Ozonated water mouthrinse for radiation-induced oral mucositis in non-keratinizing nasopharyngeal carcinoma: a retrospective cohort study

PURPOSE: To evaluate the association between documented ozonated water (OW) mouthrinsing and radiotherapy-induced oral mucositis (OM) outcomes in patients with nasopharyngeal carcinoma (NPC). METHODS: A single-center retrospective cohort study included 65 NPC patients receiving definitive chemoradiotherapy. Among them, 34 had documented OW mouthrinsing during radiotherapy and 31 served as controls without documented OW use. The primary endpoint was time to first WHO grade ≥ 2 OM. Because OW initiation was time-varying, time-dependent Cox and landmark analyses were used as the main time-aware approaches, with propensity score-based models retained as supportive association analyses. Secondary outcomes included the incidence of grade ≥ 2 OM at fractions 15 and 30, peak oral pain scores, and post-EoRT mucosal healing interval. RESULTS: OW initiation occurred at a median fraction of 2.5 (IQR 1-4.75; range F1-F22). In time-aware analyses, documented OW exposure was associated with a lower hazard of first grade ≥ 2 OM in both the time-dependent Cox model (HR 0.35, 95% CI 0.20-0.63; P < 0.001) and the 10-fraction landmark analysis (HR 0.47, 95% CI 0.26-0.83; P = 0.010). Supportive fixed ever-use propensity score-based analyses were directionally consistent, including the stabilized IPTW model (HR 0.48, 95% CI 0.27-0.88; P = 0.018). At fraction 30, 50.0% of OW patients versus 90.3% of controls had grade ≥ 2 OM. The OW group also reported lower peak oral pain (P < 0.01) and a nonsignificant trend toward a shorter post-EoRT mucosal healing interval. CONCLUSION: Documented OW mouthrinsing during radiotherapy was associated with lower OM burden and reduced oral pain in this retrospective NPC cohort. Given the observational design, time-varying exposure, residual confounding, and chart-based exposure and outcome ascertainment, these findings should be interpreted as exploratory associations requiring prospective validation.