Oral Mucositis in Patients Undergoing Chemotherapy and Radiotherapy: A Review

Yıl 2020, Cilt: 13 Sayı: 3, 185 - 194, 15.07.2020

Seher Çakmak , Nesrin Nural

https://doi.org/10.46483/deuhfed.634402

Cited By: 5

Öz

Oral mucositis is caused by disruption of oral mucosal integrity following chemotherapy and / or radiotherapy. Especially head and neck radiotherapy, antimetabolite and alkylating chemotherapy agents cause an increase the frequency and severity of oral mucositis. In patients with oral mucositis emerges serious complications such as pain in the mouth / throat, infection and bleeding. It may also have clinical and economic consequences such as deterioration in daily living activities, fluid, nutrient and analgesia support, prolonged hospital stay and increased treatment cost. Many pharmacological and non-pharmacological agents are used in the prevention / treatment of oral mucositis. In this review, the definition, epidemiology, developmental mechanism, etiology / risk factors, clinical / economic outcomes, evaluation, prevention/treatment of oral mucositis and the role of nurse will be discussed.

Anahtar Kelimeler

Hematopoietic Stem Cell Transplant, Chemotherapy, Oral Mucositis, Radiotherapy

Kemoterapi ve Radyoterapi Alan Hastalarda Oral Mukozit: Bir Gözden Geçirme

Öz

Oral mukozit, kemoterapi ve/veya radyoterapiyi takiben oral mukoza bütünlüğünün bozulmasıyla ortaya çıkmaktadır. Özellikle baş-boyun bölgesine uygulanan radyoterapi, antimetabolit ve alkilleyici kemoterapi ajanları oral mukozit sıklığında ve şiddetinde artışa neden olmaktadır. Oral mukozit gelişen hastalarda ağız/boğazda ağrı, enfeksiyon ve kanama gibi ciddi komplikasyonlar ortaya çıkmaktadır. Ayrıca günlük yaşam aktivitelerinde bozulma, sıvı, besin ve analjezi desteği, hastanede yatış süresinin uzaması ve tedavi maliyetinde artış gibi klinik ve ekonomik sonuçları olabilmektedir. Oral mukozitin önlenmesi/tedavisinde farmakolojik ve farmakolojik olmayan birçok ajan kullanılmaktadır. Bu derlemede oral mukozitin tanımı, epidemiyolojisi, gelişme mekanizması, etiyolojisi/risk faktörleri, klinik/ekonomik sonuçları, değerlendirilmesi, önlenmesi/tedavisi ve hemşirenin rolü tartışılacaktır.

