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Oral Mucositis

  • Timothy B. Winslow
  • Brian Niedzwecki
  • Anurag K. SinghEmail author
Chapter

Abstract

Mucositis is defined as damage to the mucosa of the alimentary tract occurring as a result of chemotherapy and/or radiation therapy. Oral mucositis refers to mucosal damage restricted to the oral cavity and oropharynx. Oral mucositis often occurs with concurrent chemoradiation in the treatment of head and neck cancers. Patients report oral mucositis as the single most troublesome acute side effect of radiation therapy (RT) to the head and neck [1]. Similarly, some patients report their oral symptoms as the worst side effect of their chemotherapy [2]. Typically, oral mucositis is very painful. This pain impairs nutritional intake and quality of life and often requires opioid analgesics [3, 4]. Complications of oral mucositis cause patients to need hospitalization or breaks in treatment in up to 11 % of cases [5, 6]. Severe mucositis can almost double the supportive care costs of patients [7].

References

  1. 1.
    Rose-Ped AM, Bellm LA, Epstein JB, et al. Complications of radiation therapy for head and neck cancers. The patient’s perspective. Cancer Nurs. 2002;25:461–7. quiz 468-9CrossRefPubMedGoogle Scholar
  2. 2.
    Dibble SL, Shiba G, MacPhail L, et al. MacDibbs mouth assessment. A new tool to evaluate mucositis in the radiation therapy patient. Cancer Pract. 1996;4:135–40.PubMedGoogle Scholar
  3. 3.
    Lalla RV, Bowen J, Barasch A, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120:1453–61.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4:277–84.CrossRefPubMedGoogle Scholar
  5. 5.
    Jones JA, Avritscher EB, Cooksley CD, et al. Epidemiology of treatment-associated mucosal injury after treatment with newer regimens for lymphoma, breast, lung, or colorectal cancer. Support Care Cancer. 2006;14:505–15.CrossRefPubMedGoogle Scholar
  6. 6.
    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;66:253–62.CrossRefPubMedGoogle Scholar
  7. 7.
    Nonzee NJ, Dandade NA, Markossian T, et al. Evaluating the supportive care costs of severe radiochemotherapy-induced mucositis and pharyngitis. Cancer. 2008;113:1446–52.CrossRefPubMedGoogle Scholar
  8. 8.
    Vera-Llonch M, Oster G, Hagiwara M, et al. Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma. Cancer. 2006;106:329–36.CrossRefPubMedGoogle Scholar
  9. 9.
    Sonis ST. New thoughts on the initiation of mucositis. Oral Dis. 2010;16:597–600.CrossRefPubMedGoogle Scholar
  10. 10.
    Logan RM, Stringer AM, Bowen JM, et al. The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. Cancer Treat Rev. 2007;33:448–60.CrossRefPubMedGoogle Scholar
  11. 11.
    WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization; 1979. p. 1–46.Google Scholar
  12. 12.
    Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol*Biol*Physics. 1995;31:1341–6.CrossRefGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    Van der Schueren E, Van den Bogaert W, Vanuytsel L, et al. Radiotherapy by multiple fractions per day (MFD) in head and neck cancer: acute reactions of skin and mucosa. Int J Radiat Oncol Biol Phys. 1990;19:301–11.CrossRefPubMedGoogle Scholar
  15. 15.
    Byfield JE, Frankel SS, Sharp TR, et al. Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation. Int J Radiat Oncol Biol Phys. 1985;11:791–800.CrossRefPubMedGoogle Scholar
  16. 16.
    Seto BG, Kim M, Wolinsky L, et al. Oral mucositis in patients undergoing bone marrow transplantation. Oral Surg Oral Med Oral Pathol. 1985;60:493–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Eilers J, Berger AM, Petersen MC. Development, testing, and application of the oral assessment guide. Oncol Nurs Forum. 1988;15:325–30.PubMedGoogle Scholar
  18. 18.
    Spijkervet FK, van Saene HK, Panders AK, et al. Scoring irradiation mucositis in head and neck cancer patients. J Oral Pathol Med. 1989;18:167–71.CrossRefPubMedGoogle Scholar
  19. 19.
    Maciejewski B, Skladowski K, Pilecki B, et al. Randomized clinical trial on accelerated 7 days per week fractionation in radiotherapy for head and neck cancer. Preliminary report on acute toxicity. Radiother Oncol. 1996;40:137–45.CrossRefPubMedGoogle Scholar
  20. 20.
    Hickey AJ, Toth BB, Lindquist SB. Effect of intravenous hyperalimentation and oral care on the development of oral stomatitis during cancer chemotherapy. J Prosthet Dent. 1982;47:188–93.CrossRefPubMedGoogle Scholar
  21. 21.
    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 Stud Group Cancer. 1999;85:2103–13.Google Scholar
  22. 22.
    Sung L, Tomlinson GA, Greenberg ML, et al. Validation of the oral mucositis assessment scale in pediatric cancer. Pediatr Blood Cancer. 2007;49:149–53.CrossRefPubMedGoogle Scholar
