The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies

Sharon Elad, Noam Yarom, Yehuda Zadik, Michal Kuten-Shorrer, Stephen T Sonis, Sharon Elad, Noam Yarom, Yehuda Zadik, Michal Kuten-Shorrer, Stephen T Sonis

Abstract

Oral mucositis (OM) is a common, highly symptomatic complication of cancer therapy that affects patients' function, quality of life, and ability to tolerate treatment. In certain patients with cancer, OM is associated with increased mortality. Research on the management of OM is ongoing. Oral mucosal toxicities are also reported in targeted and immune checkpoint inhibitor therapies. The objective of this article is to present current knowledge about the epidemiology, pathogenesis, assessment, risk prediction, and current and developing intervention strategies for OM and other ulcerative mucosal toxicities caused by both conventional and evolving forms of cancer therapy.

Keywords: cancer; immune checkpoint inhibitors; immunotherapy; oral mucositis; stomatitis; targeted therapy; toxicity; ulcer.

© 2021 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.

References

    1. Sonis ST, Oster G, Fuchs H, et al. Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol. 2001;19:2201-2205. doi:10.1200/jco.2001.19.8.2201
    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71:7-33. doi:10.3322/caac.21654
    1. Ueno T, Zenda S, Konishi T, et al. The post hoc analysis comparing the severity grades of chemoradiotherapy-induced oral mucositis scored between the central and local assessors in a multicenter, randomized controlled trial of rebamipide for head and neck cancer. Int J Clin Oncol. 2019;24:241-247. doi:10.1007/s10147-018-1355-7
    1. Bellm LA, Epstein JB, Rose-Ped A, Martin P, Fuchs HJ. Patient reports of complications of bone marrow transplantation. Support Care Cancer. 2000;8:33-39. doi:10.1007/s005209900095
    1. Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004;351:2590-2598. doi:10.1056/NEJMoa040125
    1. Vagliano L, Feraut C, Gobetto G, et al. Incidence and severity of oral mucositis in patients undergoing haematopoietic SCT-results of a multicentre study. Bone Marrow Transplant. 2011;46:727-732. doi:10.1038/bmt.2010.184
    1. Chaudhry HM, Bruce AJ, Wolf RC, et al. The incidence and severity of oral mucositis among allogeneic hematopoietic stem cell transplantation patients: a systematic review. Biol Blood Marrow Transplant. 2016;22:605-616. doi:10.1016/j.bbmt.2015.09.014
    1. Garming Legert K, Ringden O, Remberger M, Torlen J, Mattsson J, Dahllof G. Oral mucositis after tacrolimus/sirolimus or cyclosporine/methotrexate as graft-versus-host disease prophylaxis. Oral Dis. 2021;27:1217-1225. doi:10.1111/odi.13663
    1. Berger K, Schopohl D, Bollig A, et al. Burden of oral mucositis: a systematic review and implications for future research. Oncol Res Treat. 2018;41:399-405. doi:10.1159/000487085
    1. Anderson CM, Lee CM, Saunders DP, 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;37:3256-3265. doi:10.1200/jco.19.01507
    1. Szturz P, Wouters K, Kiyota N, et al. Altered fractionation radiotherapy combined with concurrent low-dose or high-dose cisplatin in head and neck cancer: a systematic review of literature and meta-analysis. Oral Oncol. 2018;76:52-60. doi:10.1016/j.oraloncology.2017.11.025
    1. Jones JA, Avritscher EB, Cooksley CD, Michelet M, Bekele BN, Elting LS. Epidemiology of treatment-associated mucosal injury after treatment with newer regimens for lymphoma, breast, lung, or colorectal cancer. Support Care Cancer. 2006;14:505-715. doi:10.1007/s00520-006-0055-4
    1. Curra M, Gabriel AF, Ferreira MBC, et al. Incidence and risk factors for oral mucositis in pediatric patients receiving chemotherapy. Support Care Cancer. 2021;29:6243-6251. doi:10.1007/s00520-021-06199-5
    1. Basile D, Di Nardo P, Corvaja C, et al. Mucosal injury during anti-cancer treatment: from pathobiology to bedside. Cancers (Basel). 2019;11:857.