Anahtar Kelimeler

Hematopoetik Kök Hücre Nakli, Kemoterapi, Oral Mukozit, Radyoterapi

Kaynakça

• 1. Maria OM, Eliopoulos N, Muanza T. Radiation-induced oral mucositis. Front Oncol 2017;7:89.
• 2. Chaudhry HM, Bruce AJ, Wolf RC, Litzow MR, Hogan WJ, Patnaik MS, et al. The incidence and severity of oral mucositis among allogeneic hematopoietic stem cell transplantation patients: a systematic review. Biol Blood Marrow Transplant 2016;22(4):605-616.
• 3. Kamińska M, Juszkiewicz M, Tymicka R, Bronikowska A, Kolak A. Procedure in the prevention and nurturing of inflammatory changes of oral mucositis among patients treated for oncological conditions. Medical Studies/Studia Medyczne. 2016;32(2):145-149.
• 4. Barkokebas A, Silva IHM, De Andrade SC, Carvalho AAT, Gueiros LAM, Paiva SM, et al. Impact of oral mucositis on oral-health-related quality of life of patients diagnosed with cancer. Journal of Oral Pathology & Medicine. 2015;44(9):746-751.
• 5. Schub E, Gilberto C. Stomatitis (Oral mucositis), Cancer treatment-induced. Cinahl Information Systems 2017.
• 6. Wilberg P, Hjermstad MJ, Ottesen S, Herlofson BB. Chemotherapy-associated oral sequelae in patients with cancers outside the head and neck region. J Pain Symptom Manage 2014;48(6):1060-1069.
• 7. Çakmak S, Nural N. Incidence of and risk factors for development of oral mucositis in outpatients undergoing cancer chemotherapy. Int J Nurs Pract 2019;25(1):e12710.
• 8. Mercadante S, Aielli F, Adile C, Ferrera P, Valle A, Fusco F, et al. Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients. Support Care Cancer 2015;23(11):3249-3255.
• 9. Staudenmaier T, Cenzer I, Crispin A, Ostermann H, Berger K. Burden of oral mucositis in stem cell transplant patients—the patients’ perspective. Support Care Cancer 2018;26(5):1577-1584.
• 10. Jo KS, Kim NC. Incidence and factors influencing oral mucositis in patients with hematopoietic stem cell transplantation. J Korean Acad Nurs 2014;44(5):542-551.
• 11. Luitel A, Rimal J, Maharjan IK, Regmee P. Assessment of oral mucositis among patients undergoing radiotherapy for head and neck cancer. Kathmandu Univ Med J 2019;65(1):63-67.
• 12. Bilodeau EA, Lalla RV. Recurrent oral ulceration: Etiology, classification, management, and diagnostic algorithm. Periodontology 2019;80(1):49-60.
• 13. Leite Cavalcanti A, José de Macêdo D, Suely Barros Dantas F, dos Santos Menezes K, Filipe Bezerra Silva D, Alves de Melo Junior W, et al. Evaluation of oral mucositis occurrence in oncologic patients under antineoplastic therapy submitted to the low-level laser coadjuvant therapy. J. Clin. Med 2018;7(5):90.
• 14. Al-Ansari S, Zecha JAEM, Barasch A, de Lange J, Rozema FR, Raber-Durlacher JE. Oral mucositis induced by anticancer therapies. Curr Oral Health Rep 2015;2(4):202-211.
• 15. Moslemi D, Nokhandani AM, Otaghsaraei MT, Moghadamnia Y, Kazemi S, Moghadamnia AA. Management of chemo/radiation-induced oral mucositis in patients with head and neck cancer: A review of the current literature. Radiother Oncol. 2016;120(1):13-20.
• 16. Shouval R, Kouniavsky L, Fein J, Danylesko I, Apel A, Shem-Tov N, et al. Determinants for oral mucositis in allogeneic hematopoietic stem cell transplantation: prospective evaluation and risk analysis. Blood. 2017;130(Supplement 1):3239.
• 17. Sonis ST. Pathobiology of oral mucositis: Novel insights and opportunities. J. Support. Oncol. 2007;5(9 Suppl 4), 3-11.
• 18. Sakellari I, Angelopoulou M, Tsopra O, Dervenoulas I, Tsirigotis P, Spyridonidis A, et al. A prospective study of incidence, clinical and quality of life consequences of oral mucositis post palifermin prophylaxis in patients undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation. Ann Hematol 2015;94(10):1733-1740.
• 19. Valeh M, Kargar M, Mansouri A, Kamranzadeh H, Gholami K, Heidari K, et al. Factors affecting the incidence and severity of oral mucositis following hematopoietic stem cell transplantation. Int J Hematol Oncol Stem Cell Res. 2018;12(2):142-152.
