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Oral Mucositis

Abstract

Mucositis is a generalized term used to denote either oral or gastrointestinal mucositis as a consequence of cancer therapy. This chapter will describe the epidemiology of mucositis in relation to radiation therapy for head and neck cancers, chemotherapy, and hematopoietic stem cell transplantation. Clinical features, risk factors and pathogenesis of mucositis are covered in depth. In addition, the current consensus on mucositis management and economic consequences are reviewed in this chapter. Although considered to have a different pathogenesis, targeted therapy related oral mucosal adverse effects are often referred in the literature as mucositis or stomatitis. This entity is described in this chapter, too.

Keywords

  • Oral mucositis
  • Gastrointestinal mucositis
  • Chemotherapy
  • Radiation therapy
  • Targeted therapy
  • HSCT

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Fig. 5.1
Fig. 5.2

Bibliography

  1. Scully C, Sonis S, Diz PD. Oral mucositis. Oral Dis. 2006;12(3):229–41.

    PubMed  Google Scholar 

  2. Basu B, Eisen T. Perspectives in drug development for metastatic renal cell cancer. Target Oncol. 2010;5(2):139–56.

    PubMed  Google Scholar 

  3. Harris M. Monoclonal antibodies as therapeutic agents for cancer. Lancet Oncol. 2004;5(5):292–302.

    PubMed  Google Scholar 

  4. Herbst RS, Shin DM. Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: a new paradigm for cancer therapy. Cancer. 2002;94(5):1593–611.

    PubMed  Google Scholar 

  5. John AM, Thomas NS, Mufti GJ, Padua RA. Targeted therapies in myeloid leukemia. Semin Cancer Biol. 2004;14(1):41–62.

    PubMed  Google Scholar 

  6. Moon C, Chae YK, Lee J. Targeting epidermal growth factor receptor in head and neck cancer: lessons learned from cetuximab. Exp Biol Med. 2010;235(8):907–20.

    Google Scholar 

  7. Mukai H. Targeted therapy in breast cancer: current status and future directions. Jpn J Clin Oncol. 2010;40(8):711–6.

    PubMed  Google Scholar 

  8. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–78.

    PubMed  Google Scholar 

  9. Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov. 2010;9(4):325–38.

    PubMed  Google Scholar 

  10. Watters AL, Epstein JB, Agulnik M. Oral complications of targeted cancer therapies: a narrative literature review. Oral Oncol. 2011;47(6):441–8.

    PubMed  Google Scholar 

  11. Bellm LA, Epstein JB, Rose-Ped A, Martin P, Fuchs HJ. Patient reports of complications of bone marrow transplantation. Support Care Cancer. 2000;8(1):33–9.

    PubMed  Google Scholar 

  12. Stiff P. Mucositis associated with stem cell transplantation: current status and innovative approaches to management. Bone Marrow Transplant. 2001;27(2):S3–S11.

    PubMed  Google Scholar 

  13. 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(11):3233–41.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  15. Niscola P, Romani C, Cupelli L, Scaramucci L, Tendas A, Dentamaro T, et al. Mucositis in patients with hematologic malignancies: an overview. Haematologica. 2007;92(2):222–31.

    PubMed  Google Scholar 

  16. Peterson DE, Lalla RV. Oral mucositis: the new paradigms. Curr Opin Oncol. 2010;22(4):318–22.

    PubMed  PubMed Central  Google Scholar 

  17. Peterson DE, Srivastava R, Lalla RV. Oral mucosal injury in oncology patients: perspectives on maturation of a field. Oral Dis. 2015;21(2):133–41.

    PubMed  Google Scholar 

  18. Logan RM. Advances in understanding of toxicities of treatment for head and neck cancer. Oral Oncol. 2009;45(10):844–8.

    PubMed  Google Scholar 

  19. Sonis ST. Regimen-related gastrointestinal toxicities in cancer patients. Curr Opin Support Palliat Care. 2010;4(1):26–30.

    PubMed  Google Scholar 

  20. Romesser PB, Cahlon O, Scher ED, Hug EB, Sine K, DeSelm C, et al. Proton beam reirradiation for recurrent head and neck cancer: multi-institutional report on feasibility and early outcomes. Int J Radiat Oncol Biol Phys. 2016;95(1):386–95.

    PubMed  PubMed Central  Google Scholar 

  21. Bonner JA, Giralt J, Harari PM, Baselga J, Spencer S, Bell D, et al. Association of human papillomavirus and p16 status with mucositis and dysphagia for head and neck cancer patients treated with radiotherapy with or without cetuximab: assessment from a phase 3 registration trial. Eur J Cancer. 2016;64:1–11.

    PubMed  PubMed Central  Google Scholar 

  22. Guo R, Tang LL, Mao YP, Zhou GQ, Qi ZY, Liu LZ, et al. Clinical outcomes of volume-modulated arc therapy in 205 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. PLoS One. 2015;10(7):e0129679.

    PubMed  PubMed Central  Google Scholar 

  23. Hu MH, Wang LW, Lu HJ, Chu PY, Tai SK, Lee TL, et al. Cisplatin-based chemotherapy versus cetuximab in concurrent chemoradiotherapy for locally advanced head and neck cancer treatment. Biomed Res Int. 2014;904341(10):6.

    Google Scholar 

  24. Lin L, Yao JJ, Zhou GQ, Guo R, Zhang F, Zhang Y, et al. The efficacy and toxicity of individualized intensity-modulated radiotherapy based on the tumor extension patterns of nasopharyngeal carcinoma. Oncotarget. 2016;7(15):20680–90.

    PubMed  PubMed Central  Google Scholar 

  25. Manas A, Palacios A, Contreras J, Sanchez-Magro I, Blanco P, Fernandez-Perez C. Incidence of oral mucositis, its treatment and pain management in patients receiving cancer treatment at Radiation Oncology Departments in Spanish hospitals (MUCODOL Study). Clin Transl Oncol. 2009;11(10):669–76.

    PubMed  Google Scholar 

  26. Vatca M, Lucas JT Jr, Laudadio J, D’Agostino RB, Waltonen JD, Sullivan CA, et al. Retrospective analysis of the impact of HPV status and smoking on mucositis in patients with oropharyngeal squamous cell carcinoma treated with concurrent chemotherapy and radiotherapy. Oral Oncol. 2014;50(9):869–76.

    PubMed  PubMed Central  Google Scholar 

  27. Peterson DE, Bensadoun RJ, Roila F. Management of oral and gastrointestinal mucositis: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22(6):vi78–84.

    PubMed  PubMed Central  Google Scholar 

  28. Trotti A, Bellm LA, Epstein JB, Frame D, Fuchs HJ, Gwede CK, et al. Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol. 2003;66(3):253–62.

    PubMed  Google Scholar 

  29. Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120(10):1453–61.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  31. Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(9 Suppl):1995–2025.

    PubMed  Google Scholar 

  32. Scully C, Epstein J, Sonis S. Oral mucositis: a challenging complication of radiotherapy, chemotherapy, and radiochemotherapy: Part 1, Pathogenesis and prophylaxis of mucositis. Head Neck. 2003;25(12):1057–70.

    PubMed  Google Scholar 

  33. Nishimura N, Nakano K, Ueda K, Kodaira M, Yamada S, Mishima Y, et al. Prospective evaluation of incidence and severity of oral mucositis induced by conventional chemotherapy in solid tumors and malignant lymphomas. Support Care Cancer. 2012;20(9):2053–9.

    PubMed  Google Scholar 

  34. Raber-Durlacher JE, Weijl NI, Abu Saris M, de Koning B, Zwinderman AH, Osanto S. Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases. Support Care Cancer. 2000;8(5):366–71.

