Skip to main content

Advertisement

SpringerLink
Log in

Pathogenesis and Amelioration of Radiation-Induced Oral Mucositis

  • Head and Neck Cancer (PL Swiecicki, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Oral mucositis (OM) causes significant detriment to patient quality of life. Despite advances in RT, chemotherapy, and surgery for HNC which have led to improved local control and survival, management of certain toxicities such as OM have not kept pace. Numerous strategies have emerged with demonstrable benefit in preventing severe OM. However, ones which are not only effective, but practical and affordable to implement are rare. For example, infusion of growth factors or free radical scavengers, and daily treatment of intra-oral sites with lasers are supported by high-quality evidence but have not become widely adopted. It falls to familiarity of the physician with the available preventative measures and ultimately, patient preference in accepting which strategies for OM amelioration are used. In this review, we present a pathophysiological-based review of prevention techniques available for reducing the incidence and duration of severe OM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7–33.

    Article  PubMed  Google Scholar 

  2. Raber-Durlacher JE, Elad S, Barasch A. Oral mucositis. Oral Oncol. 2010;46:452–6.

    Article  PubMed  Google Scholar 

  3. Cinausero M, Aprile G, Ermacora P, Basile D, Vitale MG, Fanotto V, et al. New frontiers in the pathobiology and treatment of cancer regimen-related mucosal injury. Front Pharmacol. 2017;8:354.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Shaikh T, Handorf EA, Murphy CT, Mehra R, Ridge JA, Galloway TJ. The impact of radiation treatment time on survival in patients with head and neck cancer. Int J Radiat Oncol Biol Phys. 2016;96:967–75.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Elting LS, Cooksley CD, Chambers MS, Garden AS. Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies. Int J Radiat Oncol Biol Phys. 2007;68:1110–20.

    Article  PubMed  Google Scholar 

  6. Nonzee NJ, Dandade NA, Patel U, Markossian T, Agulnik M, Argiris A, et al. Evaluating the supportive care costs of severe radiochemotherapy-induced mucositis and pharyngitis : results from a Northwestern University Costs of Cancer Program pilot study with head and neck and nonsmall cell lung cancer patients who received care at a county hospital, a Veterans Administration hospital, or a comprehensive cancer care center. Cancer. 2008;113:1446–52.

    Article  PubMed  Google Scholar 

  7. Al-Dasooqi N, Sonis ST, Bowen JM, Bateman E, Blijlevens N, Gibson RJ, et al. Emerging evidence on the pathobiology of mucositis. Support Care Cancer. 2013;21:3233–41.

    Article  PubMed  Google Scholar 

  8. Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4:277–84.

    Article  CAS  PubMed  Google Scholar 

  9. Borrego-Soto G, Ortiz-Lopez R, Rojas-Martinez A. Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer. Genet Mol Biol. 2015;38:420–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Georgiou M, Patapatiou G, Domoxoudis S, Pistevou-Gompaki K. Oral Mucositis: understanding the pathology and management. Hippokratia. 2012;16:215–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24:981–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Harris DJ, Eilers J, Harriman A, Cashavelly BJ, Maxwell C. Putting evidence into practice (R): evidence-based interventions for the management of oral mucostis. Clin J Oncol Nurs. 2008;12:141–52.

    Article  PubMed  Google Scholar 

  13. Salmon TB, Evert BA, Song BW, Doetsch PW. Biological consequences of oxidative stress-induced DNA damage in Saccharomyces cerevisiae. Nucleic Acids Res. 2004;32:3712–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sonis ST, Scherer J, Phelan S, Lucey CA, Barron JE, O’Donnell KE, et al. The gene expression sequence of radiated mucosa in an animal mucositis model. Cell Prolif. 2002;35(Suppl 1):93–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sonis ST, Peterson RL, Edwards LJ, Lucey CA, Wang L, Mason L, et al. Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters. Oral Oncol. 2000;36:373–81.

    Article  CAS  PubMed  Google Scholar 

  16. Maria OM, Eliopoulos N, Muanza T. Radiation-induced oral mucositis. Front Oncol. 2017;7:89.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lima V, Brito GA, Cunha FQ, Reboucas CG, Falcao BA, Augusto RF, et al. Effects of the tumour necrosis factor-alpha inhibitors pentoxifylline and thalidomide in short-term experimental oral mucositis in hamsters. Eur J Oral Sci. 2005;113:210–7.

