A pretreatment TNM-metabolic vulnerability score with EBV DNA adjustment for risk stratification in non-metastatic nasopharyngeal carcinoma

Background TNM stage and pretreatment plasma Epstein-Barr virus (EBV) DNA are central to risk assessment in nasopharyngeal carcinoma (NPC), but they do not fully capture host metabolic reserve. Methods We retrospectively analyzed 160 patients with non-metastatic NPC treated from 2013 to 2022. The integrated metabolic vulnerability score (IMVS; range, 0-3) assigned 1 point each for stage IVA, triglyceride-to-HDL cholesterol ratio <1.217, and body mass index <23.79 kg/m2. Cox regression and bootstrap internal validation evaluated progression-free survival (PFS), with EBV DNA included as an adjustment variable. A broader 271-patient cohort from the same institution was used only for internal sensitivity analysis. Results Thirty-three PFS events occurred in the modeling cohort. Five-year PFS was 100.0%, 91.9%, 72.1%, and 50.0% for IMVS scores 0, 1, 2, and 3, respectively. IMVS remained associated with PFS after adjustment for EBV DNA status (HR, 2.74; bootstrap percentile 95% CI, 1.89-4.75; P<0.001), although EBV DNA status itself was not independently significant in this cohort. The optimism-corrected AUC was 0.715 for stage IVA, THR, and BMI and 0.727 after adding EBV DNA. In the broader same-institution cohort, the association persisted but was attenuated (HR, 1.55; 95% CI, 1.14-2.10; P = 0.005). Conclusion IMVS is an exploratory, low-cost risk-stratification tool that may complement, rather than replace, TNM stage and plasma EBV DNA. Prospective external validation and recalibration of the data-derived thresholds are required before clinical use.