    PubMed  Google Scholar 

  35. Tachi T, Teramachi H, Tanaka K, Asano S, Osawa T, Kawashima A, et al. The impact of outpatient chemotherapy-related adverse events on the quality of life of breast cancer patients. PLoS One. 2015;10(4):e0124169.

    PubMed  PubMed Central  Google Scholar 

  36. Wuketich S, Hienz SA, Marosi C. Prevalence of clinically relevant oral mucositis in outpatients receiving myelosuppressive chemotherapy for solid tumors. Support Care Cancer. 2012;20(1):175–83.

    PubMed  Google Scholar 

  37. 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):3249–55.

    PubMed  Google Scholar 

  38. 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(6):505–15.

    PubMed  Google Scholar 

  39. Schwab M, Zanger UM, Marx C, Schaeffeler E, Klein K, Dippon J, et al. Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group. J Clin Oncol. 2008;26(13):2131–8.

    PubMed  Google Scholar 

  40. Wilkes JD. Prevention and treatment of oral mucositis following cancer chemotherapy. Semin Oncol. 1998;25(5):538–51.

    PubMed  Google Scholar 

  41. Peterson DE. Oral toxicity of chemotherapeutic agents. Semin Oncol. 1992;19(5):478–91.

    PubMed  Google Scholar 

  42. Seto BG, Kim M, Wolinsky L, Mito RS, Champlin R. Oral mucositis in patients undergoing bone marrow transplantation. Oral Surg Oral Med Oral Pathol. 1985;60(5):493–7.

    PubMed  Google Scholar 

  43. Zerbe MB, Parkerson SG, Ortlieb ML, Spitzer T. Relationships between oral mucositis and treatment variables in bone marrow transplant patients. Cancer Nurs. 1992;15(3):196–205.

    PubMed  Google Scholar 

  44. Barasch A, Peterson DE, Tanzer JM, D’Ambrosio JA, Nuki K, Schubert MM, et al. Helium-neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients. Cancer. 1995;76(12):2550–6.

    PubMed  Google Scholar 

  45. Mattsson T, Heimdahl A, Dahllof G, Nilsson B, Lonnqvist B, Ringden O. Variables predicting oral mucosal lesions in allogenic bone marrow recipients. Head Neck. 1991;13(3):224–9.

    PubMed  Google Scholar 

  46. Woo SB, Sonis ST, Monopoli MM, Sonis AL. A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients. Cancer. 1993;72(5):1612–7.

    PubMed  Google Scholar 

  47. Peterson DE, Schubert MM. Oral toxicity. In: Perry MC, editor. The chemotherapy source book. 3rd ed. Baltimore: Williams and Wilkins; 2001.

    Google Scholar 

  48. Ahmed T, Engelking C, Szalyga J, Helson L, Coombe N, Cook P, et al. Propantheline prevention of mucositis from etoposide. Bone Marrow Transplant. 1993;12(2):131–2.

    PubMed  Google Scholar 

  49. Oblon DJ, Paul SR, Oblon MB, Malik S. Propantheline protects the oral mucosa after high-dose ifosfamide, carboplatin, etoposide and autologous stem cell transplantation. Bone Marrow Transplant. 1997;20(11):961–3.

    PubMed  Google Scholar 

  50. Barasch A, Peterson DE. Risk factors for ulcerative oral mucositis in cancer patients: unanswered questions. Oral Oncol. 2003;39(2):91–100.

    PubMed  Google Scholar 

  51. Sonis ST. Mucositis: the impact, biology and therapeutic opportunities of oral mucositis. Oral Oncol. 2009;45(12):1015–20.

    PubMed  Google Scholar 

  52. Martinez JM, Pereira D, Chacim S, Mesquita E, Sousa I, Martins A, et al. Mucositis care in acute leukemia and non-Hodgkin lymphoma patients undergoing high-dose chemotherapy. Support Care Cancer. 2014;22(9):2563–9.

    PubMed  Google Scholar 

  53. Friedenberg WR, Miller HJ, Marx JJ Jr, Schloesser LL, Reding DJ, Mazza JJ, et al. The treatment of older adult patients with acute myeloid leukemia by triple infusion chemotherapy. Am J Clin Oncol. 1995;18(2):105–10.

    PubMed  Google Scholar 

  54. Pea F, Russo D, Michieli M, Damiani D, Fanin R, Michelutti A, et al. Disposition of liposomal daunorubicin during cotreatment with cytarabine in patients with leukaemia. Clin Pharmacokinet. 2003;42(9):851–62.

    PubMed  Google Scholar 

  55. Ferrara F, Palmieri S, Pocali B, Pollio F, Viola A, Annunziata S, et al. De novo acute myeloid leukemia with multilineage dysplasia: treatment results and prognostic evaluation from a series of 44 patients treated with fludarabine, cytarabine and G-CSF (FLAG). Eur J Haematol. 2002;68(4):203–9.

    PubMed  Google Scholar 

  56. Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, et al. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003;82(4):231–5.

    PubMed  Google Scholar 

  57. Girmenia C, Lo Coco F, Breccia M, Latagliata R, Spadea A, D’Andrea M, et al. Infectious complications in patients with acute promyelocytic leukaemia treated with the AIDA regimen. Leukemia. 2003;17(5):925–30.

    PubMed  Google Scholar 

  58. Testi AM, Biondi A, Lo Coco F, Moleti ML, Giona F, Vignetti M, et al. GIMEMA-AIEOPAIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia (APL) in children. Blood. 2005;106(2):447–53.

    PubMed  Google Scholar 

  59. Mazza P, Zinzani PL, Martelli M, Fiacchini M, Bocchia M, Pileri S, et al. MACOP-B vs F-MACHOP regimen in the treatment of high-grade non-Hodgkin’s lymphomas. Leuk Lymphoma. 1995;16(5–6):457–63.

    PubMed  Google Scholar 

  60. Milone G, Di Raimondo F, Gioi FL, Palumbo GA, Manenti GO, Pafumi M, et al. Alternation of epirubicin and mitoxantrone in CHOP-like regimens retains efficacy and reduces overall toxicity in elderly patients with high and intermediate grade non-Hodgkin lymphomas. Leuk Lymphoma. 2002;43(12):2319–24.

    PubMed  Google Scholar 

  61. Osby E, Hagberg H, Kvaloy S, Teerenhovi L, Anderson H, Cavallin-Stahl E, et al. CHOP is superior to CNOP in elderly patients with aggressive lymphoma while outcome is unaffected by filgrastim treatment: results of a Nordic Lymphoma Group randomized trial. Blood. 2003;101(10):3840–8.

    PubMed  Google Scholar 

  62. Johnson PW, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS, et al. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin’s lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol. 2005;23(36):9208–18.

    PubMed  Google Scholar 

  63. Bearman SI, Appelbaum FR, Buckner CD, Petersen FB, Fisher LD, Clift RA, et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol. 1988;6(10):1562–8.

    PubMed  Google Scholar 

  64. McGuire DB, Altomonte V, Peterson DE, Wingard JR, Jones RJ, Grochow LB. Patterns of mucositis and pain in patients receiving preparative chemotherapy and bone marrow transplantation. Oncol Nurs Forum. 1993;20(10):1493–502.

    PubMed  Google Scholar 

  65. Pico JL, Avila-Garavito A, Naccache P. Mucositis: its occurrence, consequences, and treatment in the oncology setting. Oncologist. 1998;3(6):446–51.

    PubMed  Google Scholar 

  66. 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):605–16.

    PubMed  Google Scholar 

  67. McCann S, Schwenkglenks M, Bacon P, Einsele H, D’Addio A, Maertens J, et al. The Prospective Oral Mucositis Audit: relationship of severe oral mucositis with clinical and medical resource use outcomes in patients receiving high-dose melphalan or BEAM-conditioning chemotherapy and autologous SCT. Bone Marrow Transplant. 2009;43(2):141–7.