    Article  CAS  PubMed  Google Scholar 

  18. de Koning BA, van Dieren JM, Lindenbergh-Kortleve DJ, van der Sluis M, Matsumoto T, Yamaguchi K, et al. Contributions of mucosal immune cells to methotrexate-induced mucositis. Int Immunol. 2006;18:941–9.

    Article  PubMed  Google Scholar 

  19. Al-Dasooqi N, Gibson RJ, Bowen JM, Logan RM, Stringer AM, Keefe DM. Matrix metalloproteinases are possible mediators for the development of alimentary tract mucositis in the dark agouti rat. Exp Biol Med (Maywood). 2010;235:1244–56.

    Article  CAS  PubMed  Google Scholar 

  20. Wang ZH, Zhang SZ, Zhang ZY, Zhang CP, Hu HS, Tu WY, et al. Protecting the oral mucosa in patients with oral tongue squamous cell carcinoma treated postoperatively with intensity-modulated radiotherapy: a randomized study. Laryngoscope. 2012;122:291–8.

    Article  PubMed  Google Scholar 

  21. Grant SR, Williamson TD, Stieb S, Shah SJ, David Fuller C, Rosenthal DI, et al. A Dosimetric comparison of oral cavity sparing in the unilateral treatment of early stage tonsil cancer: IMRT, IMPT, and tongue-deviating oral stents. Adv Radiat Oncol. 2020;5:1359–63.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Manur JG, Vidyasagar N. Correlation of planning target volume with mucositis for head-and-neck cancer patients undergoing chemoradiation. J Cancer Res Ther. 2020;16:565–8.

    Article  CAS  PubMed  Google Scholar 

  23. Chao KS, Majhail N, Huang CJ, Simpson JR, Perez CA, Haughey B, et al. Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: a comparison with conventional techniques. Radiother Oncol. 2001;61:275–80.

    Article  CAS  PubMed  Google Scholar 

  24. Peng G, Wang T, Yang KY, Zhang S, Zhang T, Li Q, et al. A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma. Radiother Oncol. 2012;104:286–93.

    Article  PubMed  Google Scholar 

  25. Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA, Clark C, et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2011;12:127–36.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Al-Mamgani A, van Rooij P, Verduijn GM, Mehilal R, Kerrebijn JD, Levendag PC. The impact of treatment modality and radiation technique on outcomes and toxicity of patients with locally advanced oropharyngeal cancer. Laryngoscope. 2013;123:386–93.

    Article  PubMed  Google Scholar 

  27. Dean JA, Welsh LC, Wong KH, Aleksic A, Dunne E, Islam MR, et al. Normal tissue complication probability (ntcp) modelling of severe acute mucositis using a novel oral mucosal surface organ at risk. Clin Oncol-Uk. 2017;29:263–73.

    Article  CAS  Google Scholar 

  28. Brodin NP, Kabarriti R, Garg MK, Guha C, Tome WA. Systematic review of normal tissue complication models relevant to standard fractionation radiation therapy of the head and neck region published after the QUANTEC reports. Int J Radiat Oncol Biol Phys. 2018;100:391–407.

    Article  PubMed  Google Scholar 

  29. • Chera BS, Amdur RJ, Tepper JE, Tan X, Weiss J, Grilley-Olson JE, et al. Mature results of a prospective study of deintensified chemoradiotherapy for low-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma. Cancer. 2018;124:2347–54 Therapeutic de-intensification is an area of major interest in oropharynx malignancies. Clinicians should be aware of its appropriateness for select patients and how it impacts mucosal toxicities.

    Article  CAS  PubMed  Google Scholar 

  30. Chera BS, Amdur RJ, Tepper J, Qaqish B, Green R, Aumer SL, et al. Phase 2 trial of de-intensified chemoradiation therapy for favorable-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2015;93:976–85.

    Article  PubMed  Google Scholar 

  31. Chen AM, Felix C, Wang PC, Hsu S, Basehart V, Garst J, et al. Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study. Lancet Oncol. 2017;18:803–11.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Pytlik R, Benes P, Patorkova M, Chocenska E, Gregora E, Prochazka B, et al. Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo controlled study. Bone Marrow Transpl. 2002;30:953–61.