    1. Sonis ST. Mucositis: The impact, biology and therapeutic opportunities of oral mucositis. Oral Oncol. 2009;45:1015-1020. doi:10.1016/j.oraloncology.2009.08.006
    1. Cinausero M, Aprile G, Ermacora P, et al. New frontiers in the pathobiology and treatment of cancer regimen-related mucosal injury. Front Pharmacol. 2017;8:354. doi:10.3389/fphar.2017.00354
    1. 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;2:202-211.
    1. 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;68:1110-1120.
    1. Vera-Llonch M, Oster G, Ford CM, Lu J, Sonis S. Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies. Support Care Cancer. 2007;15:491-496.
    1. Raber-Durlacher JE, Elad S, Barasch A. Oral mucositis. Oral Oncol. 2010;46:452-456.
    1. Russo G, Haddad R, Posner M, Machtay M. Radiation treatment breaks and ulcerative mucositis in head and neck cancer. Oncologist. 2008;13:886-898. doi:10.1634/theoncologist.2008-0024
    1. Elad S, Zadik Y. Chronic oral mucositis after radiotherapy to the head and neck: a new insight. Support Care Cancer. 2016;24:4825-4830.
    1. Lalla RV, Treister N, Sollecito T, et al. Oral complications at 6 months after radiation therapy for head and neck cancer. Oral Dis. 2017;23:1134-1143.
    1. Wardill HR, Sonis ST, Blijlevens NMA, et al. Prediction of mucositis risk secondary to cancer therapy: a systematic review of current evidence and call to action. Support Care Cancer. 2020;28:5059-5073. doi:10.1007/s00520-020-05579-7
    1. Blijlevens N, Schwenkglenks M, Bacon P, et al. Prospective oral mucositis audit: oral mucositis in patients receiving high-dose melphalan or BEAM conditioning chemotherapy-European Blood and Marrow Transplantation Mucositis Advisory Group. J Clin Oncol. 2008;26:1519-1525. doi:10.1200/jco.2007.13.6028
    1. McCarthy GM, Awde JD, Ghandi H, Vincent M, Kocha WI. Risk factors associated with mucositis in cancer patients receiving 5-fluorouracil. Oral Oncol. 1998;34:484-490. doi:10.1016/s1368-8375(98)00068-2
    1. Li K, Yang L, Xin P, 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;72:32-37. doi:10.1016/j.oraloncology.2017.06.026
    1. Shouval R, Kouniavski E, Fein J, et al. Risk factors and implications of oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation. Eur J Haematol. 2019;103:402-409. doi:10.1111/ejh.13299
    1. Bourhis J, Lapeyre M, Tortochaux J, et al. Phase III randomized trial of very accelerated radiation therapy compared with conventional radiation therapy in squamous cell head and neck cancer: a GORTEC trial. J Clin Oncol. 2006;24:2873-2878. doi:10.1200/jco.2006.08.057
    1. Overgaard J, Hansen HS, Specht L, et al. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet. 2003;362:933-940. doi:10.1016/s0140-6736(03)14361-9
    1. de Farias Gabriel A, Silveira FM, Curra M, et al. Risk factors associated with the development of oral mucositis in pediatric oncology patients: systematic review and meta-analysis. Oral Dis. Published online March 28, 2021. doi:10.1111/odi.13863
    1. Mendonca RM, Araujo M, Levy CE, et al. Oral mucositis in pediatric acute lymphoblastic leukemia patients: evaluation of microbiological and hematological factors. Pediatr Hematol Oncol. 2015;32:322-330. doi:10.3109/08880018.2015.1034819
    1. Bektas-Kayhan K, Kucukhuseyin O, Karagoz G, et al. Is the MDR1 C3435T polymorphism responsible for oral mucositis in children with acute lymphoblastic leukemia? Asian Pac J Cancer Prev. 2012;13:5251-5255. doi:10.7314/apjcp.2012.13.10.5251
    1. Fadda G, Campus G, Luglie P. Risk factors for oral mucositis in paediatric oncology patients receiving alkylant chemotherapy. BMC Oral Health. 2006;6:13. doi:10.1186/1472-6831-6-13
    1. Valer JB, Curra M, Gabriel AF, et al. Oral mucositis in childhood cancer patients receiving high-dose methotrexate: prevalence, relationship with other toxicities and methotrexate elimination. Int J Paediatr Dent. 2021;31:238-246. doi:10.1111/ipd.12718
