Oral mucositis is a common side effect of radiation therapy for head and neck cancer. Severe mucositis is followed by symptoms, such as extreme pain, mucosal ulceration and consequent limitations in swallowing and achieving adequate nutritional intake. Mucositis may also increase the risk of local and systemic infection and significantly affect quality of life and cost of care. Severe oral mucositis can lead to the need to interrupt or discontinue cancer therapy and thus may have an impact on cure of the primary disease. In spite of all the advances made in understanding the pathophysiology of oral mucositis, there is still no prophylactic therapy with proven efficacy and known risk factors. This review will discuss oral mucositis epidemiology, impact and side effects, pathogenesis, scoring scales and prevention.
If the inline PDF is not rendering correctly, you can download the PDF file here.
1. Global Burden of Disease Cancer Collaboration. Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability – adjusted life – years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2017;3:524.
2. Gatta G, Botta L, Sánchez MJ, Anderson LA, et al. Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 population-based study. Eur J Cancer. 2015;51:2130.
3. Didkowska J. Nowotwory złośliwe w Polsce w 2015 roku. Warszawa: Krajowy Rejestr Nowotworów; 2017.
4. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011;11:9-22.
5. Trotti A, Bellm LA, Epstein JB, et al. Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol. 2003;66(3):253-62.
6. Traynor AM, Richards GM, Hartig GK, et al. Comprehensive IMRT plus weekly cisplatin for advanced head and neck cancer: the University of Wisconsin experience. Head Neck. 2010;32(5):599-606.
7. Elting LS, Keefe DM, Sonis ST, et al. Burden of Illness Head and Neck Writing Committee. Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life. Cancer. 2008;113(10):2704-13.
8. Ang KK, Zhang Q, Rosenthal DI, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014;32(27):2940-50.
9. Epstein JB, Stewart KH. Radiation therapy and pain in patients with head and neck cancer. Eur J Cancer B Oral Oncol. 1993;29B:191-9.
10. Elting LS, Cooksley CD, Chambers MS, Garden AS. Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-andneck malignancies. Int J Radiat Oncol Biol Phys. 2007;68(4):1110-20.
11. Sonis S.T. Oral mucositis in head and neck cancer: Risk, biology, and management. Am Soc Clin Oncol Educ Book. 2013;33:e236
12. Sonis ST, Elting LS, Keefe D, et al. Perspectives on cancer therapy-induced mucosal injury. Cancer. 2004;100(9 Suppl):1995-2025.
13. Groome PA, O’Sullivan B, Mackillop WJ, et al. Compromised local control due to treatment interruptions and late treatment breaks in early glottic cancer: Population-based outcomes study supporting need for intensified treatment schedules. Int J Radiat Oncol Biol Phys. 2006;64:1002-12.
14. Robertson C, Robertson AG, Hendry JH, et al. Similar decreases in local tumor control are calculated for treatment protraction and for interruptions in the radiotherapy of carcinoma of the larynx in four centers. Int J Radiat Oncol Biol Phys. 1998;40:319-29.
15. Bese NS, Hendry J, Jeremic B. Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation. Int J Radiat Oncol Biol Phys. 2007;68:654-61.
16. Withers HR, Taylor JM, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol. 1988;27:131-46.
17. Maria OM, Eliopoulos N, Muanza T. Radiation induced oral mucositis. Front Oncol. 2017;7:89.
18. Eilers J, Million R. Prevention and management of oral mucositis in patients with cancer. Semin Oncol Nurs. 2007;23:201-12.
19. Chen SC, Lai YH, Huang BS, et al. Changes and predictors of radiation-induced oral mucositis in patients with oral cavity cancer during active treatment. Eur J Oncol Nurs. 2015;19(3):214-9.
20. Sonis ST. Pathobiology of oral mucositis: novel insights and opportunities. J Support Oncol. 2004; 5:3-11.
21. Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4:277-84.
22. WCCNR. Assessing stomatitis: refinement of the Western Consortium for Cancer Nursing Research (WCCNR) stomatitis staging system. Can Oncol Nurs J. 1998;4:160-5.