    Article  CAS  Google Scholar 

  33. Okuno SH, Woodhouse CO, Loprinzi CL, Sloan JA, LaVasseur BI, Clemens-Schutjer D, et al. Phase III controlled evaluation of glutamine for decreasing stomatitis in patients receiving fluorouracil (5-FU)-based chemotherapy. Am J Clin Oncol Cancer. 1999;22:258–61.

    Article  CAS  Google Scholar 

  34. Chattopadhyay S, Saha A, Azam M, Mukherjee A, Sur PK. Role of oral glutamine in alleviation and prevention of radiation-induced oral mucositis: a prospective randomized study. South Asian J Cancer. 2014;3:8–12.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Lopez-Vaquero D, Gutierrez-Bayard L, Rodriguez-Ruiz JA, Saldana-Valderas M, Infante-Cossio P. Double-blind randomized study of oral glutamine on the management of radio/chemotherapy-induced mucositis and dermatitis in head and neck cancer. Mol Clin Oncol. 2017;6:931–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. • Elad S, Cheng KKF, Lalla RV. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy (vol 126, pg 4423, 2020). Cancer. 2021;127:3700. This represents the most comprehensive guideline currently available for OM management in cancer patients.

    Google Scholar 

  37. Bourhis J, De Crevoisier R, Abdulkarim B, Deutsch E, Lusinchi A, Luboinski B, et al. A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma. Int J Radiat Oncol. 2000;46:1105–8.

    Article  CAS  Google Scholar 

  38. Brizel DM, Murphy BA, Rosenthal DI, Pandya KJ, Glueck S, Brizel HE, et al. Phase II study of palifermin and concurrent chemoradiation in head and neck squamous cell carcinoma. J Clin Oncol. 2008;26:2489–96.

    Article  CAS  PubMed  Google Scholar 

  39. Eisbruch A. Amifostine in the treatment of head and neck cancer: intravenous administration, subcutaneous administration, or none of the above. J Clin Oncol. 2011;29:119–21.

    Article  PubMed  Google Scholar 

  40. • Anderson CM, Lee CM, Saunders D, Curtis AE, Dunlap N, Nangia C, et al. 2-year outcomes of phase IIb, randomized, double-blind trial Of GC4419 versus placebo to reduce severe oral mucositis due to concurrent radiotherapy and cisplatin for head and neck cancer. Int J Radiat Oncol. 2020;108:E789-E This is a clinical trial of one of the few novel pharmacologic agents which has showed promising results for OM amelioration.

    Article  Google Scholar 

  41. Dastan F, Ameri A, Dodge S, Shishvan HH, Pirsalehi A, Abbasinazari M. Efficacy and safety of propolis mouthwash in management of radiotherapy induced oral mucositis; a randomized, double blind clinical trial. Rep Pract Oncol Radi. 2020;25:969–73.

    Article  Google Scholar 

  42. Lin LC, Que J, Lin LK, Lin FC. 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. 2006;65:745–50.

    Article  CAS  Google Scholar 

  43. Epstein JB, Silverman S Jr, Paggiarino DA, Crockett S, Schubert MM, Senzer NN, 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.

    Article  CAS  PubMed  Google Scholar 

  44. Kazemian A, Kamian S, Aghili M, Hashemi FA, Haddad P. Benzydamine for prophylaxis of radiation-induced oral mucositis in head and neck cancers: a double-blind placebo-controlled randomized clinical trial. Eur J Cancer Care (Engl). 2009;18:174–8.

    Article  CAS  Google Scholar 

  45. Romero-Sandoval EA, McCall C, Eisenach JC. alpha 2-Adrenoceptor stimulation transforms immune responses in neuritis and blocks neuritis-induced pain. J Neurosci. 2005;25:8988–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Attali P, Roulet V, Lyng G, Zakin L, Trochon-Joseph V, Lemarchand C, et al. Effect of topical clonidine on the duration and severity of radiation-induced oral mucositis (OM) in a translational hamster model. J Clin Oncol. 2014;32(15):S10091.

  47. • Giralt J, Tao YG, Kortmann RD, Zasadny X, Contreras-Martinez J, Ceruse P, et al. Randomized phase 2 trial of a novel clonidine mucoadhesive buccal tablet for the amelioration of oral mucositis in patients treated with concomitant chemoradiation therapy for head and neck cancer. Int J Radiat Oncol. 2020;106:320–8. This is an innovative application of a pre-existing pharmacologic agent which has shown promising results in OM amelioration. A larger study is underway which has the potential to advance the practice of OM management.

