Citrus Sinensis Peel Gel for Radiation-Induced Oral Mucositis

THE EFFECT OF CITRUS SINENSIS PEEL GEL ON RADIATION-INDUCED ORAL MUCOSITIS IN HEAD AND NECK CANCER PATIENTS (RANDOMIZED CONTROLLED TRIAL)

This randomized controlled clinical trial aims to evaluate the efficacy of Citrus sinensis peel extract gel in the treatment of radiation-induced oral mucositis in head and neck cancer patients. Thirty adult patients with head and neck cancer who develop oral mucositis during radiotherapy will be randomly allocated into two parallel groups. The intervention group will receive Citrus sinensis peel extract gel, while the control group will receive conventional supportive treatment. Clinical outcomes will be evaluated at baseline, 3 weeks, and 6 weeks, including pain intensity and severity of oral mucositis. Salivary total antioxidant capacity will be assessed at baseline and after 6 weeks.

Radiotherapy is an important treatment modality for head and neck cancer, but radiation-induced oral mucositis is a frequent complication that may cause significant pain and interfere with oral function and quality of life.

This randomized controlled, single-blinded clinical trial will evaluate the efficacy of Citrus sinensis peel extract gel in the treatment of radiation-induced oral mucositis in head and neck cancer patients.

A total of 30 eligible patients will be randomly allocated into two parallel groups of 15 participants each. The experimental group will receive Citrus sinensis peel extract gel containing 5% w/w ethanolic Citrus sinensis peel extract. The gel will be applied directly to the affected oral mucosa three times daily, preferably after meals and oral rinsing, for 6 weeks. Participants will be instructed to avoid eating or drinking for 30 minutes after application.

The control group will receive conventional supportive treatment consisting of miconazole oral gel, anti-inflammatory mouthwash, sodium bicarbonate mouthwash, BBC oral spray, Oracure gel, and systemic analgesics as needed.

Clinical evaluation will be performed at baseline, 3 weeks, and 6 weeks. Pain intensity will be assessed using a Visual Analogue Scale (VAS), and oral mucositis severity will be assessed using the World Health Organization (WHO) oral toxicity scale. The Arabic version of the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN) will also be used to assess symptom burden. Clinical photographs will be obtained at the assessment time points.

Unstimulated saliva will be collected at baseline and 6 weeks to assess total antioxidant capacity using a validated colorimetric assay.

The study will be conducted at the Department of Oral Medicine, Faculty of Dentistry, Alexandria University, with recruitment from the outpatient clinic of the Department of Clinical Oncology, Faculty of Medicine, Alexandria University.

Inclusion Criteria:

• Patients undergoing radiotherapy for head and neck cancer as postoperative (adjuvant) therapy or definitive therapy.
• Patients between 18-50 years.
• Both males and females.
• Patients whose radiotherapy treatment planned dose is 50 Gy or above 8
• Patients receiving radiotherapy alone or receiving concomitant cisplatin (or carboplatin) with radiotherapy.
• Patients who are clinically diagnosed with oral mucositis (WHO grade ≥1).

Exclusion Criteria:

• Smokers, due to impaired mucosal healing and increased inflammation
• Pregnant and lactating women
• Patients with poor oral hygiene
• Use of systemic or topical mucositis treatments within the past 7 days
• Patients allergic to orange
• Patients allergic to citrus peel or gel formulation components
• Patients with systemic diseases (e.g., hypertension, diabetes, cardic diseases etc.)
• Patients who have other oral lesions not related to mucositis (e.g., herpetic ulcers, candidiasis)