    PubMed  Google Scholar 

  68. Vagliano L, Feraut C, Gobetto G, Trunfio A, Errico A, Campani V, et al. Incidence and severity of oral mucositis in patients undergoing haematopoietic SCT—results of a multicentre study. Bone Marrow Transplant. 2011;46(5):727–32.

    PubMed  Google Scholar 

  69. Stiff PJ, Erder H, Bensinger WI, Emmanouilides C, Gentile T, Isitt J, 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(4):393–401.

    PubMed  Google Scholar 

  70. Bolwell BJ, Kalaycio M, Sobecks R, Andresen S, Kuczkowski E, Bernhard L, et al. A multivariable analysis of factors influencing mucositis after autologous progenitor cell transplantation. Bone Marrow Transplant. 2002;30(9):587–91.

    PubMed  Google Scholar 

  71. Wardley AM, Jayson GC, Swindell R, Morgenstern GR, Chang J, Bloor R, et al. Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. Br J Haematol. 2000;110(2):292–9.

    PubMed  Google Scholar 

  72. Cutler C, Li S, Kim HT, Laglenne P, Szeto KC, Hoffmeister L, et al. Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens. Biol Blood Marrow Transplant. 2005;11(5):383–8.

    PubMed  Google Scholar 

  73. Ferrara F, Palmieri S, De Simone M, Sagristani M, Viola A, Pocali B, et al. High-dose idarubicin and busulphan as conditioning to autologous stem cell transplantation in adult patients with acute myeloid leukaemia. Br J Haematol. 2005;128(2):234–41.

    PubMed  Google Scholar 

  74. Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, et al. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial. Blood. 2002;99(3):731–5.

    PubMed  Google Scholar 

  75. Palumbo A, Bringhen S, Petrucci MT, Musto P, Rossini F, Nunzi M, et al. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial. Blood. 2004;104(10):3052–7.

    PubMed  Google Scholar 

  76. Wang EH, Chen YA, Corringham S, Bashey A, Holman P, Ball ED, et al. High-dose CEB vs BEAM with autologous stem cell transplant in lymphoma. Bone Marrow Transplant. 2004;34(7):581–7.

    PubMed  Google Scholar 

  77. Rapoport AP, Miller Watelet LF, Linder T, Eberly S, Raubertas RF, Lipp J, et al. Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants. J Clin Oncol. 1999;17(8):2446–53.

    PubMed  Google Scholar 

  78. Grazziutti ML, Dong L, Miceli MH, Krishna SG, Kiwan E, Syed N, et al. Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model. Bone Marrow Transplant. 2006;38(7):501–6.

    PubMed  Google Scholar 

  79. Jones JA, Qazilbash MH, Shih YC, Cantor SB, Cooksley CD, Elting LS. In-hospital complications of autologous hematopoietic stem cell transplantation for lymphoid malignancies: clinical and economic outcomes from the Nationwide Inpatient Sample. Cancer. 2008;112(5):1096–105.

    PubMed  Google Scholar 

  80. Martino M, Montanari M, Ferrara F, Ciceri F, Scortechini I, Palmieri S, et al. Very low rate of readmission after an early discharge outpatient model for autografting in multiple myeloma patients: an Italian multicenter retrospective study. Biol Blood Marrow Transplant. 2014;20(7):1026–32.

    PubMed  Google Scholar 

  81. Gupta V, Panzarella T, Li L, Khan J, Sharma A, Lipton JH, et al. A prospective study comparing the outcomes and health-related quality of life in adult patients with myeloid malignancies undergoing allogeneic transplantation using myeloablative or reduced-intensity conditioning. Biol Blood Marrow Transplant. 2012;18(1):113–24.

    PubMed  Google Scholar 

  82. Kashiwazaki H, Matsushita T, Sugita J, Shigematsu A, Kasashi K, Yamazaki Y, et al. A comparison of oral mucositis in allogeneic hematopoietic stem cell transplantation between conventional and reduced-intensity regimens. Support Care Cancer. 2012;20(5):933–9.

    PubMed  Google Scholar 

  83. Urbain P, Raynor A, Bertz H, Lambert C, Biesalski HK. Role of antioxidants in buccal mucosa cells and plasma on the incidence and severity of oral mucositis after allogeneic haematopoietic cell transplantation. Support Care Cancer. 2012;20(8):1831–8.

    PubMed  Google Scholar 

  84. 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(5):491–6.

    PubMed  Google Scholar 

  85. Johansson JE, Brune M, Ekman T. The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell transplantation with reduced intensity conditioning. Bone Marrow Transplant. 2001;28(8):737–42.

    PubMed  Google Scholar 

  86. Legert KG, Remberger M, Ringden O, Heimdahl A, Dahllof G. Reduced intensity conditioning and oral care measures prevent oral mucositis and reduces days of hospitalization in allogeneic stem cell transplantation recipients. Support Care Cancer. 2014;22(8):2133–40.

    PubMed  Google Scholar 

  87. Anand A, Anandi P, Jain NA, Lu K, Dunavin N, Hourigan CS, et al. CD34+ selection and the severity of oropharyngeal mucositis in total body irradiation-based allogeneic stem cell transplantation. Support Care Cancer. 2016;24(2):815–22.

    PubMed  Google Scholar 

  88. Takahashi K, Soga Y, Murayama Y, Udagawa M, Nishimoto H, Sugiura Y, et al. Oral mucositis in patients receiving reduced-intensity regimens for allogeneic hematopoietic cell transplantation: comparison with conventional regimen. Support Care Cancer. 2010;18(1):115–9.

    PubMed  Google Scholar 

  89. Baselga J, Arteaga CL. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol. 2005;23(11):2445–59.

    PubMed  Google Scholar 

  90. Chan KC, Knox WF, Gee JM, Morris J, Nicholson RI, Potten CS, et al. Effect of epidermal growth factor receptor tyrosine kinase inhibition on epithelial proliferation in normal and premalignant breast. Cancer Res. 2002;62(1):122–8.

    PubMed  Google Scholar 

  91. Haddad RI, Shin DM. Recent advances in head and neck cancer. N Engl J Med. 2008;359(11):1143–54.

    PubMed  Google Scholar 

  92. Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003;290(16):2149–58.

    PubMed  Google Scholar 

  93. Stadler WM. Targeted agents for the treatment of advanced renal cell carcinoma. Cancer. 2005;104(11):2323–33.

    PubMed  Google Scholar 

  94. Wong SF. Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. Clin Ther. 2005;27(6):684–94.

    PubMed  Google Scholar 

  95. Gold KA, Lee HY, Kim ES. Targeted therapies in squamous cell carcinoma of the head and neck. Cancer. 2009;115(5):922–35.

    PubMed  Google Scholar 

  96. Adjei AA, Molina JR, Mandrekar SJ, Marks R, Reid JR, Croghan G, et al. Phase I trial of sorafenib in combination with gefitinib in patients with refractory or recurrent non-small cell lung cancer. Clin Cancer Res. 2007;13(9):2684–91.

    PubMed  Google Scholar 

  97. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351(4):337–45.

    PubMed  Google Scholar 

  98. Blick SK, Scott LJ. Cetuximab: a review of its use in squamous cell carcinoma of the head and neck and metastatic colorectal cancer. Drugs. 2007;67(17):2585–607.

    PubMed  Google Scholar 

  99. Tejwani A, Wu S, Jia Y, Agulnik M, Millender L, Lacouture ME. Increased risk of high-grade dermatologic toxicities with radiation plus epidermal growth factor receptor inhibitor therapy. Cancer. 2009;115(6):1286–99.

    PubMed  Google Scholar 

  100. Pryor DI, Porceddu SV, Burmeister BH, Guminski A, Thomson DB, Shepherdson K, et al. Enhanced toxicity with concurrent cetuximab and radiotherapy in head and neck cancer. Radiother Oncol. 2009;90(2):172–6.