    Article  CAS  Google Scholar 

  48. Neiburger EJ. Rapid healing of gingival incisions by the helium-neon diode laser. J Mass Dent Soc. 1999;48:8–13 40.

  49. Epstein JB, Thariat J, Bensadoun RJ, Barasch A, Murphy BA, Kolnick L, et al. Oral complications of cancer and cancer therapy from cancer treatment to survivorship. Ca-Cancer J Clin. 2012;62:401–22.

    Article  Google Scholar 

  50. • Zadik Y, Arany PR, Fregnani ER, Bossi P, Antunes HS, Bensadoun RJ, et al. Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019;27:3969–83. While photobiomodulation remains costly and cumbersome to implement, high-volume head and neck cancer treatment centers should be aware of this approach and consider its utilization in select patients at high risk for severe OM.

    Article  PubMed  Google Scholar 

  51. Gautam AP, Fernandes DJ, Vidyasagar MS, Maiya AG, Nigudgi S. Effect of low-level laser therapy on patient reported measures of oral mucositis and quality of life in head and neck cancer patients receiving chemoradiotherapy-a randomized controlled trial. Support Care Cancer. 2013;21:1421–8.

    Article  PubMed  Google Scholar 

  52. Antunes HS, Herchenhorn D, Small IA, Araujo CMM, Viegas CMP, Cabral E, et al. Phase III trial of low-level laser therapy to prevent oral mucositis in head and neck cancer patients treated with concurrent chemoradiation. Radiother Oncol. 2013;109:297–302.

    Article  PubMed  Google Scholar 

  53. Oton-Leite AF, Silva GBL, Morais MO, Silva TA, Leles CR, Valadares MC, et al. Effect of low-level laser therapy on chemoradiotherapy-induced oral mucositis and salivary inflammatory mediators in head and neck cancer patients. Laser Surg Med. 2015;47:296–305.

    Article  Google Scholar 

  54. Shieh SH, Wang ST, Tsai ST, Tseng CC. Mouth care for nasopharyngeal cancer patients undergoing radiotherapy. Oral Oncol. 1997;33:36–41.

    Article  CAS  PubMed  Google Scholar 

  55. Borowski B, Benhamou E, Pico JL, Laplanche A, Margainaud JP, Hayat M. Prevention of oral mucositis in patients treated with high-dose chemotherapy and bone marrow transplantation: a randomised controlled trial comparing two protocols of dental care. Eur J Cancer B Oral Oncol. 1994;30B:93–7.

    Article  CAS  PubMed  Google Scholar 

  56. Spijkervet FK, van Saene HK, van Saene JJ, Panders AK, Vermey A, Mehta DM. Mucositis prevention by selective elimination of oral flora in irradiated head and neck cancer patients. J Oral Pathol Med. 1990;19:486–9.

    Article  CAS  PubMed  Google Scholar 

  57. Symonds RP, McIlroy P, Khorrami J, Paul J, Pyper E, Alcock SR, et al. The reduction of radiation mucositis by selective decontamination antibiotic pastilles: a placebo-controlled double-blind trial. Br J Cancer. 1996;74:312–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Giammarco S, Di Giovanni A, Metafuni E, Chiusolo P, Sica S. A pilot study on the efficacy of Lactobacillus brevis CD2 lozenges in preventing oral mucositis by high-dose chemotherapy with autologous hematopoietic stem cell transplantation. Bone Marrow Transpl. 2016;51:S588–S9.

    Google Scholar 

  59. Mueller BA, Millheim ET, Farrington EA, Brusko C, Wiser TH. Mucositis management-practices for hospitalized-patients - national survey results. J Pain Symptom Manag. 1995;10:510–20.

    Article  CAS  Google Scholar 

  60. Zakrzewska JM, Leeson RM, McLuskey M, Vickers M. The development of patient information leaflets. Care of the mouth after radiotherapy. Gerodontology. 1997;14:48–53.

