Introduction Radiation- and chemotherapy-induced mucositis cause pain, difficulty swallowing, and decreased oral intake. Fast Fact #121 explores the diagnosis and assessment of mucositis and Fast Fact #450 explores multi-modal treatment options. This Fast Fact focuses on prevention of radiation- (XRT) and chemotherapy-induced oral mucositis while broadly touching upon treatment options.

Risk factors The first step to preventing mucositis is to identify patients at risk of developing it. Patients undergoing radiation for head and neck cancer and/or patients undergoing cytotoxic chemotherapy regimens especially those containing fluorouracil, methotrexate, or etoposide seem to be at particular risk for mucositis. Additionally, patients who smoke, have poor hygiene, poor nutritional status, and age greater than 65 may be at greater risk for severe symptoms.

Prevention There are many prevention schemas to consider for patients at risk of developing mucositis, but unfortunately, there is no gold standard protocol. A systematic review of suggested that no intervention is proven to prevent or treat mucositis on its own. Instead, individualized, multi-modal strategies are recommended.

• Oral care: At least two weeks prior to the start of radiation to the head and neck region, or the use of chemotherapy that is expected to cause severe and prolonged neutropenia (e.g., for acute leukemia), patients should undergo a thorough oral/dental exam with appropriate dental extraction and repair or removal of dental prostheses. Patients should be educated on maintaining good oral hygiene including daily brushing with a soft bristle toothbrush, flossing, use of fluoride plaques, and avoiding denture use. Mouth rinses that contain chlorhexidine or a mixture of baking soda, salt, and water can prevent the build-up of bacterial overgrowth and remove dead cells. Patients should avoid caustic and drying foods such as: sharp potato chips, alcoholic beverages, mouth rinses with alcohol, hot beverages, and acidic foods.
• Over-the-counter supplements: Ice chip therapy (patient holds ice chips in their mouth 30 minutes prior to an infusion of a cytotoxic chemotherapy) may reduce the incidence of severe chemotherapy-induced mucositis. For radiation-induced mucositis in head and neck cancers, povidone iodine rinses; honey swish and spits administered before each radiation dose, daily zinc supplementation, and 5-15 grams of oral glutamine 2-3 times a day may help prevent mucositis.
• Radiation therapy technique: Advanced radiotherapy techniques such as 3D-conformal therapy and intensity modulated therapy decrease radiation toxicity by limiting doses to the normal oral mucosa. Other XRT modifications that decrease toxicity include using shields over normal tissues, decreasing the radiation fraction size, and decreasing overall treatment time. Severe mucositis may require a 5-to-7-day radiation treatment break to allow for tissue recovery. However, a prolonged break is associated with inferior local control rates and survival.
• Prophylactic feeding tube placement: for patients with severe pain brought on by oral intake, gastric feeding tube placement may be considered to prevent mucositis pain. See Fast Fact #318.

Treatment of mucositis: This is covered in more detail in Fast Fact #450, particularly the role of opioids (topical and systemic) and other systemic non-opioid analgesics.

• Treatment of infection: Prophylactic use of antifungal, antibacterial or antiviral medications does not decrease the incidence of mucositis. However, clinicians should consider potential super-infection, and have a low threshold to obtain cultures, especially for fungal and viral infections. Of note, viral infections such as herpes may not present with classic physical examination findings.
• Local anesthetics and topical agents: Liquid lidocaine and diphenhydramine are routinely used to relieve pain. Several topical agents are available in commercial and non-commercial preparations: e.g., Gelcair, topical lidocaine, Maalox, diphenhydramine, and nystatin, etc. Most local anesthetics do not provide mucosal protection nor hasten recovery, in fact many are associated with altered taste and oral intake. However, benzydamine is a mouth rinse with analgesic, anesthetic, anti-inflammatory, and antimicrobial properties and has been shown in randomized controlled trials to reduce ulcer rate and incidence as well as reduce need for opioids. Some patients find the addition of a Carafate slurry, a liquid antacid, or topical honey provides temporary analgesia.
• Low-energy laser therapy: Some studies have shown pain relief with the use of low power laser therapy delivered in a fractionated course three times a week. Its mechanism of action is thought to be due to anti-inflammatory effects of the laser irradiation on local tissue; however, its use remains experimental, and data has been mixed with regards to wound healing.

References

1. Berger AM, Kilroy TJ. Oral Complications. In: DeVita V, et al, eds. Cancer: Principles and Practices of Oncology. 6th Edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2001.
2. Rodriguez-Caballero A, Torres-Lagares D, et al. Cancer treatment-induced oral mucositis: a critical review. Int J Oral Maxillofac Surg 2012; 41: 225-38.
3. Epstein JB, Silverman Jr S, et al. Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter randomized, double-blind, placebo-controlled clinical trial. Cancer 2001; 92: 875-80.
4. Bensinger W, Schubert M, Ang KK, et al. NCCN Task Force Report: Prevention and management of mucositis in cancer care. J Natl Compr Canc Netw 2008; 6:s1-s21.
5. Xu JL, Xia R, Sun ZH, et al. Effect of honey use on the management of radio-chemotherapy-induced mucositis: a meta-analysis of randomized controlled trials. Int J Oral Maxillofac Surg 2016; 45:1618-1625.
6. Lin YS, Lin LC, Lin SW, et al. Discrepancy of the effects of zinc supplementation on the prevention of radiotherapy-induced mucositis between patients with nasopharyngeal carcinoma and those with oral cancers: subgroup analysis of a double-blind, randomized study. Nutr Cancer 2010; 62:682-691.
7. Alsubaie HM, Alsini AY, Alsubaie KM, et al. Glutamine for prevention and alleviation of radiation-induced oral mucositis in patients with head and neck squamous cell cancer: Systematic review and meta-analysis of controlled trials. Head Neck. 2021;43(10):3199-3213.
8. Brown TJ, Gupta A. Management of cancer therapy-associated oral mucositis. JCO Oncology Practice March 2020; 16(3): https://doi.org/10.1200/JOP.19.00652
9. Khanal B, Baliga M, Uppal N. Effect of topical honey on limitation of radiation-induced oral mucositis: an interventional study. Int J Oral Maxillofac Surg 2010; 39:1181-90.
10. Migliorati C, Hewson I, et al. Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Center 2013; 21:333-341.

Version History: This Fast Fact was originally edited by David E Weissman MD and published in January 2005. 2nd Edition in April 2009; 3rd Edition in July 2015; 4th Edition in April 2024.
Conflicts of Interest: None to report.