• 20. Saedi HS, Gerami H, Soltanipour S, Habibi AF, Mirhosseyni M, Montazeri S, et al. Frequency of chemoradiotherapy-induced mucositis and related risk factors in patients with the head-and-neck cancers: A survey in the North of Iran. J. Dent. Res 2019;16(5):354-359.
• 21. Gussgard AM, Jokstad A, Wood R, Hope AJ, Tenenbaum H. Symptoms reported by head and neck cancer patients during radiotherapy and association with mucosal ulceration site and size: an observational study. Plos One. 2015;10(6):e0129001.
• 22. Curra M, Soares Junior LAV, Martins MD, Santos PSDS. Chemotherapy protocols and incidence of oral mucositis. An integrative review. Einstein (São Paulo). 2018;16(1):1-9.
• 23. Shumsky A, Bilan E, Sanz E, Petrovskiy F. Oncoxin nutritional supplement in the management of chemotherapy- and/or radiotherapy-associated oral mucositis. Mol Clin Oncol. 2019;10(4):463-468.
• 24. Epstein JB, Saunders DP. Managing oral mucositis in cancer therapy. [online]. 1 Temmuz 2015. http://www.oralhealthgroup.com/features/managing-oral-mucositis-cancer-therapy. 17 Eylül 2019.
• 25. Eduardo FdP, Bezinelli LM, Gobbi MF, Pereira AZ, Vogel C, Hamerschlak N, et al. Impact of oral and gastrointestinal mucositis on body weight alterations during hematopoietic stem cell transplantation. Nutr Cancer 2018;70(2):241-248.
• 26. Pereira NF, Silva PVRD, Fukuoka CY, Michel-Crosato E, Gonçalves AS, Alves FA, et al. Measurement of oral health quality of life among patients who underwent haematopoietic stem-cell transplantation. Braz. Oral Res. 2018;32:e78.
• 27. Kuo CC, Wang RH, Wang HH, Li CH. Meta-analysis of randomized controlled trials of the efficacy of propolis mouthwash in cancer therapy-induced oral mucositis. Support Care Cancer 2018; 26(12):4001-4009.
• 28. Elad S, Raber-Durlacher JE, Brennan MT, Saunders DP, Mank AP, Zadik Y, et al. Basic oral care for hematology–oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT). Support Care Cancer 2015;23(1):223-236.
• 29. Gomes AOF, Silva Junior A, Noce CW, Ferreira M, Maiolino A, Torres SR. The frequency of oral conditions detected in hematology inpatients. Hematol Transfus Cell Ther 2018;40(3):240-244.
• 30. Franco P, Martini S, Di Muzio J, Cavallin C, Arcadipane F, Rampino M, et al. Prospective assessment of oral mucositis and its impact on quality of life and patient-reported outcomes during radiotherapy for head and neck cancer. Medical Oncology. 2017;34(5):81.
• 31. Jehn P, Stier R, Tavassol F, Dittmann J, Zimmerer R, Gellrich NC, et al. Physical and psychological impairments associated with mucositis after oral cancer treatment and their impact on quality of life. Oncol Res Treat 2019;42(6):342-348.
• 32. Olson K, Davies B, Degner L, Neufeld K, Plummer H, Thurston N, et al. Assessing stomatitis: refinement of the Western Consortium for Cancer Nursing Research (WCCNR) stomatitis staging system. Can Oncol Nurs J. 1998;8(3):160-165.
• 33. Baysal E, Sarı D. Hematopoetik kök hücre naklinde oral mukozitin önlemesi, bakımı ve tedavisinde güncel yaklaşımlar: Literatür incelemesi. J. Hum. Sci. 2016;13(3), 5721-5739.
• 34. Tavakoli Ardakani M, Ghassemi S, Mehdizadeh M, Mojab F, Salamzadeh J, Ghassemi S, et al. Evaluating the effect of Matricaria recutita and Mentha piperita herbal mouthwash on management of oral mucositis in patients undergoing hematopoietic stem cell transplantation: A randomized, double blind, placebo controlled clinical trial. Complement Ther Med 2016;29:29-34.
• 35. Sonis ST, Eilers JP, Epstein JB, LeVeque FG, Liggett Jr WH, Mulagha MT, et al. Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Cancer 1999;85(10):2103-2113.
• 36. MASCC/ISOO Mucositis Clinical Practice Guidelines [online]. https://www.mascc.org/mucositis-guidelines. 22.10.2019.
• 37. Hong CHL, Gueiros LA, Fulton JS, Cheng KKF, Kandwal A, Galiti D, et al. Systematic review of basic oral care for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer 2019;27(10):3949-3967.
• 38. Mucositis [online]. https://www.ons.org/pep/mucositis. 27.02.2020.