  23. 23.
    Kumar PSS, Balan A, Sankar A, et al. Radiation induced oral mucositis. Indian J Palliat Care. 2009;15:95–102.Google Scholar
  24. 24.
    Dodd MJ, Facione NC, Dibble SL, et al. Comparison of methods to determine the prevalence and nature of oral mucositis. Cancer Pract. 1996;4:312–8.PubMedGoogle Scholar
  25. 25.
    Rosenthal DI, Trotti A. Strategies for managing radiation-induced mucositis in head and neck cancer. Semin Radiat Oncol. 2009;19:29–34.CrossRefPubMedGoogle Scholar
  26. 26.
    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(Suppl 1):S1–21. quiz S22-4PubMedGoogle Scholar
  27. 27.
    Carnel SB, Blakeslee DB, Oswald SG, et al. Treatment of radiation- and chemotherapy-induced stomatitis. Otolaryngol Head Neck Surg. 1990;102:326–30.CrossRefPubMedGoogle Scholar
  28. 28.
    Coda BA, O’Sullivan B, Donaldson G, et al. Comparative efficacy of patient-controlled administration of morphine, hydromorphone, or sufentanil for the treatment of oral mucositis pain following bone marrow transplantation. Pain. 1997;72:333–46.CrossRefPubMedGoogle Scholar
  29. 29.
    Lalla RV, Sonis ST, Peterson DE. Management of oral mucositis in patients with cancer. Dent Clin N Am. 2008;52:61–viii.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Nguyen HM, Reyland ME, Barlow LA. Mechanisms of taste bud cell loss after head and neck irradiation. J Neurosci. 2012;32:3474–84.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    National Cancer Institute, (editor). Radiation therapy and you: support for people with cancer. Bethesda: US Department of Health and Human Services; 2007.Google Scholar
  32. 32.
    Capuano G, Grosso A, Gentile PC, et al. Influence of weight loss on outcomes in patients with head and neck cancer undergoing concomitant chemoradiotherapy. Head Neck. 2008;30:503–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Muller-Peddinghaus R, Wurl M, Lenoir G, et al. The effect of benzydamine on the generation and interaction of reactive oxygen species and cyclo- and lipoxygenase. Arzneimittelforschung. 1987;37:601–5.PubMedGoogle Scholar
  34. 34.
    Sein Anand J, Lukasik – Glębocka M, Paweł Korolkiewicz R. Letter to the Editor: “Recreational abuse with benzydamine hydrochloride (tantum rosa)”. Clin Toxicol. 2007;45:198–9.CrossRefGoogle Scholar
  35. 35.
    Rubenstein EB, Peterson DE, Schubert M, et al. Clinical practice guidelines for the prevention and treatment of cancer therapy–induced oral and gastrointestinal mucositis. Cancer. 2004;100:2026–46.CrossRefPubMedGoogle Scholar
  36. 36.
    Epstein JB, Silverman Jr S, Paggiarino DA, et al. Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer. 2001;92:875–85.CrossRefPubMedGoogle Scholar
  37. 37.
    McGuire DB, Correa ME, Johnson J, et al. The role of basic oral care and good clinical practice principles in the management of oral mucositis. Support Care Cancer. 2006;14:541–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Schubert MM, Eduardo FP, Guthrie KA, et al. A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation. Support Care Cancer. 2007;15:1145–54.CrossRefPubMedGoogle Scholar
  39. 39.
    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;7:244–52.CrossRefPubMedGoogle Scholar
  40. 40.
    Migliorati C, Hewson I, Lalla R, et al. Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:333–41.CrossRefPubMedGoogle Scholar
  41. 41.
    Saunders D, Epstein J, Elad S, et al. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:3191–207.CrossRefPubMedGoogle Scholar
  42. 42.
    Leenstra JL, Miller RC, Qin R, et al. Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy: a phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]). J Clin Oncol. 2014;32:1571–7.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Sudoh Y, Cahoon EE, Gerner P, et al. Tricyclic antidepressants as long-acting local anesthetics. Pain. 2003;103:49–55.CrossRefPubMedGoogle Scholar
  44. 44.
    Epstein JB, Truelove EL, Oien H, et al. Oral topical doxepin rinse: analgesic effect in patients with oral mucosal pain due to cancer or cancer therapy. Oral Oncol. 2001;37:632–7.CrossRefPubMedGoogle Scholar
  45. 45.
    Epstein JB, Epstein JD, Epstein MS, et al. Doxepin rinse for management of mucositis pain in patients with cancer: one week follow-up of topical therapy. Spec Care Dentist. 2008;28:73–7.CrossRefPubMedGoogle Scholar
  46. 46.
    Lin LC, Que J, Lin LK, et al. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomized study. Int J Radiat Oncol Biol Phys. 2006;65:745–50.CrossRefPubMedGoogle Scholar
  47. 47.
    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;62:682–91.CrossRefPubMedGoogle Scholar
  48. 48.