    1. Sonis ST. The pathobiology of mucositis. Nat Rev Cancer. 2004;4:277-284. doi:10.1038/nrc1318
    1. Sonis ST. New thoughts on the initiation of mucositis. Oral Dis. 2010;16:597-600.
    1. Lalla RV, Brennan MT, Gordon SM, Sonis ST, Rosenthal DI, Keefe DM. Oral mucositis due to high-dose chemotherapy and/or head and neck radiation therapy. J Natl Cancer Inst Monogr. 2019;53:lgz011. doi:10.1093/jncimonographs/lgz011
    1. Mougeot JLC, Stevens CB, Morton DS, Brennan MT, Mougeot FB. Oral microbiome and cancer therapy-induced oral mucositis. J Natl Cancer Inst Monogr. 2019;53:lgz002. doi:10.1093/jncimonographs/lgz002
    1. Sonis ST, Elting LS, Keefe D, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(9 suppl):1995-2025.
    1. World Health Organization (WHO). WHO Handbook for Reporting Results of Cancer Treatment. WHO; 1979.
    1. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0. National Cancer Institute, National Institutes of Health, US Department of Health and Human Services; 2017. Accessed October 14, 2021.
    1. 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 Phys. 1995;31:1341-1346. doi:10.1016/0360-3016(95)00060-C
    1. Sung L, Tomlinson GA, Greenberg ML, et al. Validation of the oral mucositis assessment scale in pediatric cancer. Pediatr Blood Cancer. 2007;49:149-153.
    1. 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. Cancer. 1999;85:2103-2113.
    1. Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin Nurs. 2005;14:798-804. doi:10.1111/j.1365-2702.2005.01121.x
    1. 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;26:1577-1584. doi:10.1007/s00520-017-4000-5
    1. Epstein JB, Beaumont JL, Gwede CK, et al. Longitudinal evaluation of the oral mucositis weekly questionnaire-head and neck cancer, a patient-reported outcomes questionnaire. Cancer. 2007;109:1914-1922.
    1. Stiff P, Erder H, Bensinger W, et al. Reliability and validity of a patient self-administered daily questionnaire to assess impact of oral mucositis (OM) on pain and daily functioning in patients undergoing autologous hematopoietic stem cell transplantation (HSCT). Bone Marrow Transplant. 2006;37:393-401.
    1. List MA, D'Antonio LL, Cella DF, et al. The performance status scale for head and neck cancer patients and the functional assessment of cancer therapy-head and neck scale: a study of utility and validity. Cancer. 1996;77:2294-2301.
    1. Singer S, Amdal CD, Hammerlid E, et al. International validation of the revised European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43: phase IV. Head Neck. 2019;41:1725-1737.
    1. Tomlinson D, Gibson F, Treister N, et al. Challenges of mucositis assessment in children: expert opinion. Eur J Oncol Nurs. 2008;12:469-475. doi:10.1016/j.ejon.2008.05.010
    1. Tomlinson D, Ethier MC, Judd P, et al. Reliability and construct validity of the oral mucositis daily questionnaire in children with cancer. Eur J Cancer. 2011;47:383-388.
    1. Jacobs S, Baggott C, Agarwal R, et al. Validation of the Children's International Mucositis Evaluation Scale (ChIMES) in paediatric cancer and SCT. Br J Cancer. 2013;109:2515-2522. doi:10.1038/bjc.2013.618
    1. Elad S, Raber-Durlacher JE, Brennan MT, 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;23:223-236. doi:10.1007/s00520-014-2378-x
    1. Hong CH, Gueiros LA, Fulton JS, 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;27:3949-3967.
    1. Correa MEP, Cheng KKF, Chiang K, et al. Systematic review of oral cryotherapy for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2020;28:2449-2456.
    1. Zadik Y, Arany PR, Fregnani ER, et al. Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019;27:3969-3983.
    1. Ariyawardana A, Cheng KKF, Kandwal A, 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;27:3985-3995.
    1. Logan RM, Al-Azri AR, Bossi P, et al. Systematic review of growth factors and cytokines for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2020;28:2485-2498.
