Extraoral Versus Intraoral Photobiomodulation for the Prevention of Oral Mucositis in Pediatric Patients Undergoing High‐Dose Methotrexate Chemotherapy

AIMS: To compare intraoral (IO) and extraoral (EO) photobiomodulation therapy (PBMT) for preventing oral mucositis (OM) in pediatric patients receiving high-dose methotrexate (HD-MTX). METHODS AND RESULTS: This prospective, open-label, randomized clinical trial included 75 HD-MTX treatment episodes from 31 pediatric patients aged 1-18 years. Each episode was randomized to IO-PBMT or EO-PBMT with red light at 660 nm. Preventive PBMT was initiated before HD-MTX infusion and administered daily until discharge. OM was assessed at baseline and on days 3, 5, and 10 using the World Health Organization scale. Pain, salivary pH, and salivary biochemical profiles were secondary or exploratory outcomes. Cumulative OM occurred in 22/37 IO-PBMT episodes (59.5%) and 12/38 EO-PBMT episodes (31.6%). After accounting for repeated episodes within patients, OM risk was higher with IO-PBMT (risk ratio, 1.84; 95% CI, 1.07-3.19; p = 0.029). Pain scores, salivary pH, and biochemical profiles did not differ significantly between groups. EO-PBMT required substantially less application time, and no adverse effects were reported. CONCLUSION: EO-PBMT was associated with lower cumulative OM occurrence, shorter application time, and good tolerability, supporting its use as a promising, less burdensome preventive strategy in pediatric oncology.