    PubMed  Google Scholar 

  101. Belani CP, Schreeder MT, Steis RG, Guidice RA, Marsland TA, Butler EH, et al. Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer: a multicenter phase 2 study. Cancer. 2008;113(9):2512–7.

    PubMed  Google Scholar 

  102. Lenz HJ. Anti-EGFR mechanism of action: antitumor effect and underlying cause of adverse events. Oncology. 2006;20(5 Suppl 2):5–13.

    PubMed  Google Scholar 

  103. Motzer RJ, Amato R, Todd M, Hwu WJ, Cohen R, Baselga J, et al. Phase II trial of antiepidermal growth factor receptor antibody C225 in patients with advanced renal cell carcinoma. Investig New Drugs. 2003;21(1):99–101.

    Google Scholar 

  104. Reynolds NA, Wagstaff AJ. Cetuximab: in the treatment of metastatic colorectal cancer. Drugs. 2004;64(1):109–18.

    PubMed  Google Scholar 

  105. Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 2004;22(7):1201–8.

    PubMed  Google Scholar 

  106. Thomas M. Cetuximab: adverse event profile and recommendations for toxicity management. Clin J Oncol Nurs. 2005;9(3):332–8.

    PubMed  Google Scholar 

  107. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116–27.

    PubMed  Google Scholar 

  108. Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007;25(16):2171–7.

    PubMed  Google Scholar 

  109. Xiong HQ, Rosenberg A, LoBuglio A, Schmidt W, Wolff RA, Deutsch J, et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial. J Clin Oncol. 2004;22(13):2610–6.

    PubMed  Google Scholar 

  110. Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007;25(13):1658–64.

    PubMed  Google Scholar 

  111. Van Cutsem E, Siena S, Humblet Y, Canon JL, Maurel J, Bajetta E, et al. An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy. Ann Oncol. 2008;19(1):92–8.

    PubMed  Google Scholar 

  112. Rowinsky EK, Schwartz GH, Gollob JA, Thompson JA, Vogelzang NJ, Figlin R, et al. Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J Clin Oncol. 2004;22(15):3003–15.

    PubMed  Google Scholar 

  113. Giusti RM, Shastri KA, Cohen MH, Keegan P, Pazdur R. FDA drug approval summary: panitumumab (Vectibix). Oncologist. 2007;12(5):577–83.

    PubMed  Google Scholar 

  114. Muro K, Yoshino T, Doi T, Shirao K, Takiuchi H, Hamamoto Y, et al. A phase 2 clinical trial of panitumumab monotherapy in Japanese patients with metastatic colorectal cancer. Jpn J Clin Oncol. 2009;39(5):321–6.

    PubMed  Google Scholar 

  115. Weiner LM, Belldegrun AS, Crawford J, Tolcher AW, Lockbaum P, Arends RH, et al. Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies. Clin Cancer Res. 2008;14(2):502–8.

    PubMed  Google Scholar 

  116. Kinnings SL, Jackson RM. Binding site similarity analysis for the functional classification of the protein kinase family. J Chem Inf Model. 2009;49(2):318–29.

    PubMed  Google Scholar 

  117. Wang LX, Agulnik M. Promising newer molecular-targeted therapies in head and neck cancer. Drugs. 2008;68(12):1609–19.

    PubMed  Google Scholar 

  118. Laurent-Puig P, Taieb J. Lessons from Tarceva in pancreatic cancer: where are we now, and how should future trials be designed in pancreatic cancer? Curr Opin Oncol. 2008;20(4):454–8.

    PubMed  Google Scholar 

  119. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353(2):123–32.

    PubMed  Google Scholar 

  120. Sandler AB. Nondermatologic adverse events associated with anti-EGFR therapy. Oncology. 2006;20(5 Suppl 2):35–40.

    PubMed  Google Scholar 

  121. Elting LS, Chang YC, Parelkar P, Boers-Doets CB, Michelet M, Hita G, et al. Risk of oral and gastrointestinal mucosal injury among patients receiving selected targeted agents: a meta-analysis. Support Care Cancer. 2013;21(11):3243–54.

    PubMed  Google Scholar 

  122. Sequist LV, Yang JC, Yamamoto N, O’Byrne K, Hirsh V, Mok T, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327–34.

    PubMed  Google Scholar 

  123. Bukowski RM. Systemic therapy for metastatic renal cell carcinoma in treatment naive patients: a risk-based approach. Expert Opin Pharmacother. 2010;11(14):2351–62.

    PubMed  Google Scholar 

  124. Shameem R, Lacouture M, Wu S. Incidence and risk of high-grade stomatitis with mTOR inhibitors in cancer patients. Cancer Investig. 2015;33(3):70–7.

    Google Scholar 

  125. Boers-Doets CB, Raber-Durlacher JE, Treister NS, Epstein JB, Arends AB, Wiersma DR, et al. Mammalian target of rapamycin inhibitor-associated stomatitis. Future Oncol. 2013;9(12):1883–92.

    PubMed  Google Scholar 

  126. Amato RJ, Jac J, Giessinger S, Saxena S, Willis JP. A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer. Cancer. 2009;115(11):2438–46.

    PubMed  Google Scholar 

  127. Wolpin BM, Hezel AF, Abrams T, Blaszkowsky LS, Meyerhardt JA, Chan JA, et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol. 2009;27(2):193–8.

    PubMed  PubMed Central  Google Scholar 

  128. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer. 2010;116(18):4256–65.

    PubMed  Google Scholar 

  129. Porta C, Osanto S, Ravaud A, Climent MA, Vaishampayan U, White DA, et al. Management of adverse events associated with the use of everolimus in patients with advanced renal cell carcinoma. Eur J Cancer. 2011;47(9):1287–98.

    PubMed  Google Scholar 

  130. Raymond E, Alexandre J, Faivre S, Vera K, Materman E, Boni J, et al. Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer. J Clin Oncol. 2004;22(12):2336–47.

    PubMed  Google Scholar 

  131. Gridelli C, Maione P, Rossi A. The potential role of mTOR inhibitors in non-small cell lung cancer. Oncologist. 2008;13(2):139–47.

    PubMed  Google Scholar 

  132. Bellmunt J, Szczylik C, Feingold J, Strahs A, Berkenblit A. Temsirolimus safety profile and management of toxic effects in patients with advanced renal cell carcinoma and poor prognostic features. Ann Oncol. 2008;19(8):1387–92.

    PubMed  Google Scholar 

  133. Kwitkowski VE, Prowell TM, Ibrahim A, Farrell AT, Justice R, Mitchell SS, et al. FDA approval summary: temsirolimus as treatment for advanced renal cell carcinoma. Oncologist. 2010;15(4):428–35.

    PubMed  PubMed Central  Google Scholar 

  134. Mita MM, Mita AC, Chu QS, Rowinsky EK, Fetterly GJ, Goldston M, et al. Phase I trial of the novel mammalian target of rapamycin inhibitor deforolimus (AP23573; MK-8669) administered intravenously daily for 5 days every 2 weeks to patients with advanced malignancies. J Clin Oncol. 2008;26(3):361–7.

    PubMed  Google Scholar 

  135. 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(11):1026–33.

    PubMed  Google Scholar 

  136. Kennedy JA, Hobbs G. Tyrosine kinase inhibitors in the treatment of chronic-phase CML: strategies for frontline decision-making. Curr Hematol Malig Rep. 2018;13(3):202–11.

    PubMed  PubMed Central  Google Scholar 

  137. Watson GA, Kelly D, Melland-Smith M, Gleeson J, McEntee G, Kelly CM, et al. Get the GIST? An overview of gastrointestinal stromal tumours. Ir J Med Sci. 2016;185(2):319–26.