    1. Yarom N, Hovan A, Bossi P, 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;27:3997-4010.
    1. Yarom N, Hovan A, Bossi P, et al. Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines-part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. Support Care Cancer. 2020;28:2457-2472.
    1. Saunders DP, Rouleau T, Cheng K, 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;28:2473-2484.
    1. Elad S, Cheng KKF, Lalla RV, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2020;126:4423-4431.
    1. Elad S. The MASCC/ISOO mucositis guidelines 2019 update: introduction to the first set of articles. Support Care Cancer. 2019;27:3929-3931. doi:10.1007/s00520-019-04895-x
    1. Elad S. The MASCC/ISOO mucositis guidelines 2019: the second set of articles and future directions. Support Care Cancer. 2020;28:2445-2447. doi:10.1007/s00520-019-05153-w
    1. Miranda-Silva W, Gomes-Silva W, Zadik Y, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis: subanalysis of current interventions for the management of oral mucositis in pediatric cancer patients. Support Care Cancer. 2021;29:3539-3562. doi:10.1007/s00520-020-05803-4
    1. Sung L, Robinson P, Treister N, et al. Guideline for the prevention of oral and oropharyngeal mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation. BMJ Support Palliat Care. 2017;7:7-16.
    1. Rugo HS, Hortobagyi GN, Yao J, et al. Meta-analysis of stomatitis in clinical studies of everolimus: incidence and relationship with efficacy. Ann Oncol. 2016;27:519-525. doi:10.1093/annonc/mdv595
    1. Martins F, de Oliveira MA, Wang Q, et al. A review of oral toxicity associated with mTOR inhibitor therapy in cancer patients. Oral Oncol. 2013;49:293-298. doi:10.1016/j.oraloncology.2012.11.008
    1. Miroddi M, Sterrantino C, Simonelli I, Ciminata G, Phillips RS, Calapai G. Risk of grade 3-4 diarrhea and mucositis in colorectal cancer patients receiving anti-EGFR monoclonal antibodies regimens: a meta-analysis of 18 randomized controlled clinical trials. Crit Rev Oncol Hematol. 2015;96:355-371. doi:10.1016/j.critrevonc.2015.06.004
    1. Abdel-Rahman O, Fouad M. Risk of mucocutaneous toxicities in patients with solid tumors treated with lapatinib: a systematic review and meta-analysis. Curr Med Res Opin. 2015;31:975-986. doi:10.1185/03007995.2015.1020367
    1. Gisondi P, Geat D, Mattiucci A, Lombardo F, Santo A, Girolomoni G. Incidence of adverse cutaneous reactions to epidermal growth factor receptor inhibitors in patients with non-small-cell lung cancer. Dermatology. Published online January 28, 2021. doi:10.1159/000513233
    1. Abdel-Rahman O, Fouad M. Risk of mucocutaneous toxicities in patients with solid tumors treated with sorafenib: an updated systematic review and meta-analysis. Expert Rev Anticancer Ther. 2014;14:751-760. doi:10.1586/14737140.2014.894465
    1. Abdel-Rahman O, Fouad M. Risk of mucocutaneous toxicities in patients with solid tumors treated with sunitinib: a critical review and meta analysis. Expert Rev Anticancer Ther. 2015;15:129-141. doi:10.1586/14737140.2015.985660
    1. Sonis S, Treister N, Chawla S, Demetri G, Haluska F. Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients. Cancer. 2010;116:210-215. doi:10.1002/cncr.24696
    1. Vigarios E, Epstein JB, Sibaud V. Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors. Support Care Cancer. 2017;25:1713-1739. doi:10.1007/s00520-017-3629-4
    1. Singer S, Tan SY, Dewan AK, et al. Cutaneous eruptions from ibrutinib resembling EGFR inhibitor-induced dermatologic adverse events. J Am Acad Dermatol. Published online December 20, 2019. doi:10.1016/j.jaad.2019.12.031
    1. Yuan A, Kurtz SL, Barysauskas CM, Pilotte AP, Wagner AJ, Treister NS. Oral adverse events in cancer patients treated with VEGFR-directed multitargeted tyrosine kinase inhibitors. Oral Oncol. 2015;51:1026-1033.
