Limosilactobacillus reuteri for oral mucositis in patients undergoing radiotherapy for malignant head and neck tumors: a randomized controlled trial

Abstract Oral mucositis (OM) is a major toxicity in patients with head and neck cancer undergoing radiotherapy. Here we conducted a double-blind, placebo-controlled, randomized phase II trial (NCT06285591) from March 2024 to January 2025 at West China Hospital of Sichuan University to evaluate whether Limosilactobacillus reuteri ( L. reuteri ) supplementation could reduce severe OM (SOM; WHO Oral Toxicity criteria grade ≥3). A total of 160 patients were randomly assigned to receive L. reuteri probiotic lozenges or placebo twice daily during radiotherapy. The primary endpoint was the incidence of SOM, and secondary endpoints included SOM onset and duration, as well as the incidence, onset, and duration of any-grade OM. Safety outcomes were monitored throughout the study. The primary endpoint was met, with a lower incidence of SOM in the L. reuteri group than in the placebo group (37.5% vs 61.3%; relative risk 0.61; 95% confidence interval 0.44-0.85; absolute risk reduction 23.8 percentage points, 95% CI 8.7% to 38.8%; P = 0.004). L. reuteri supplementation also delayed SOM onset and shortened SOM duration. No significant safety concerns were observed. These findings indicate that L. reuteri supplementation reduces SOM incidence and severity in patients with head and neck cancer receiving radiotherapy.