    PubMed  Google Scholar 

  138. Ryu MH, Kang WK, Bang YJ, Lee KH, Shin DB, Ryoo BY, et al. A prospective, multicenter, phase 2 study of imatinib mesylate in Korean patients with metastatic or unresectable gastrointestinal stromal tumor. Oncology. 2009;76(5):326–32.

    PubMed  Google Scholar 

  139. Kloos RT, Ringel MD, Knopp MV, Hall NC, King M, Stevens R, et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol. 2009;27(10):1675–84.

    PubMed  PubMed Central  Google Scholar 

  140. da Motta Girardi D, Correa TS, Crosara Teixeira M, Dos Santos Fernandes G. Hepatocellular carcinoma: review of targeted and immune therapies. J Gastrointest Cancer. 2018;28(10):018–0121.

    Google Scholar 

  141. Coppin C, Kollmannsberger C, Le L, Porzsolt F, Wilt TJ. Targeted therapy for advanced renal cell cancer (RCC): a Cochrane systematic review of published randomised trials. BJU Int. 2011;108(10):1556–63.

    PubMed  Google Scholar 

  142. Chi KN, Ellard SL, Hotte SJ, Czaykowski P, Moore M, Ruether JD, et al. A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer. Ann Oncol. 2008;19(4):746–51.

    PubMed  Google Scholar 

  143. Duran I, Hotte SJ, Hirte H, Chen EX, MacLean M, Turner S, et al. Phase I targeted combination trial of sorafenib and erlotinib in patients with advanced solid tumors. Clin Cancer Res. 2007;13(16):4849–57.

    PubMed  Google Scholar 

  144. Eisen T, Ahmad T, Flaherty KT, Gore M, Kaye S, Marais R, et al. Sorafenib in advanced melanoma: a phase II randomised discontinuation trial analysis. Br J Cancer. 2006;95(5):581–6.

    PubMed  PubMed Central  Google Scholar 

  145. Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(8):1280–9.

    PubMed  Google Scholar 

  146. Herrmann E, Bierer S, Gerss J, Kopke T, Hertle L, Wulfing C. Prospective comparison of sorafenib and sunitinib for second-line treatment of cytokine-refractory kidney cancer patients. Oncology. 2008;74(3–4):216–22.

    PubMed  Google Scholar 

  147. Mross K, Steinbild S, Baas F, Gmehling D, Radtke M, Voliotis D, et al. Results from an in vitro and a clinical/pharmacological phase I study with the combination irinotecan and sorafenib. Eur J Cancer. 2007;43(1):55–63.

    PubMed  Google Scholar 

  148. Richly H, Henning BF, Kupsch P, Passarge K, Grubert M, Hilger RA, et al. Results of a phase I trial of sorafenib (BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors. Ann Oncol. 2006;17(5):866–73.

    PubMed  Google Scholar 

  149. Siu LL, Awada A, Takimoto CH, Piccart M, Schwartz B, Giannaris T, et al. Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer. Clin Cancer Res. 2006;12(1):144–51.

    PubMed  Google Scholar 

  150. Lee WJ, Lee JL, Chang SE, Lee MW, Kang YK, Choi JH, et al. Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. Br J Dermatol. 2009;161(5):1045–51.

    PubMed  Google Scholar 

  151. Awada A, Hendlisz A, Gil T, Bartholomeus S, Mano M, de Valeriola D, et al. Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer. 2005;92(10):1855–61.

    PubMed  PubMed Central  Google Scholar 

  152. Procopio G, Verzoni E, Gevorgyan A, Mancin M, Pusceddu S, Catena L, et al. Safety and activity of sorafenib in different histotypes of advanced renal cell carcinoma. Oncology. 2007;73(3–4):204–9.

    PubMed  Google Scholar 

  153. Riechelmann RP, Chin S, Wang L, Tannock IF, Berthold DR, Moore MJ, et al. Sorafenib for metastatic renal cancer: the Princess Margaret experience. Am J Clin Oncol. 2008;31(2):182–7.

    PubMed  Google Scholar 

  154. Strumberg D, Clark JW, Awada A, Moore MJ, Richly H, Hendlisz A, et al. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist. 2007;12(4):426–37.

    PubMed  Google Scholar 

  155. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.

    PubMed  Google Scholar 

  156. George S, Blay JY, Casali PG, Le Cesne A, Stephenson P, Deprimo SE, et al. Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur J Cancer. 2009;45(11):1959–68.

    PubMed  Google Scholar 

  157. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115–24.

    PubMed  Google Scholar 

  158. Uemura H, Shinohara N, Yuasa T, Tomita Y, Fujimoto H, Niwakawa M, et al. A phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma: insights into the treatment, efficacy and safety. Jpn J Clin Oncol. 2010;40(3):194–202.

    PubMed  Google Scholar 

  159. Adams VR, Leggas M. Sunitinib malate for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Clin Ther. 2007;29(7):1338–53.

    PubMed  Google Scholar 

  160. Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004;3(5):391–400.

    PubMed  Google Scholar 

  161. Herbst RS, Sandler A. Bevacizumab and erlotinib: a promising new approach to the treatment of advanced NSCLC. Oncologist. 2008;13(11):1166–76.

    PubMed  Google Scholar 

  162. Agulnik M, Cohen EW, Cohen RB, Chen EX, Vokes EE, Hotte SJ, et al. Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non adenoid cystic carcinoma malignant tumors of the salivary glands. J Clin Oncol. 2007;25(25):3978–84.

    PubMed  Google Scholar 

  163. Chu QS, Cianfrocca ME, Goldstein LJ, Gale M, Murray N, Loftiss J, et al. A phase I and pharmacokinetic study of lapatinib in combination with letrozole in patients with advanced cancer. Clin Cancer Res. 2008;14(14):4484–90.

    PubMed  Google Scholar 

  164. Nakagawa K, Minami H, Kanezaki M, Mukaiyama A, Minamide Y, Uejima H, et al. Phase I dose-escalation and pharmacokinetic trial of lapatinib (GW572016), a selective oral dual inhibitor of ErbB-1 and -2 tyrosine kinases, in Japanese patients with solid tumors. Jpn J Clin Oncol. 2009;39(2):116–23.

    PubMed  Google Scholar 

  165. Sonis ST, Sonis AL, Lieberman A. Oral complications in patients receiving treatment for malignancies other than of the head and neck. J Am Dent Assoc. 1978;97(3):468–72.

    PubMed  Google Scholar 

  166. 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(6):484–90.

    PubMed  Google Scholar 

  167. Zalcberg J, Kerr D, Seymour L, Palmer M. Haematological and non-haematological toxicity after 5-fluorouracil and leucovorin in patients with advanced colorectal cancer is significantly associated with gender, increasing age and cycle number. Tomudex International Study Group. Eur J Cancer. 1998;34(12):1871–5.

    PubMed  Google Scholar 

  168. Berger AM, Eilers J. Factors influencing oral cavity status during high-dose antineoplastic therapy: a secondary data analysis. Oncol Nurs Forum. 1998;25(9):1623–6.

    PubMed  Google Scholar 

  169. Eilers J, Million R. Prevention and management of oral mucositis in patients with cancer. Semin Oncol Nurs. 2007;23(3):201–12.

    PubMed  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  171. Chansky K, Benedetti J, Macdonald JS. Differences in toxicity between men and women treated with 5-fluorouracil therapy for colorectal carcinoma. Cancer. 2005;103(6):1165–71.

    PubMed  Google Scholar 

  172. Sloan JA, Goldberg RM, Sargent DJ, Vargas-Chanes D, Nair S, Cha SS, et al. Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol. 2002;20(6):1491–8.

    PubMed  Google Scholar 

  173. Raber-Durlacher JE. Current practices for management of oral mucositis in cancer patients. Support Care Cancer. 1999;7(2):71–4.

