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.