• 39. Çıtlak K, Kapucu S. Kemoterapi alan hastalarda görülen oral mukozitin önlemesi ve tedavisinde güncel yaklaşımlar: Kanıta dayalı uygulamalar. HUHEMFAD-JOHUFON 2015;2(1):70-77.
• 40. Chitapanarux I, Tungkasamit T, Petsuksiri J, Kannarunimit D, Katanyoo K, Chakkabat C, et al. Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis. Support Care Cancer 2018;26(3):879-886.
• 41. Rastogi M, Khurana R, Revannasiddaiah S, Jaiswal I, Nanda SS, Gupta P, et al. Role of benzydamine hydrochloride in the prevention of oral mucositis in head and neck cancer patients treated with radiotherapy (>50 Gy) with or without chemotherapy. Support Care Cancer. 2017;25(5):1439-1443.
• 42. Sheibani KM, Mafi AR, Moghaddam S, Taslimi F, Amiran A, Ameri A. Efficacy of benzydamine oral rinse in prevention and management of radiation-induced oral mucositis: A double-blind placebo-controlled randomized clinical trial. Asia-Pac J Clin Onco. 2015;11(1):22-27.
• 43. Ariyawardana A, Cheng KKF, Kandwal A, Tilly V, Al-Azri AR, Galiti D, et al. Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer 2019;27(10):3985-3995.
• 44. Chaveli-López B, Bagán-Sebastián JV. Treatment of oral mucositis due to chemotherapy. J Clin Exp Dent 2016;8(2):e201-e209.
• 45. Soylu Özler G, Okuyucu Ş, Akoğlu E. The efficacy of sucralfate and chlorhexidine as an oral rinse in patients with recurrent aphthous stomatitis. Adv Med 2014; doi:10.1155/2014/986203.
• 46. Cardona A, Balouch A, Abdul MM, Sedghizadeh PP, Enciso R. Efficacy of chlorhexidine for the prevention and treatment of oral mucositis in cancer patients: a systematic review with meta-analyses. J Oral Pathol Med 2017;46(9):680-688.
• 47. Ala S, Saeedi M, Janbabai G, Ganji R, Azhdari E, Shiva A. Efficacy of sucralfate mouth wash in prevention of 5-fluorouracil induced oral mucositis: a prospective, randomized, double-blind, controlled trial. Nutr Cancer 2016;68(3):456-463.
• 48. Saunders DP, Rouleau T, Cheng K, Yarom N, Kandwal A, Joy J, et al. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer 2020; 21 (11): 3191-3207.
• 49. Mozaffari HR, Payandeh M, Ramezani M, Sadeghi M, Mahmoudiahmadabadi M, Sharifi R. Efficacy of palifermin on oral mucositis and acute GVHD after hematopoietic stem cell transplantation (HSCT) in hematology malignancy patients: a meta-analysis of trials. Wspolczesna Onkol 2017;21(4):299-305.
• 50. Adil M, Sriram S, Azharuddin M, Ghosh P, Sharma M. PCN4 Effect of palifermin on oral mucositis and acute GVHD after allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancy: a meta-analysis. Value Health 2019;22:56.
• 51. Treister N, Nieder M, Baggott C, Olson E, Chen L, Dang H, et al. Caphosol for prevention of oral mucositis in pediatric myeloablative haematopoietic cell transplantation. Br J Cancer 2016;116:121.
• 52. Murdock JL, Reeves DJ. Chemotherapy-induced oral mucositis management: A retrospective analysis of MuGard, Caphosol, and standard supportive care measures. J Oncol Pharm Pract. 2019;26(3):521-528.
• 53. Svanberg A, Öhrn K, Birgegård G. Caphosol® mouthwash gives no additional protection against oral mucositis compared to cryotherapy alone in stem cell transplantation. A pilot study. Eur J Oncol Nurs. 2015;19(1):50-53.
• 54. Wong KH, Kuciejewska A, Sharabiani MTA, Ng-Cheng-Hin B, Hoy S, Hurley T, et al. A randomised controlled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer. Radiother Oncol. 2017;122(2):207-211.
• 55. Yarom N, Hovan A, Bossi P, Ariyawardana A, Jensen SB, Gobbo M, et al. Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines—part 1: vitamins, minerals, and nutritional supplements. Support Care Cancer. 2019;27(10):3997-4010.
• 56. Rambod M, Pasyar N, Ramzi M. The effect of zinc sulfate on prevention, incidence, and severity of mucositis in leukemia patients undergoing chemotherapy. Eur J Oncol Nurs. 2018;33:14-21.
• 57. Tian X, Liu X-L, Pi Y-P, Chen H, Chen W-Q. Oral zinc sulfate for prevention and treatment of chemotherapy-induced oral mucositis: a meta-analysis of five randomized controlled trials. Front Oncol 2018;8:484.