    PubMed  Google Scholar 

  174. Chen SC, Lai YH, Huang BS, Lin CY, Fan KH, Chang JT. Changes and predictors of radiation-induced oral mucositis in patients with oral cavity cancer during active treatment. Eur J Oncol Nurs. 2015;19(3):214–9.

    PubMed  Google Scholar 

  175. 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.

    PubMed  Google Scholar 

  176. Luo DH, Hong MH, Guo L, Cao KJ, Deng MQ, Mo HY. Analysis of oral mucositis risk factors during radiotherapy for nasopharyngeal carcinoma patients and establishment of a discriminant model. Ai Zheng. 2005;24(7):850–4.

    PubMed  Google Scholar 

  177. Patussi C, Sassi LM, Munhoz EC, Zanicotti RT, Schussel JL. Clinical assessment of oral mucositis and candidiasis compare to chemotherapic nadir in transplanted patients. Braz Oral Res. 2014;28:1–7.

    PubMed  Google Scholar 

  178. Robien K, Schubert MM, Bruemmer B, Lloid ME, Potter JD, Ulrich CM. Predictors of oral mucositis in patients receiving hematopoietic cell transplants for chronic myelogenous leukemia. J Clin Oncol. 2004;22(7):1268–75.

    PubMed  Google Scholar 

  179. Evans WE, McLeod HL. Pharmacogenomics—drug disposition, drug targets, and side effects. N Engl J Med. 2003;348(6):538–49.

    PubMed  Google Scholar 

  180. Robien K, Schubert MM, Chay T, Bigler J, Storb R, Yasui Y, et al. Methylenetetrahydrofolate reductase and thymidylate synthase genotypes modify oral mucositis severity following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2006;37(8):799–800. https://doi.org/10.1038/sj.bmt.1705330.

    CrossRef  PubMed  Google Scholar 

  181. Salavaggione OE, Wang L, Wiepert M, Yee VC, Weinshilboum RM. Thiopurine S-methyltransferase pharmacogenetics: variant allele functional and comparative genomics. Pharmacogenet Genomics. 2005;15(11):801–15.

    PubMed  Google Scholar 

  182. Bogunia-Kubik K, Polak M, Lange A. TNF polymorphisms are associated with toxic but not with aGVHD complications in the recipients of allogeneic sibling haematopoietic stem cell transplantation. Bone Marrow Transplant. 2003;32(6):617–22.

    PubMed  Google Scholar 

  183. Hahn T, Zhelnova E, Sucheston L, Demidova I, Savchenko V, Battiwalla M, et al. A deletion polymorphism in glutathione-S-transferase mu (GSTM1) and/or theta (GSTT1) is associated with an increased risk of toxicity after autologous blood and marrow transplantation. Biol Blood Marrow Transplant. 2010;16(6):801–8.

    PubMed  Google Scholar 

  184. 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;28:5059–73. https://doi.org/10.1007/s00520-020-05579-7.

  185. Ostman A, Augsten M. Cancer-associated fibroblasts and tumor growth—bystanders turning into key players. Curr Opin Genet Dev. 2009;19(1):67–73.

    PubMed  Google Scholar 

  186. Pries R, Wollenberg B. Cytokines in head and neck cancer. Cytokine Growth Factor Rev. 2006;17(3):141–6.

    PubMed  Google Scholar 

  187. Bondi E, Baroni C, Prete A, Gatti M, Carrassi A, Lodi G, et al. Local antimicrobial therapy of oral mucositis in paediatric patients undergoing bone marrow transplantation. Oral Oncol. 1997;33(5):322–6.

    PubMed  Google Scholar 

  188. 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(6):921–7.

    PubMed  Google Scholar 

  189. Epstein JB, Vickars L, Spinelli J, Reece D. Efficacy of chlorhexidine and nystatin rinses in prevention of oral complications in leukemia and bone marrow transplantation. Oral Surg Oral Med Oral Pathol. 1992;73(6):682–9.

    PubMed  Google Scholar 

  190. 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(3):331–8.

    PubMed  Google Scholar 

  191. 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(12):2630–3.

    PubMed  Google Scholar 

  192. Loury D, Embree JR, Steinberg DA, Sonis ST, Fiddes JC. Effect of local application of the antimicrobial peptide IB-367 on the incidence and severity of oral mucositis in hamsters. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87(5):544–51.

    PubMed  Google Scholar 

  193. 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(2):154–61.

    PubMed  Google Scholar 

  194. Wahlin YB. Effects of chlorhexidine mouthrinse on oral health in patients with acute leukemia. Oral Surg Oral Med Oral Pathol. 1989;68(3):279–87.

    PubMed  Google Scholar 

  195. Bodey GP, Rodriguez V, Chang HY, Narboni. Fever and infection in leukemic patients: a study of 494 consecutive patients. Cancer. 1978;41(4):1610–22.

    PubMed  Google Scholar 

  196. El-Sayed S, Nabid A, Shelley W, Hay J, Balogh J, Gelinas M, 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(19):3956–63.

    PubMed  Google Scholar 

  197. Rand KH, Kramer B, Johnson AC. Cancer chemotherapy associated symptomatic stomatitis: role of herpes simplex virus (HSV). Cancer. 1982;50(7):1262–5.

    PubMed  Google Scholar 

  198. Djuric M, Jankovic L, Jovanovic T, Pavlica D, Brkic S, Knezevic A, et al. Prevalence of oral herpes simplex virus reactivation in cancer patients: a comparison of different techniques of viral detection. J Oral Pathol Med. 2009;38(2):167–73.

    PubMed  Google Scholar 

  199. Woo SB, Sonis ST, Sonis AL. The role of herpes simplex virus in the development of oral mucositis in bone marrow transplant recipients. Cancer. 1990;66(11):2375–9.

    PubMed  Google Scholar 

  200. Feld R. The role of surveillance cultures in patients likely to develop chemotherapy-induced mucositis. Support Care Cancer. 1997;5(5):371–5.

    PubMed  Google Scholar 

  201. Lockhart PB, Brennan MT, Kent ML, Packman CH, Norton HJ, Fox PC, 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(7):713–20.

    PubMed  Google Scholar 

  202. Scarantino C, LeVeque F, Swann RS, White R, Schulsinger A, Hodson DI, 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(5):252–8.

    PubMed  Google Scholar 

  203. Sonis ST. A biological approach to mucositis. J Support Oncol. 2004;2(1):21–32.

    PubMed  Google Scholar 

  204. Sonis ST. Pathobiology of mucositis. Semin Oncol Nurs. 2004;20(1):11–5.

    PubMed  Google Scholar 

  205. Song SJ, Han K, Lee SS, Park JB. Association between the number of natural teeth and diabetic retinopathy among type 2 diabetes mellitus: the Korea national health and nutrition examination survey. Medicine. 2017;96(47):0000000000008694.

    Google Scholar 

  206. Elad S, Yarom N, Zadik Y, Kuten-Shorrer M, Sonis ST. The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies. CA Cancer J Clin. 2021;29. https://doi.org/10.3322/caac.21704. Online ahead of print. PMID: 34714553.

  207. Kojima I, Sakamoto M, Iikubo M, Kumamoto H, Muroi A, Sugawara Y, et al. Diagnostic performance of MR imaging of three major salivary glands for Sjogren’s syndrome. Oral Dis. 2017;23(1):84–90.

    PubMed  Google Scholar 

  208. Eslamipour F, Borzabadi-Farahani A, Asgari I. The relationship between aging and oral health inequalities assessed by the DMFT index. Eur J Paediatr Dent. 2010;11(4):193–9.