    Maitra AK, Dorani B. Role of zinc in post-injury wound healing. Arch Emerg Med. 1992;9:122–4.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    El-Sayed S, Nabid A, Shelley W, et al. Prophylaxis of radiation-associated mucositis in conventionally treated patients with head and neck cancer: a double-blind, phase III, randomized, controlled trial evaluating the clinical efficacy of an antimicrobial lozenge using a validated mucositis scoring system. J Clin Oncol. 2002;20:3956–63.CrossRefPubMedGoogle Scholar
  50. 50.
    Giles FJ, Miller CB, Hurd DD, et al. A phase III, randomized, double-blind, placebo-controlled, multinational trial of iseganan for the prevention of oral mucositis in patients receiving stomatotoxic chemotherapy (PROMPT-CT trial). Leuk Lymphoma. 2003;44:1165–72.CrossRefPubMedGoogle Scholar
  51. 51.
    Trotti A, Garden A, Warde P, et al. A multinational, randomized phase III trial of iseganan HCl oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for head-and-neck malignancy. Int J Radiat Oncol Biol Phys. 2004;58:674–81.CrossRefPubMedGoogle Scholar
  52. 52.
    Carter DL, Hebert ME, Smink K, et al. Double blind randomized trial of sucralfate vs placebo during radical radiotherapy for head and neck cancers. Head Neck. 1999;21:760–6.CrossRefPubMedGoogle Scholar
  53. 53.
    McGuire DB, Fulton JS, Park J, et al. Systematic review of basic oral care for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:3165–77.CrossRefPubMedGoogle Scholar
  54. 54.
    Lalla RV, Gordon GB, Schubert M, et al. A randomized, double-blind, placebo-controlled trial of misoprostol for oral mucositis secondary to high-dose chemotherapy. Support Care Cancer. 2012;20:1797–804.CrossRefPubMedGoogle Scholar
  55. 55.
    Duenas-Gonzalez A, Sobrevilla-Calvo P, Frias-Mendivil M, et al. Misoprostol prophylaxis for high-dose chemotherapy-induced mucositis: a randomized double-blind study. Bone Marrow Transplant. 1996;17:809–12.PubMedGoogle Scholar
  56. 56.
    Veness MJ, Foroudi F, Gebski V, et al. Use of topical misoprostol to reduce radiation-induced mucositis: results of a randomized, double-blind, placebo-controlled trial. Australas Radiol. 2006;50:468–74.CrossRefPubMedGoogle Scholar
  57. 57.
    Fox PC, Atkinson JC, Macynski AA, et al. PIlocarpine treatment of salivary gland hypofunction and dry mouth (xerostomia). Arch Intern Med. 1991;151:1149–52.CrossRefPubMedGoogle Scholar
  58. 58.
    Jensen SB, Jarvis V, Zadik Y, et al. Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:3223–32.CrossRefPubMedGoogle Scholar
  59. 59.
    Scarantino C, LeVeque F, Swann RS, et al. Effect of pilocarpine during radiation therapy: results of RTOG 97-09, a phase III randomized study in head and neck cancer patients. J Support Oncol. 2006;4:252–8.PubMedGoogle Scholar
  60. 60.
    Warde P, O’Sullivan B, Aslanidis J, et al. A phase III placebo-controlled trial of oral pilocarpine in patients undergoing radiotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2002;54:9–13.CrossRefPubMedGoogle Scholar
  61. 61.
    Lockhart PB, Brennan MT, Kent ML, et al. Randomized controlled trial of pilocarpine hydrochloride for the moderation of oral mucositis during autologous blood stem cell transplantation. Bone Marrow Transplant. 2005;35:713–20.CrossRefPubMedGoogle Scholar
  62. 62.
    Allison RR, Ambrad AA, Arshoun Y, et al. Multi-institutional, randomized, double-blind, placebo-controlled trial to assess the efficacy of a mucoadhesive hydrogel (MuGard) in mitigating oral mucositis symptoms in patients being treated with chemoradiation therapy for cancers of the head and neck. Cancer. 2014;120:1433–40.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Pettit L, Sanghera P, Glaholm J, et al. The use of MuGard™, Caphosol® and Episil® in patients undergoing chemoradiotherapy for squamous cell carcinoma of the head and neck. J Radiother Pract. 2014;13:218–25.CrossRefGoogle Scholar
  64. 64.
    Vera-Llonch M, Oster G, Ford CM, et al. Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies. Support Care Cancer. 2007;15:491–6.CrossRefPubMedGoogle Scholar
  65. 65.
    Vera-Llonch M, Oster G, Ford CM, et al. Oral mucositis and outcomes of autologous hematopoietic stem-cell transplantation following high-dose melphalan conditioning for multiple myeloma. J Support Oncol. 2007;5:231–5.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Timothy B. Winslow
    • 1
  • Brian Niedzwecki
    • 1
  • Anurag K. Singh
    • 2
    Email author
  1. 1.Department of Head and Neck Plastic and Reconstructive SurgeryRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Radiation Medicine DepartmentRoswell Park Cancer InstituteBuffaloUSA

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