Prognostic Value of Serum Transferrin Level before Radiotherapy on Radio-Sensitivity and Survival in Patients with Nasopharyngeal Carcinoma

**Background:** Nasopharyngeal carcinoma (NPC) has a high incidence in southern China, and intensity-modulated radiotherapy (IMRT) is the primary treatment. However, radio-sensitivity varies widely among patients, and existing predictors (e.g., EBV DNA, TNM stage) are insufficient. Serum transferrin (TRF), a widely available clinical nutrition and iron metabolism marker, has shown prognostic value in other cancers and may influence ferroptosis, an iron-dependent cell death mechanism implicated in radiation response. This study investigated whether pre-IMRT serum TRF levels predict radio-sensitivity and overall survival (OS) in NPC patients.

**Methods:** From October 2012 to October 2016, 348 NPC patients at the First Affiliated Hospital of Fujian Medical University were retrospectively analyzed. Serum TRF was measured by ELISA. Patients were divided into high (HTRF, >2.16 g/L, n=173) and low (LTRF, ≤2.16 g/L, n=175) groups based on the median. All received IMRT (GTVnx dose 66–76 Gy); 302 also received chemotherapy. Radio-sensitivity was defined as complete disappearance of local tumor on MRI and no residual tumor on electronic nasopharyngoscopy one month post-IMRT. Chi-square tests, logistic regression, Kaplan-Meier survival analysis, and Cox regression were used.

**Key Results:** The median serum TRF was 2.16 g/L (range 1.34–3.89). Overall, 242 patients (69.5%) were radio-sensitive and 106 (30.5%) were insensitive. The radio-sensitivity rate was significantly higher in the HTRF group (74.6%) than the LTRF group (64.6%) (χ²=4.103, p=0.043). Multivariable logistic regression confirmed TRF as an independent predictor of radio-sensitivity (OR=1.702; 95% CI 1.044–2.775; p=0.033). Median follow-up was 51.7 months. The 5-year OS was 78.4% overall, 84.4% in the HTRF group, and 73.1% in the LTRF group (log-rank χ²=5.388, p=0.02). Multivariable Cox regression showed low TRF was an independent prognostic factor for worse OS (HR=1.706; 95% CI 1.065–2.731; p=0.026). T stage and education level also significantly affected OS.

**Clinical Implications:** Low pre-IMRT serum TRF is a risk factor for radio-insensitivity and poor OS in NPC patients. TRF is a simple, inexpensive, and widely available test that could help identify patients at higher risk of treatment failure who may benefit from intensified or alternative therapeutic strategies. The findings align with the emerging role of ferroptosis in radiation response, as TRF is required for iron-dependent cell death. Limitations include the single-center retrospective design and lack of experimental mechanistic confirmation. Prospective multicenter studies and translational work on TRF/receptor/ferroptosis pathways are warranted.