0.011). In the sensitivity cohort, ANA remained predictive for both survival endpoints, while PD-L1 did not. Conclusions: Pretreatment ANA positivity was associated with higher response rates, longer survival, and a higher incidence of irAEs in patients with ESCC receiving PD-1 inhibitor-based immunochemotherapy. These exploratory findings require prospective validation before ANA can be used to guide treatment decisions or assess individual irAE risk.

Source: Current Oncology

DOI: 10.3390/curroncol33100596