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The purpose of this study was to examine the effectiveness of laser therapy in the prevention and/or healing of chemotherapy-induced oral mucositis lesions. This study also evaluated the ease and feasibility of the laser therapy and the impact of the treatment on improving the patient's quality of life.Fifteen patients with an episode of prior chemotherapy-induced grade 3 or 4 mucositis with 5-fluorouracil continuous infusion consented to participate in this study. All patients were provided with standardized mouth care instructions at the initiation of chemotherapy treatments. Enrolled patients received laser therapy treatments 24 hours before the chemotherapy and then recommenced weekly with evenly distributed exposure to the standardized designated areas by one operator during the entire cycle of chemotherapy at the same doses until the mucositis resolved or the chemotherapy cycle was completed. Intraoral perfusion was measured by laser Doppler technology. Patients were assessed for response to laser therapy according to standardized mucositis grading criteria by evaluating development of lesions, extent and duration of lesions, and time to healing. The effect of laser therapy on ability to continue planned chemotherapy, the reduction in dose, delays, and ability to maintain planned dose intensity were assessed. The impact of laser therapy on pain control was evaluated using the visual analogue score. A quality-of-life survey was completed by each patient at the initiation of chemotherapy and then weekly throughout the chemotherapy.Eleven of 15 patients experienced grade 0 mucositis, three patients experienced grade 1 to 2 mucositis, and one patient experienced grade 3 to 4 mucositis. Fourteen patients completed the laser therapy as planned, and none of the patients withdrew from the laser therapy treatments because of noncompliance. One patient continued to experience grade 4 mucositis that necessitated an interruption in the planned chemotherapy regimen and, consequently, the laser treatment. Patients tolerated the laser therapy very well and did not report any increased discomfort. No significant changes in perfusion were observed as a result of laser therapy.In this pilot study, laser therapy significantly reduced the incidence and the severity of mucositis in chemotherapy patients. The laser therapy does not appear to promote wound healing by affecting the intraoral perfusion, as assessed by Doppler measurements. The mechanisms involved in the mediating of the observed effects remain unknown at this time. Continued research is warranted to determine the optimal laser wavelength and parameters.