Precision Prognostic Modeling in Laryngeal Carcinoma: Construction and Validation of Genomic-Clinicopathologic Nomograms in a Multi-Center Cohort

Objectives.: This study aimed to develop nomograms for predicting overall survival (OS) and disease-free survival (DFS) in patients with laryngeal squamous cell carcinoma (LSCC) using a costeffective targeted next-generation sequencing (tNGS) panel integrating with genomic and clinicopathological features in order to provide a concrete decision-support tool improve individualized prognostic assessment. Methods.: A total of 124 LSCC patients from a multi-center cohort were analyzed using a targeted sequencing panel covering 113 cancer-associated genes. Single nucleotide variants/Insertiondeletions (SNVs/Indels) and Copy number variants (CNVs) were identified and correlated with survival outcomes. Kaplan-Meier analysis and Cox regression were performed to select significant prognostic markers. Nomograms incorporating genetic and clinical variables were developed, and their predictive performance was evaluated using the receiver operating characteristic (ROC) curves, and calibration curves. Results.: The LSCC Mutation (SNVs/Indels) and CNV panels were constructed based on genes with high mutational frequencies in tNGS and prognostic significance. In multivariable analysis, age, maximum tumor diameter, and the LSCC Mutation Panel were independent predictors of OS, while maximum tumor diameter and the LSCC DFS Mutation Panel were predictive of DFS. Both models demonstrated good calibration and discrimination. Conclusion.: This study developed genomic-clinicopathologic nomograms for predicting LSCC prognosis, providing a precise, cost-effective and clinically feasible tool for personalized survival assessment.