    Article  CAS  PubMed  Google Scholar 

  61. Alvarino-Martin C, Sarrion-Perez MG. Prevention and treatment of oral mucositis in patients receiving chemotherapy. J Clin Exp Dent. 2014;6:e74–80.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Ferretti GA, Raybould TP, Brown AT, Macdonald JS, Greenwood M, Maruyama Y, et al. Chlorhexidine prophylaxis for chemotherapy- and radiotherapy-induced stomatitis: a randomized double-blind trial. Oral Surg Oral Med Oral Pathol. 1990;69:331–8.

    Article  CAS  PubMed  Google Scholar 

  63. Spijkervet FK, van Saene HK, Panders AK, Vermey A, van Saene JJ, Mehta DM, et al. Effect of chlorhexidine rinsing on the oropharyngeal ecology in patients with head and neck cancer who have irradiation mucositis. Oral Surg Oral Med Oral Pathol. 1989;67:154–61.

    Article  CAS  PubMed  Google Scholar 

  64. Foote RL, Loprinzi CL, Frank AR, O’Fallon JR, Gulavita S, Tewfik HH, et al. Randomized trial of a chlorhexidine mouthwash for alleviation of radiation-induced mucositis. J Clin Oncol. 1994;12:2630–3.

    Article  CAS  PubMed  Google Scholar 

  65. Trotti A, Garden A, Warde P, Symonds P, Langer C, Redman R, 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.

    Article  CAS  PubMed  Google Scholar 

  66. Okuno SH, Foote RL, Loprinzi CL, Gulavita S, Sloan JA, Earle J, et al. A randomized trial of a nonabsorbable antibiotic lozenge given to alleviate radiation-induced mucositis. Cancer. 1997;79:2193–9.

    Article  CAS  PubMed  Google Scholar 

  67. Wijers OB, Levendag PC, Harms ER, Gan-Teng AM, Schmitz PI, Hendriks WD, et al. Mucositis reduction by selective elimination of oral flora in irradiated cancers of the head and neck: a placebo-controlled double-blind randomized study. Int J Radiat Oncol Biol Phys. 2001;50:343–52.

    Article  CAS  PubMed  Google Scholar 

  68. Al-Waili NS. Topical application of natural honey, beeswax and olive oil mixture for atopic dermatitis or psoriasis: partially controlled, single-blinded study. Complement Ther Med. 2003;11:226–34.

    Article  PubMed  Google Scholar 

  69. Efem SEE, Udoh KT, Iwara CI. The Antimicrobial spectrum of honey and its clinical-significance. Infection. 1992;20:227–9.

    Article  CAS  PubMed  Google Scholar 

  70. Biswal BM, Zakaria A, Ahmad NM. Topical application of honey in the management of radiation mucositis. A Preliminary study. Support Care Cancer. 2003;11:242–8.

    Article  PubMed  Google Scholar 

  71. Rashad UM, Al-Gezawy SM, El-Gezawy E, Azzaz AN. Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer. J Laryngol Otol. 2009;123:223–8.

    Article  CAS  PubMed  Google Scholar 

  72. Sio TT, Le-Rademacher JG, Leenstra JL, Loprinzi CL, Rine G, Curtis A, et al. Effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo on radiotherapy-related oral mucositis pain the alliance A221304 Randomized Clinical Trial. Jama J Am Med Assoc. 2019;321:1481–90.

    Article  CAS  Google Scholar 

  73. Cialkowska-Rysz A, Dzierzanowski T. Topical morphine for treatment of cancer-related painful mucosal and cutaneous lesions: a double-blind, placebo-controlled cross-over clinical trial. Arch Med Sci. 2019;15:146–51.

    Article  CAS  PubMed  Google Scholar 

  74. Sarvizadeh M, Hemati S, Meidani M, Ashouri M, Roayaei M, Shahsanai A. Morphine mouthwash for the management of oral mucositis in patients with head and neck cancer. Adv Biomed Res. 2015;4:44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Crawford J, Tomita DK, Mazanet R, Glaspy J, Ozer H. Reduction of oral mucositis by filgrastim (r-metHuG-CSF) in patients receiving chemotherapy. Cytokines Cell Mol Ther. 1999;5:187–93.

    CAS  PubMed  Google Scholar 

  76. Nemunaitis J, Rosenfeld CS, Ash R, Freedman MH, Deeg HJ, Appelbaum F, et al. Phase-III randomized, double-blind placebo-controlled trial of Rhgm-Csf following allogeneic bone-marrow transplantation. Bone Marrow Transpl. 1995;15:949–54.