• 58. Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P. Glutamine: Metabolism and immune function, supplementation and clinical translation. Nutrients. 2018;10(11):1564.
• 59. Sayles C, Hickerson SC, Bhat RR, Hall J, Garey KW, Trivedi MV. Oral glutamine in preventing treatment-related mucositis in adult patients with cancer: a systematic review. Nutr Clin Pract 2016;31(2):171-179.
• 60. Pathak S, Soni TP, Sharma LM, Patni N, Gupta AK. A randomized controlled trial to evaluate the role and efficacy of oral glutamine in the treatment of chemo-radiotherapy-induced oral mucositis and dysphagia in patients with oropharynx and larynx carcinoma. Cureus. 2019; 11 (6): e4855.
• 61. Manzi ND, Silveira R, dos Reis PED. Prophylaxis for mucositis induced by ambulatory chemotherapy: systematic review. J Adv Nurs 2016;72(4):735-746.
• 62. Oberoi S, Zamperlini–Netto G, Beyene J, Treister NS, Sung L. Effect of prophylactic low level laser therapy on oral mucositis: a systematic review and meta-analysis. PLoS one. 2014;9(9):e107418.
• 63. Ferreira B, da Motta Silveira FM, de Orange FA. Low-level laser therapy prevents severe oral mucositis in patients submitted to hematopoietic stem cell transplantation: a randomized clinical trial. Support Care Cancer. 2016;24(3):1035-1042.
• 64. Silva GBL, Sacono NT, Othon-Leite AF, Mendonça EF, Arantes AM, Bariani C, et al. Effect of low-level laser therapy on inflammatory mediator release during chemotherapy-induced oral mucositis: a randomized preliminary study. Lasers Med Sci 2015;30(1):117-126.
• 65. Zadik Y, Arany PR, Fregnani ER, Bossi P, Antunes HS, Bensadoun R-J, et al. Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019;27(10):3969-3983.
• 66. Gholizadeh N, Sheykhbahaei N, Sadrzadeh-Afshar M-S. New treatment approaches of oral mucositis: a review of literature. Adv Hum Biol 2016;6(2):66.
• 67. Park S-H, Han SH. Effect of oral cryotherapy for reducing oral mucositis in hematopoietic stem cell transplantation: a systematic review and meta-analysis. Korean J. Adult Nurs. 2018;30(4):362-375.
• 68. Correa MEP, Cheng KKF, Chiang K, Kandwal A, Loprinzi CL, Mori T, et al. Systematic review of oral cryotherapy for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019;28 (5): 2449-2456.
• 69. Samdariya S, Lewis S, Kauser H, Ahmed I, Kumar D. A randomized controlled trial evaluating the role of honey in reducing pain due to radiation induced mucositis in head and neck cancer patients. Indian J Palliat 2015;21(3):268-273.
• 70. Cho HK, Jeong YM, Lee HS, Lee YJ, Hwang SH. Effects of honey on oral mucositis in patients with head and neck Cancer: A meta-analysis. The Laryngoscope. 2015;125(9):2085-2092.
• 71. Xu JL, Xia R, Sun ZH, Sun L, Min X, Liu C, et al. Effects 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(12):1618-1625.
• 72. Nagi R, Patil DJ, Rakesh N, Jain S, Sahu S. Natural agents in the management of oral mucositis in cancer patients-systematic review. J Oral Biol Craniofac Res 2018;8(3):245-254.
• 73. Raeessi MA, Raeessi N, Panahi Y, Gharaie H, Davoudi SM, Saadat A, et al. “Coffee plus Honey” versus “topical steroid” in the treatment of chemotherapy-induced oral mucositis: a randomised controlled trial. BMC Complement Altern Med 2014;14(1):293.
• 74. Khanjani Pour-Fard-Pachekenari A, Rahmani A, Ghahramanian A, Asghari Jafarabadi M, Onyeka TC, Davoodi A. The effect of an oral care protocol and honey mouthwash on mucositis in acute myeloid leukemia patients undergoing chemotherapy: a single-blind clinical trial. Clin Oral Investig 2019;23(4):1811-1821.
• 75. Przybylek I, Karpinski TM. Antibacterial properties of propolis. Molecules. 2019;24(11):2047.
• 76. Ferreira JM, Fernandes-Silva CC, Salatino A, Negri G, Message D. New propolis type from north-east Brazil: chemical composition, antioxidant activity and botanical origin. J Sci Food Agric. 2017;97(11):3552-3558.