    PubMed  Google Scholar 

  209. Zimmermann H, Hagenfeld D, Diercke K, El-Sayed N, Fricke J, Greiser KH, et al. Pocket depth and bleeding on probing and their associations with dental, lifestyle, socioeconomic and blood variables: a cross-sectional, multicenter feasibility study of the German National Cohort. BMC Oral Health. 2015;15(7):1472–6831.

    Google Scholar 

  210. Sonis ST. The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med. 2002;13(5):380–9.

    PubMed  Google Scholar 

  211. Lee HK, Lee KD, Merchant AT, Lee SK, Song KB, Lee SG, et al. More missing teeth are associated with poorer general health in the rural Korean elderly. Arch Gerontol Geriatr. 2010;50(1):30–3.

    PubMed  Google Scholar 

  212. Aoyama N, Suzuki JI, Kobayashi N, Hanatani T, Ashigaki N, Yoshida A, et al. Japanese cardiovascular disease patients with diabetes mellitus suffer increased tooth loss in comparison to those without diabetes mellitus—a cross-sectional study. Intern Med. 2018;57(6):777–82.

    PubMed  Google Scholar 

  213. Nakamura T, Oshiumi Y, Yonetsu K, Muranaka T, Sakai K, Kanda S. Salivary SPECT and factor analysis in Sjogren’s syndrome. Acta Radiol. 1991;32(5):406–10.

    PubMed  Google Scholar 

  214. Pimentel EL, Azevedo VM, Castro Rde A, Reis LC, De Lorenzo A. Caries experience in young children with congenital heart disease in a developing country. Braz Oral Res. 2013;27(2):103–8.

    PubMed  Google Scholar 

  215. Berger K, Schopohl D, Bollig A, Strobach D, Rieger C, Rublee D, et al. Burden of oral mucositis: a systematic review and implications for future research. Oncol Res Treat. 2018;41(6):399–405.

    PubMed  Google Scholar 

  216. Sikka M, Sequeira PS, Acharya S, Bhat M, Rao A, Nagaraj A. Poor oral health in patients with coronary heart disease: a case-control study of Indian adults. N Z Med J. 2011;124(1347):53–62.

    PubMed  Google Scholar 

  217. Shin HS. Association between the number of teeth and hypertension in a study based on 13,561 participants. J Periodontol. 2018;89(4):397–406.

    PubMed  Google Scholar 

  218. Musskopf ML, Daudt LD, Weidlich P, Gerchman F, Gross JL, Oppermann RV. Metabolic syndrome as a risk indicator for periodontal disease and tooth loss. Clin Oral Investig. 2017;21(2):675–83.

    PubMed  Google Scholar 

  219. Sharda AJ, Shetty S. Relationship of periodontal status and dental caries status with oral health knowledge, attitude and behavior among professional students in India. Int J Oral Sci. 2009;1(4):196–206.

    PubMed  PubMed Central  Google Scholar 

  220. Shin HS. The number of teeth is inversely associated with metabolic syndrome: a Korean nationwide population-based study. J Periodontol. 2017;88(9):830–8.

    PubMed  Google Scholar 

  221. Cao X, Wang D, Zhou J, Yuan H, Chen Z. Relationship between dental caries and metabolic syndrome among 13,998 middle-aged urban Chinese. J Diabetes. 2017;9(4):378–85.

    PubMed  Google Scholar 

  222. Tonami H, Ogawa Y, Matoba M, Kuginuki Y, Yokota H, Higashi K, et al. MR sialography in patients with Sjogren syndrome. AJNR Am J Neuroradiol. 1998;19(7):1199–203.

    PubMed  PubMed Central  Google Scholar 

  223. de Clerck LS, Corthouts R, Francx L, Brussaard C, de Schepper A, Vercruysse HA, et al. Ultrasonography and computer tomography of the salivary glands in the evaluation of Sjogren’s syndrome. Comparison with parotid sialography. J Rheumatol. 1988;15(12):1777–81.

    PubMed  Google Scholar 

  224. Eke PI, Dye BA, Wei L, Slade GD, Thornton-Evans GO, Borgnakke WS, et al. Update on prevalence of periodontitis in adults in the United States: NHANES 2009 to 2012. J Periodontol. 2015;86(5):611–22.

    PubMed  PubMed Central  Google Scholar 

  225. DeStefano F, Anda RF, Kahn HS, Williamson DF, Russell CM. Dental disease and risk of coronary heart disease and mortality. BMJ. 1993;306(6879):688–91.

    PubMed  PubMed Central  Google Scholar 

  226. Najafipour H, Malek Mohammadi T, Rahim F, Haghdoost AA, Shadkam M, Afshari M. Association of oral health and cardiovascular disease risk factors “results from a community based study on 5900 adult subjects”. ISRN Cardiol. 2013;9:782126.

    Google Scholar 

  227. Jadu FM, Hill ML, Yaffe MJ, Lam EW. Optimization of exposure parameters for cone beam computed tomography sialography. Dentomaxillofac Radiol. 2011;40(6):362–8.

    PubMed  PubMed Central  Google Scholar 

  228. Joshipura KJ, Rimm EB, Douglass CW, Trichopoulos D, Ascherio A, Willett WC. Poor oral health and coronary heart disease. J Dent Res. 1996;75(9):1631–6.

    PubMed  Google Scholar 

  229. Song GG, Lee YH. Diagnostic accuracies of sialography and salivary ultrasonography in Sjogren’s syndrome patients: a meta-analysis. Clin Exp Rheumatol. 2014;32(4):516–22.

    PubMed  Google Scholar 

  230. Ali HM, Mustafa M, Hasabalrasol S, Elshazali OH, Nasir EF, Ali RW, et al. Presence of plaque, gingivitis and caries in Sudanese children with congenital heart defects. Clin Oral Investig. 2017;21(4):1299–307.

    PubMed  Google Scholar 

  231. Bernabe E, Sheiham A. Age, period and cohort trends in caries of permanent teeth in four developed countries. Am J Public Health. 2014;104(7):15.

    Google Scholar 

  232. Franco E, Saunders CP, Roberts GJ, Suwanprasit A. Dental disease, caries related microflora and salivary IgA of children with severe congenital cardiac disease: an epidemiological and oral microbial survey. Pediatr Dent. 1996;18(3):228–35.

    PubMed  Google Scholar 

  233. Delgado-Perez VJ, De La Rosa-Santillana R, Marquez-Corona ML, Avila-Burgos L, Islas-Granillo H, Minaya-Sanchez M, et al. Diabetes or hypertension as risk indicators for missing teeth experience: an exploratory study in a sample of Mexican adults. Niger J Clin Pract. 2017;20(10):1335–41.

    PubMed  Google Scholar 

  234. Jansson L, Lavstedt S, Frithiof L, Theobald H. Relationship between oral health and mortality in cardiovascular diseases. J Clin Periodontol. 2001;28(8):762–8.

    PubMed  Google Scholar 

  235. Peterson DE. Research advances in oral mucositis. Curr Opin Oncol. 1999;11(4):261–6.

    PubMed  Google Scholar 

  236. Sonis ST. Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol. 1998;34(1):39–43.

    PubMed  Google Scholar 

  237. Blijlevens N, Schwenkglenks M, Bacon P, D’Addio A, Einsele H, Maertens J, 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(9):1519–25.

    PubMed  Google Scholar 

  238. Elad S, Zadik Y. Chronic oral mucositis after radiotherapy to the head and neck: a new insight. Support Care Cancer. 2016;24(11):4825–30.

    PubMed  Google Scholar 

  239. Lalla RV, Treister N, Sollecito T, Schmidt B, Patton LL, Mohammadi K, et al. Oral complications at 6 months after radiation therapy for head and neck cancer. Oral Dis. 2017;23(8):1134–43.

