Outcomes of Supplementation With β-Hydroxy-β-methylbutyrate, Arginine, and Glutamine During Carbon-ion Radiotherapy for Head and Neck Cancer: A Prospective Exploratory Study

BACKGROUND/AIM: Acute mucositis and dermatitis frequently occur during radiotherapy for head and neck malignancies and can impair oral intake and quality of life (QOL). Nutritional supplementation using β-hydroxy-β-methylbutyrate (HMB), arginine (Arg), and glutamine (Gln) may support tissue repair and protein metabolism. This prospective single-arm exploratory study evaluated the feasibility of continuous oral HMB-Arg-Gln supplementation during carbon-ion radiotherapy (CIRT). PATIENTS AND METHODS: Sixteen consecutive patients with head and neck tumors who underwent CIRT were enrolled. Patients received oral HMB-Arg-Gln supplementation twice daily from the start of CIRT until 2 weeks after treatment completion. The primary endpoint was feasibility, defined as completion of CIRT with continuous supplementation without grade ≥4 acute toxicity or the need for enteral or parenteral nutritional support. Acute mucositis and radiation dermatitis were graded weekly using Common Terminology Criteria for Adverse Events v4.03 and Radiation Therapy Oncology Group criteria. Health-related QOL was assessed using Short Form-8 (SF-8) questionnaires before CIRT, at completion of 16 fractions, and 2 months after treatment. RESULTS: All patients completed the CIRT course with supplementation, meeting the predefined feasibility criteria. No grade ≥4 acute toxicities occurred. Temporal mucositis and dermatitis patterns were consistent with those typically reported during radiotherapy, with peak severity near the end of treatment. SF-8 physical component summary scores had decreased at CIRT completion but had partially recovered by 2 months, whereas mental component summary scores remained relatively stable. CONCLUSION: Continuous oral HMB-Arg-Gln supplementation during CIRT for head and neck tumors was feasible and well tolerated. Treatment was completed without severe acute toxicity, and QOL was largely maintained during and after therapy. Nutritional supplementation may support patients undergoing particle therapy.