    1. Boers-Doets CB, Epstein JB, Raber-Durlacher JE, et al. Oral adverse events associated with tyrosine kinase and mammalian target of rapamycin inhibitors in renal cell carcinoma: a structured literature review. Oncologist. 2012;17:135-144.
    1. Lee W, Lee J, Chang S, et al. Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. Br J Dermatol. 2009;161:1045-1051.
    1. Plemons JM, Al-Hashimi I, Marek CL, American Dental Association Council on Scientific A. Managing xerostomia and salivary gland hypofunction: executive summary of a report from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc. 2014;145:867-873. doi:10.14219/jada.2014.44
    1. Mignogna MD, Fortuna G, Leuci S, Pollio A, Ruoppo E. Sunitinib adverse event: oral bullous and lichenoid mucositis. Ann Pharmacother. 2009;43:546-547. doi:10.1345/aph.1L592
    1. Lacouture ME, Maitland ML, Segaert S, et al. A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC Skin Toxicity Study Group. Support Care Cancer. 2010;18:509-522.
    1. Peterson DE, O'Shaughnessy JA, Rugo HS, et al. Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice. Cancer Med. 2016;5:1897-1907.
    1. Peterson D, Boers-Doets C, Bensadoun R, Herrstedt J. Management of oral and gastrointestinal mucosal injury: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2015;26:v139-v151.
    1. Elad S, Zinchuk K, Li S, Cutler C, Liesveld J, Treister NS. Economic and practical considerations in the treatment of oral mucosal chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2018;24:1748-1753. doi:10.1016/j.bbmt.2018.02.022
    1. de Oliveira MA, Martins EMF, Wang Q, et al. Clinical presentation and management of mTOR inhibitor-associated stomatitis. Oral Oncol. 2011;47:998-1003. doi:10.1016/j.oraloncology.2011.08.009
    1. Rugo HS, Seneviratne L, Beck JT, et al. Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial. Lancet Oncol. 2017;18:654-662.
    1. Fantozzi PJ, Treister N, Shekar R, Woo SB, Villa A. Intralesional triamcinolone acetonide therapy for inflammatory oral ulcers. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;128:485-490. doi:10.1016/j.oooo.2019.07.024
    1. Yang W, Li S, Yang Q. Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2019;98:e15731. doi:10.1097/md.0000000000015731
    1. Xu Y, Wen N, Sonis ST, Villa A. Oral side effects of immune checkpoint inhibitor therapy (ICIT): an analysis of 4683 patients receiving ICIT for malignancies at Massachusetts General Hospital, Brigham & Women's Hospital, and the Dana-Farber Cancer Institute, 2011 to 2019. Cancer. 2021;127:1796-1804. doi:10.1002/cncr.33436
    1. Wongvibulsin S, Pahalyants V, Kalinich M, et al. Epidemiology and risk factors for the development of cutaneous toxicities in patients treated with immune-checkpoint inhibitors: a United States population-level analysis. J Am Acad Dermatol. Published online April 2, 2021. doi:10.1016/j.jaad.2021.03.094
    1. Shazib MA, Woo SB, Sroussi H, et al. Oral immune-related adverse events associated with PD-1 inhibitor therapy: a case series. Oral Dis. 2020;26:325-333.
    1. Sibaud V, Eid C, Belum VR, et al. Oral lichenoid reactions associated with anti-PD-1/PD-L1 therapies: clinicopathological findings. J Eur Acad Dermatol Venereol. 2017;31:e464-e469. doi:10.1111/jdv.14284
    1. Gnanendran SS, Turner LM, Miller JA, Hwang SJE, Miller AC. Cutaneous adverse events of anti-PD-1 therapy and BRAF inhibitors. Curr Treat Options Oncol. 2020;21:29. doi:10.1007/s11864-020-0721-7
    1. Sibaud V, Vigarios E, Siegfried A, Bost C, Meyer N, Pages-Laurent C. Nivolumab-related mucous membrane pemphigoid. Eur J Cancer. 2019;121:172-176. doi:10.1016/j.ejca.2019.08.030
    1. Fassler M, Rammlmair A, Feldmeyer L, et al. Mucous membrane pemphigoid and lichenoid reactions after immune checkpoint inhibitors: common pathomechanisms. J Eur Acad Dermatol Venereol. 2020;34:e112-e115.
