Exploring the Prognostic Value of EBV DNA in Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy Using AI-Based Modeling

Yang Yang¹Ningchuan Shang²Shun Lu³Lin tao Li³Fan Li⁴Peng Xu³Xian liang Wang³Yue Su³Yuan Qin³Jin yi Lang³Jie Zhou^3*

• ¹Department of Oncology, the Third People's Hospital of Chengdu, Chengdu, China
• ²School of Clinical Medicine, Sichuan College of Traditional Chinese Medicine, Mianyang, China
• ³Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital and Institute, Chengdu, China
• ⁴Chongqing University, Chongqing, China

Epstein-Barr virus (EBV) DNA is a well-established biomarker in nasopharyngeal carcinoma (NPC), but its integration into artificial intelligence (AI)-based prognostic tools remains limited. This study aimed to develop and validate AI models incorporating EBV DNA load levels to predict progression-free survival (PFS) in patients with advanced NPC treated with concurrent chemoradiotherapy (CRT).A retrospective multicenter cohort of 503 patients was divided into training (n = 301) and validation (n = 202) sets. Four machine learning algorithms-Cox regression, LASSO, RSF, and GBM-were applied to predict 1-and 1.5-year PFS in patients with advanced NPC. Model performance was evaluated using the concordance index (C-index), time-dependent receiver operating characteristic (ROC), decision curve analysis (DCA), and interpretability tools such as SHAP values and partial dependence plots (PDP).The 1-, 3-, and 5-year PFS rates were 100.0%, 91.5%, and 88.6% in the EBV = 0 group; 99.4%, 91.2%, and 88.5% in the > 0 and < 1500 group; and 92.3%, 81.0%, and 75.7% in the ≥ 1500 group, respectively, with statistically significant differences among the three groups (P = 0.0024). The RSF model outperformed other models with the highest C-index (0.778) and area under the ROC curve of 0.810 and 0.634 at 1 and 1.5 years, respectively. EBV DNA emerged as the most influential predictor across all interpretability analyses. Patients with EBV DNA ≥1500 copies/ml had the poorest predicted survival, showing a distinct threshold effect in the PDP.High EBV DNA levels were associated with poorer PFS in advanced NPC. Among the models evaluated, the RSF model demonstrated the best predictive performance and interpretability. EBV-informed AI modeling represents a promising approach for enhancing individualized risk prediction and clinical decision-making in NPC.