    CAS  Google Scholar 

  77. Dazzi C, Cariello A, Giovanis P, Monti M, Vertogen B, Leoni M, et al. Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study. Ann Oncol. 2003;14:559–63.

    Article  CAS  PubMed  Google Scholar 

  78. Schneider SB, Nishimura RD, Zimmerman RP, Tran L, Shiplacoff J, Tormey M, et al. Filgrastim (r-metHuG-CSF) and its potential use in the reduction of radiation-induced oropharyngeal mucositis: an interim look at a randomized, double-blind, placebo-controlled trial. Cytokines Cell Mol Ther. 1999;5:175–80.

    CAS  PubMed  Google Scholar 

  79. Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D, Kewalramani T, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. New Engl J Med. 2004;351:2590–8.

    Article  CAS  PubMed  Google Scholar 

  80. Henke M, Alfonsi M, Foa P, Giralt J, Bardet E, Cerezo L, et al. Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy for head and neck cancer: a randomized, placebo-controlled trial. J Clin Oncol. 2011;29:2815–20.

    Article  CAS  PubMed  Google Scholar 

  81. Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, et al. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012;84:1198–205.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393:40–50.

    Article  CAS  PubMed  Google Scholar 

  83. Li K, Yang L, Xin P, Chen Y, Hu QY, Chen XZ, et al. Impact of dose volume parameters and clinical factors on acute radiation oral mucositis for locally advanced nasopharyngeal carcinoma patients treated with concurrent intensity-modulated radiation therapy and chemoradiotherapy. Oral Oncol. 2017;72:32–7.

    Article  PubMed  Google Scholar 

  84. Sanguineti G, Sormani MP, Marur S, Gunn GB, Rao N, Cianchetti M, et al. Effect of radiotherapy and chemotherapy on the risk of mucositis during intensity-modulated radiation therapy for oropharyngeal cancer. Int J Radiat Oncol Biol Phys. 2012;83:235–42.

    Article  PubMed  Google Scholar 

  85. Cheng KK, Molassiotis A, Chang AM, Wai WC, Cheung SS. Evaluation of an oral care protocol intervention in the prevention of chemotherapy-induced oral mucositis in paediatric cancer patients. Eur J Cancer. 2001;37:2056–63.

    Article  CAS  PubMed  Google Scholar 

  86. Dodd MJ, Larson PJ, Dibble SL, Miaskowski C, Greenspan D, MacPhail L, et al. Randomized clinical trial of chlorhexidine versus placebo for prevention of oral mucositis in patients receiving chemotherapy. Oncol Nurs Forum. 1996;23:921–7.

    CAS  PubMed  Google Scholar 

  87. Ertekin MV, Karslioglu I, Erdem F, Sezen O, Gepdiremen A, Serifoglu K. Zinc sulfate in the prevention of total-body irradiation-induced early hematopoietic toxicity - a controlled study in a rat model. Biol Trace Elem Res. 2004;100:63–73.

    Article  CAS  PubMed  Google Scholar 

  88. Yamashita T, Araki K, Tomifuji M, Kamide D, Tanaka Y, Shiotani A. A traditional Japanese medicine-Hangeshashinto (TJ-14)-alleviates chemoradiation-induced mucositis and improves rates of treatment completion. Support Care Cancer. 2015;23:29–35.

    Article  PubMed  Google Scholar 

  89. Anderson CM, Lee CM, Saunders DP, Curtis A, Dunlap N, Nangia C, et al. Phase IIb, randomized, double-blind trial of gc4419 versus placebo to reduce severe oral mucositis due to concurrent radiotherapy and cisplatin for head and neck cancer. J Clin Oncol. 2019;37:3256.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA

    Charles T. Lee MD, PharmD & Thomas J. Galloway MD

Authors
  1. Charles T. Lee MD, PharmD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas J. Galloway MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles T. Lee MD, PharmD.

Ethics declarations

Conflict of interest

Charles T. Lee and Thomas J. Galloway each declare no potential conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Head and Neck Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, C.T., Galloway, T.J. Pathogenesis and Amelioration of Radiation-Induced Oral Mucositis. Curr. Treat. Options in Oncol. 23, 311–324 (2022). https://doi.org/10.1007/s11864-022-00959-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-022-00959-z

Keywords

Search

Navigation