23. Etiz D, Orhan B, Demirüstü C, et al. Comparison of radiation-induced oral mucositis scoring systems. Tumori. 2002;88(5):379-84.
24. Riesenbeck D, Dorr W. Documentation of radiation-induced oral mucositis. Scoring systems. Strahlenther Onkol. 1998;174(Suppl 3):44-6.
25. Sonis ST, Eilers JP, Epstein JB, et al. Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Mucositis Study Group. Cancer. 1999;85(10):2103-13.
26. Dutsch-Wicherek M, Bańkowska-Woźniak M, Makarewicz A, et al. The evaluation of the intensity of radiation reaction using Dische scale in prediction of swallowing dysfunction and quality of life deterioration in patients with head and neck cancer treated with combined therapy including surgery, chemotherapy and radi. Medycyna Paliatywna w Praktyce. 2017;11(1):1-7.
27. McGuire DB, Peterson DE, Muller S, et al. The 20 item oral mucositis index: reliability and validity in bone marrow and stem cell transplant patients. Cancer Invest. 2002;20:893-903.
28. Trotti A, Byhardt R, Stetz J, et al. Common toxicity criteria: version 2.0. An improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys. 2000;47:13-47.
29. Sonis ST, Oster G, Fuchs F, et al. Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol. 2001;19:2201-5.
30. Al-Ansari S, Zecha JAEM, Barasch A, et al. Oral mucositis induced by anticancer therapies. Curr Oral Health Rep. 2015; 2:202-11.
31. Redding. Cancer therapy-related oral mucositis. J Dent Edu. 2005;69(8):919-29.
32. Köstler WJ, Hejna M, Wenzel C, Zielinski CC. Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment. CA Cancer J Clin. 2001;51(5):290-315.
33. Mahood DJ, Dose AM, Loprinzi CL, et al. Inhibition of fluorouracil-induced stomatitis by oral cryotherapy. J Clin Oncol. 1991;9:449-52.
34. Cascinu S, Fedeli A, Fedeli SL, Catalano G. Oral cooling (cryotherapy), an effective treatment for the prevention of 5-fluorouracil-induced stomatitis. Eur J Cancer B Oral Oncol. 1994;30B:234-6.
35. Watanabe S, Suemaru K, Nakanishi M, et al. Assessment of the hamster cheek pouch as a model for radiationinduced oral mucositis, and evaluation of the protective effects of keratinocyte growth factor using this model. Int J Radiat Biol. 2014;90(10):884-91.
36. Zheng C, Cotrim AP, Sunshine AN, et al. Prevention of radiation-induced oral mucositis after adenoviral vector-mediated transfer of the keratinocyte growth factor cDNA to mouse submandibular glands. Clin Cancer Res. 2009;15(14):4641-8.
37. Kanuga S. Cryotherapy and keratinocyte growth factor may be beneficial in preventing oral mucositis in patients with cancer, and sucralfate is effective in reducing its severity. J Am Dent Assoc. 2013;144(8):928-9.
38. Lalla RV, Sonis ST, Peterson DE. Management of oral mucositis in patients who have cancer. Dent Clin North Am. 2008;52(1):61-77.
39. Bardet E, Martin L, Calais G, et al. Subcutaneous compared with intravenous administration of amifostine in patients with head and neck cancer receiving radiotherapy: final results of the GORTEC2000-02 phase III randomized trial. J Clin Oncol. 2011;29(2):127-33.
40. Wasserman TH, Brizel DM, Henke M, et al. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and-neck cancer: 2-year follow-up of a prospective, randomized, phase III trial. Int J Radiat Oncol Biol Phys. 2005;63(4):985-90.
41. Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 2007;12(6):738-47.
42. Eisbruch A. Amifostine in the treatment of head and neck cancer: intravenous administration, subcutaneous administration, or none of the above. J Clin Oncol. 2011;29(2):119-21.
43. Gu J, Zhu S, Li X, et al. Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and metaanalysis based on randomized controlled trials. PLoS One. 2014;9(5):e95968.
44. Bensadoun RJ, Franquin JC, Ciais G, et al. Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer. Support Care Cancer. 1999;7(4):244-52.