Comparable efficacy of extraoral and intraoral photobiomodulation in preventing oral mucositis during high-dose methotrexate therapy in pediatric oncology: A single-blind randomized controlled trial

Purpose: This prospective randomized controlled clinical study compared intraoral (IO) and extraoral (EO) photobiomodulation (PBM) for the prevention of chemotherapy-induced oral mucositis (OM) in pediatric oncology patients. Methods: A total of 155 patients (1–18 years), receiving high-dose methotrexate (HDMTX) for leukemia, lymphoma, or osteosarcoma, were randomized to PBM-IO (n = 73) or PBM-EO (n = 82). Preventive PBM was administered daily from hospital admission through discharge. Both protocols used red light with equivalent dosimetry (660 nm, 100 mW, 1 J per point). PBM-EO required 30 s/session, whereas PBM-IO required approximately 6 min, excluding patient handling time. OM occurrence, severity (WHO scale), plaque index, and pain (numeric rating scale) were assessed on days 0, 3, 5, and 10 after HDMTX infusion. Results: The overall OM occurrence was 35.5%, with no significant difference between PBM-IO (41.1%) and PBM-EO (30.5%) groups (p = 0.168). No statistically significant differences were observed between groups for OM severity, pain, salivary pH, or plaque index at any time point (p > 0.05). Multivariable ordinal logistic regression demonstrated that PBM modality was not independently associated with OM severity. As expected, increasing age (OR = 1.14; 95% CI: 1.04–1.25; p = 0.004) and higher HDMTX dose (OR = 1.24; 95% CI: 1.03–1.49; p = 0.021) were significantly associated with greater OM severity. Median pain scores remained 0 at all assessment points in both groups. Conclusion: Extraoral PBM demonstrated comparable effectiveness to intraoral for OM prevention in pediatric patients undergoing HDMTX chemotherapy, while reducing application time. © The Author(s) 2026.