Early Changes in the Neutrophil-to-Lymphocyte Ratio are Associated with Conversion Outcomes in Advanced Hepatocellular Carcinoma Treated with HAIC-Based Triple Therapy.

Abstract

Background: Reliable early biomarkers for identifying conversion potential during HAIC-based triple therapy in advanced unresectable hepatocellular carcinoma (uHCC) remain lacking. This study evaluated the predictive value of dynamic systemic inflammatory remodeling during treatment.

Methods: In this single-center retrospective cohort study, we included 296 patients with advanced uHCC treated with hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors and immune checkpoint inhibitors. Patients were stratified according to conversion status. ΔNLR was calculated as the NLR measured after the first treatment cycle minus the baseline NLR. Predictors for conversion were identified using logistic regression and evaluated via receiver operating characteristic analysis. A predictive nomogram was subsequently constructed and validated using calibration and decision curve analyses.

Results: Among 296 patients, 125 (42.2%) achieved successful conversion resection. Baseline NLR showed minimal predictive value for conversion (AUC = 0.501), whereas ΔNLR demonstrated significantly improved predictive performance (AUC = 0.819). The optimal cohort-derived cutoff was ΔNLR ≤ 0.20, with a sensitivity of 72.0% and a specificity of 91.8%. Multivariate analysis showed that higher ΔNLR was independently associated with lower odds of successful conversion (OR = 0.415, 95% CI: 0.328-0.524, P < 0.001). Patients in the conversion group achieved significantly improved tumor responses, overall survival, and progression-free survival. The nomogram incorporating ΔNLR demonstrated good calibration and clinical utility.

Conclusion: Lower ΔNLR values after one treatment cycle were associated with successful conversion resection during HAIC-based triple therapy for advanced uHCC. ΔNLR may serve as a candidate early marker of conversion potential, pending prospective external validation.