    1. Dasanu CA. Late-onset Stevens-Johnson syndrome due to nivolumab use for hepatocellular carcinoma. J Oncol Pharm Pract. 2019;25:2052-2055.
    1. Muntyanu A, Netchiporouk E, Gerstein W, Gniadecki R, Litvinov IV. Cutaneous immune-related adverse events (irAEs) to immune checkpoint inhibitors: a dermatology perspective on management. J Cutan Med Surg. 2021;25:59-76. doi:10.1177/1203475420943260
    1. Cappelli LC, Gutierrez AK, Baer AN, et al. Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. Ann Rheum Dis. 2017;76:43-50.
    1. Warner BM, Baer AN, Lipson EJ, et al. Sicca syndrome associated with immune checkpoint inhibitor therapy. Oncologist. 2019;24:1259-1269.
    1. Lacouture M, Sibaud V. Toxic side effects of targeted therapies and immunotherapies affecting the skin, oral mucosa, hair, and nails. Am J Clin Dermatol. 2018;19(suppl 1):31-39. doi:10.1007/s40257-018-0384-3
    1. Ventola CL. Cancer immunotherapy, part 2: efficacy, safety, and other clinical considerations. P T. 2017;42:452-463.
    1. Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158-168. doi:10.1056/NEJMra1703481
    1. Inno A, Metro G, Bironzo P, et al. Pathogenesis, clinical manifestations and management of immune checkpoint inhibitors toxicity. Tumori. 2017;103:405-421.
    1. Geisler AN, Phillips GS, Barrios DM, et al. Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol. 2020;83:1255-1268.
    1. Rapoport BL, Anderson R, Cooksley T, Johnson DB. MASCC 2020 recommendations for the management of immune-related adverse events of patients undergoing treatment with immune checkpoint inhibitors. Support Care Cancer. 2020;28:6107-6110. doi:10.1007/s00520-020-05727-z
    1. Haanen JBAG, Carbonnel F, Robert C, et al. ESMO Guidelines Committee. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2017;28:iv119-iv142.
    1. Arnaud-Coffin P, Maillet D, Gan HK, et al. A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors. Int J Cancer. 2019;145:639-648.
    1. Klein BA, Alves FA, de Santana Rodrigues Velho J, et al. Oral manifestations of immune-related adverse events in cancer patients treated with immune checkpoint inhibitors. Oral Dis. Published online July 15, 2021. doi:10.1111/odi.13964
    1. Rapoport BL, van Eeden R, Sibaud V, et al. Supportive care for patients undergoing immunotherapy. Support Care Cancer. 2017;25:3017-3030. doi:10.1007/s00520-017-3802-9
    1. Sonis ST. Treatment for oral mucositis-current options and an update of small molecules under development. Curr Treat Options Oncol. 2021;22:25. doi:10.1007/s11864-021-00823-6
    1. Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol. 2013;53:401-426. doi:10.1146/annurev-pharmtox-011112-140320
    1. Innovation Pharmaceuticals, Inc. Innovation Pharmaceuticals Phase 2 Oral Mucositis Trial Additional Data Show Brilacidin-OM Demonstrated a Significant Reduction in the Incidence of Severe Oral Mucositis [press release]. Innovation Pharmaceuticals, Inc; 2018. Accessed October 14, 2021.
    1. Innovation Pharmaceuticals, Inc. Study of the Effects of Brilacidin Oral Rinse on Radiation-Induced Oral Mucositis in Patients With Head and Neck Cancer (Brilacidin). identifier NCT02324335. Accessed September 20, 2021.
    1. Giralt J, Tao Y, Kortmann RD, 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 Biol Phys. 2020;106:320-328. doi:10.1016/j.ijrobp.2019.10.023
    1. Elting LS, Chang YC. Costs of oral complications of cancer therapies: estimates and a blueprint for future study. J Natl Cancer Inst Monogr. 2019;53:lgz010. doi:10.1093/jncimonographs/lgz010
    1. Lopes Martins AF, Nogueira TE, Morais MO, et al. Cost-effectiveness randomized clinical trial on the effect of photobiomodulation therapy for prevention of radiotherapy-induced severe oral mucositis in a Brazilian cancer hospital setting. Support Care Cancer. 2021;29:1245-1256. doi:10.1007/s00520-020-05607-6

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