Intensity-modulated proton therapy versus volumetric-modulated ARC therapy in patients with nasopharyngeal carcinoma: A long-term, multicenter cohort study

Background: Data evaluating the impact of intensity-modulated proton therapy (IMPT) on survival among nasopharyngeal carcinoma (NPC) patients are limited. This study aims to elucidate the survival benefits and toxicity profiles of IMPT compared to modern photon therapy, volumetric-modulated arc therapy (VMAT), over an extended follow-up period. Methods: We analyzed data from NPC patients recorded in the Chang Gung Research Database. This analysis focused on individuals who received definitive radiotherapy, either IMPT or VMAT therapy, from 2016 to 2021. Patients with distant metastasis or concurrent other malignancies were excluded. We performed 1:1 matching based on stage, year of diagnosis, and age (± 10 years). Oncological outcomes and toxicities were assessed using Cox proportional hazards modeling. For sensitivity analysis, we employed inverse probability of treatment weighting and additional 1:2 matching. Results: Out of a 1,202 NPC patients’ cohort, 276 were selected from a subset of 294 who received IMPT and matched with an equivalent number of patients receiving VMAT. IMPT was associated with improved oncological outcomes after matching, with an adjusted hazard ratio (aHR) of 0.31 (95% CI: 0.15–0.62) for all-cause mortality and an aHR of 0.58 (95% CI: 0.34–0.99) for disease recurrence. Additionally, IMPT was linked to a reduced incidence of feeding tube placement, with an aHR of 0.31 (95% CI: 0.18–0.55). Competing risk and sensitivity analyses corroborated these trends, though the significance for disease recurrence was not consistent. Conclusion: IMPT was associated with significantly better overall survival outcomes and a lower incidence of dysphagia compared to VMAT in NPC patients. Further randomized trials are needed to confirm these findings.