• 77. Kasiotis KM, Anastasiadou P, Papadopoulos A, Machera K. Revisiting Greek Propolis: Chromatographic Analysis and Antioxidant Activity Study. Plos One. 2017;12(1):e0170077.
• 78. Anjum S, Ullah A, Khan K, Attaullah M, Khan H, Ali H, et al. Composition and functional properties of propolis (bee glue): A review. Saudi J Biol Sci 2018;26(7):1695-1703.
• 79. Bolouri AJ, Pakfetrat A, Tonkaboni A, Aledavood SA, Najafi MF, Delavarian Z, et al. Preventing and therapeutic effect of propolis in radiotherapy induced mucositis of head and neck cancers: a triple-blind, randomized, placebo-controlled trial. Iran J Cancer Prev 2015;8(5):e4019.
• 80. Piredda M, Facchinetti G, Biagioli V, Giannarelli D, Armento G, Tonini G, et al. Propolis in the prevention of oral mucositis in breast cancer patients receiving adjuvant chemotherapy: A pilot randomised controlled trial. Eur J Cancer 2017;26(6):1-8.
• 81. Chaitanya NC, Muthukrishnan A, Babu DBG, Kumari CS, Lakshmi MA, Palat G, et al. Role of vitamin E and vitamin A in oral mucositis induced by cancer chemo/radiotherapy- a meta-analysis. J Clin Diagn Res 2017;11(5):4.
• 82. Khurana A, Tekula S, Saifi MA, Venkatesh P, Godugu C. Therapeutic applications of selenium nanoparticles. Biomedicine & Pharmacotherapy. 2019;111:802-812.
• 83. Ameri A, Abbasinazari M, Fazeli A, Sarafzadeh F, Mahboubi A. The effect of oral selenium on radiotherapy induced mucositis in patients with head and neck cancer: a pilot double-blind study. JKMU 2016;23(1):12-20.
• 84. Radha MH, Laxmipriya NP. Evaluation of biological properties and clinical effectiveness of Aloe vera: A systematic review. J Tradit Complement Med 2015;5(1):21-26.
• 85. Aghamohamamdi A, Hosseinimehr SJ. Natural products for management of oral mucositis induced by radiotherapy and chemotherapy. Integr Cancer Ther 2016;15(1):60-68.
• 86. Chen H, Pu J, Liu D, Yu W, Shao Y, Yang G, et al. Anti-inflammatory and antinociceptive properties of flavonoids from the fruits of black mulberry (Morus nigra L.). Plos One. 2016;11(4):e0153080.
• 87. Li Y, Bao T, Chen W. Comparison of the protective effect of black and white mulberry against ethyl carbamate-induced cytotoxicity and oxidative damage. Food Chem 2018;243:65-73.
• 88. Demir Doğan M, Can G, Meral R. Effectiveness of black mulberry molasses in prevention of radiotherapy-induced oral mucositis: a randomized controlled study in head and neck cancer patients. J Altern Complement Med. 2017;23(12):971-979.
• 89. Harman M, Ovayolu N, Ovayolu O. The effect of three different solutions on preventing oral mucositis in cancer patients undergoing stem cell transplantation: a non-randomized controlled trial: A Turkish study-non-randomised trial. J Pak Med Assoc. 2019;69(6):811-816.
• 90. Leppla L, De Geest S, Fierz K, Deschler-Baier B, Koller A. An oral care self-management support protocol (OrCaSS) to reduce oral mucositis in hospitalized patients with acute myeloid leukemia and allogeneic hematopoietic stem cell transplantation: a randomized controlled pilot study. Support Care Cancer. 2016;24(2), 773-782.
• 91. Carvalho CG, Medeiros-Filho JB, Ferreira MC. Guide for health professionals addressing oral care for individuals in oncological treatment based on scientific evidence. Support Care Cancer. 2018;26(8):2651-2661.
• 92. Lopes LD, Rodrigues AB, Brasil DRM, Moreira MMC, Amaral JG, Oliveira PPD. Prevention and treatment of mucositis at an oncology outpatient clinic: a collective construction. Texto & Contexto - Enfermagem. 2016;25(1).
• 93. Avci S, Sari HY. Effect of an evidence-based nursing intervention on the diagnosis of oral mucositis in the pediatric stem cell transplant unit. Asia Pac J Oncol Nurs. 2019;6(3), 292-299.
• 94. Kanagalingam J, Wahid MIA, Lin J-C, Cupino NA, Liu E, Kang J-H, et al. Patient and oncologist perceptions regarding symptoms and impact on quality-of-life of oral mucositis in cancer treatment: results from the Awareness Drives Oral Mucositis PercepTion (ADOPT) study. Support Care Cancer. 2018;26(7):2191-2200.