    PubMed  PubMed Central  Google Scholar 

  240. McGuire DB, Yeager KA, Dudley WN, Peterson DE, Owen DC, Lin LS, et al. Acute oral pain and mucositis in bone marrow transplant and leukemia patients: data from a pilot study. Cancer Nurs. 1998;21(6):385–93.

    PubMed  Google Scholar 

  241. Chapko MK, Syrjala KL, Schilter L, Cummings C, Sullivan KM. Chemoradiotherapy toxicity during bone marrow transplantation: time course and variation in pain and nausea. Bone Marrow Transplant. 1989;4(2):181–6.

    PubMed  Google Scholar 

  242. Miaskowski C. Biology of mucosal pain. J Natl Cancer Inst Monogr. 2001;29:37–40.

    Google Scholar 

  243. Harris DJ, Eilers J, Harriman A, Cashavelly BJ, Maxwell C. Putting evidence into practice: evidence-based interventions for the management of oral mucositis. Clin J Oncol Nurs. 2008;12(1):141–52.

    PubMed  Google Scholar 

  244. Lalla RV, Sonis ST, Peterson DE. Management of oral mucositis in patients who have cancer. Dent Clin N Am. 2008;52(1):61–77.

    PubMed  Google Scholar 

  245. 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(1):210–5.

    PubMed  Google Scholar 

  246. de Oliveira MA, Martins EMF, Wang Q, Sonis S, Demetri G, George S, et al. Clinical presentation and management of mTOR inhibitor-associated stomatitis. Oral Oncol. 2011;47(10):998–1003.

    PubMed  Google Scholar 

  247. Martins F, de Oliveira MA, Wang Q, Sonis S, Gallottini M, George S, et al. A review of oral toxicity associated with mTOR inhibitor therapy in cancer patients. Oral Oncol. 2013;49(4):293–8.

    PubMed  Google Scholar 

  248. Yuan R, Kay A, Berg WJ, Lebwohl D. Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. J Hematol Oncol. 2009;2(45):1756–8722.

    Google Scholar 

  249. Pavel ME, Hainsworth JD, Baudin E, Peeters M, Horsch D, Winkler RE, et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011;378(9808):2005–12.

    PubMed  Google Scholar 

  250. Lacouture ME, Maitland ML, Segaert S, Setser A, Baran R, Fox LP, et al. A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer. 2010;18(4):509–22.

    PubMed  Google Scholar 

  251. Sonis ST, Oster G, Fuchs H, Bellm L, Bradford WZ, Edelsberg J, et al. Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol. 2001;19(8):2201–5.

    PubMed  Google Scholar 

  252. Cohen J, Donnelly JP, Worsley AM, Catovsky D, Goldman JM, Galton DA. Septicaemia caused by viridans streptococci in neutropenic patients with leukaemia. Lancet. 1983;2(8365–66):1452–4.

    PubMed  Google Scholar 

  253. Elting LS, Bodey GP, Keefe BH. Septicemia and shock syndrome due to viridans streptococci: a case-control study of predisposing factors. Clin Infect Dis. 1992;14(6):1201–7.

    PubMed  Google Scholar 

  254. Wingard JR, Niehaus CS, Peterson DE, Jones RJ, Piantadosi S, Levin LS, et al. Oral mucositis after bone marrow transplantation. A marker of treatment toxicity and predictor of hepatic veno-occlusive disease. Oral Surg Oral Med Oral Pathol. 1991;72(4):419–24.

    PubMed  Google Scholar 

  255. 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(4):1110–20.

    PubMed  Google Scholar 

  256. Elting LS, Keefe DM, Sonis ST, Garden AS, Spijkervet FK, Barasch A, et al. Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life. Cancer. 2008;113(10):2704–13.

    PubMed  Google Scholar 

  257. Parulekar W, Mackenzie R, Bjarnason G, Jordan RC. Scoring oral mucositis. Oral Oncol. 1998;34(1):63–71.

    PubMed  Google Scholar 

  258. Squier CA. Oral complications of cancer therapies. Mucosal alterations. NCI Monogr. 1990;9:169–72.

    Google Scholar 

  259. Epstein JB, Beaumont JL, Gwede CK, Murphy B, Garden AS, Meredith R, et al. Longitudinal evaluation of the oral mucositis weekly questionnaire-head and neck cancer, a patient-reported outcomes questionnaire. Cancer. 2007;109(9):1914–22.

    PubMed  Google Scholar 

  260. World Health Organization. WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization; 1979.

    Google Scholar 

  261. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf.

  262. 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(5):1341–6. https://doi.org/10.1016/0360-3016(95)00060-C.

    CrossRef  PubMed  Google Scholar 

  263. McGuire DB, Peterson DE, Muller S, Owen DC, Slemmons MF, Schubert MM. The 20 item oral mucositis index: reliability and validity in bone marrow and stem cell transplant patients. Cancer Investig. 2002;20(7–8):893–903.

    Google Scholar 

  264. Schubert MM, Williams BE, Lloid ME, Donaldson G, Chapko MK. Clinical assessment scale for the rating of oral mucosal changes associated with bone marrow transplantation. Development of an oral mucositis index. Cancer. 1992;69(10):2469–77.

    PubMed  Google Scholar 

  265. Sonis ST, Eilers JP, Epstein JB, LeVeque FG, Liggett WH Jr, 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. Mucositis Study Group. Cancer. 1999;85(10):2103–13.

    PubMed  Google Scholar 

  266. Development of a staging system for chemotherapy-induced stomatitis. Western Consortium for Cancer Nursing Research. Cancer Nurs. 1991;14(1):6–12.

    Google Scholar 

  267. List MA, Ritter-Sterr C, Lansky SB. A performance status scale for head and neck cancer patients. Cancer. 1990;66(3):564–9.

    PubMed  Google Scholar 

  268. List MA, Ritter-Sterr CA, Baker TM, Colangelo LA, Matz G, Pauloski BR, et al. Longitudinal assessment of quality of life in laryngeal cancer patients. Head Neck. 1996;18(1):1–10.

    PubMed  Google Scholar 

  269. List MA, Mumby P, Haraf D, Siston A, Mick R, MacCracken E, et al. Performance and quality of life outcome in patients completing concomitant chemoradiotherapy protocols for head and neck cancer. Qual Life Res. 1997;6(3):274–84.

    PubMed  Google Scholar 

  270. List MA, Siston A, Haraf D, Schumm P, Kies M, Stenson K, et al. Quality of life and performance in advanced head and neck cancer patients on concomitant chemoradiotherapy: a prospective examination. J Clin Oncol. 1999;17(3):1020–8.

    PubMed  Google Scholar 

  271. Eilers J, Berger AM, Petersen MC. Development, testing, and application of the oral assessment guide. Oncol Nurs Forum. 1988;15(3):325–30.

    PubMed  Google Scholar 

  272. Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Investig New Drugs. 1992;10(4):239–53.

    Google Scholar 

  273. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649–55.

    PubMed  Google Scholar 

  274. Spijkervet FK, van Saene HK, Panders AK, Vermey A, Mehta DM. Scoring irradiation mucositis in head and neck cancer patients. J Oral Pathol Med. 1989;18(3):167–71.

    PubMed  Google Scholar 

  275. Walsh LJ, Hill G, Seymour G, Roberts A. A scoring system for the quantitative evaluation of oral mucositis during bone marrow transplantation. Spec Care Dentist. 1990;10(6):190–5.

    PubMed  Google Scholar 

  276. Tardieu C, Cowen D, Thirion X, Franquin JC. Quantitative scale of oral mucositis associated with autologous bone marrow transplantation. Eur J Cancer B Oral Oncol. 1996;6:381–7.

    Google Scholar 

  277. Donnelly JP, Muus P, Schattenberg A, De Witte T, Horrevorts A, DePauw BE. A scheme for daily monitoring of oral mucositis in allogeneic BMT recipients. Bone Marrow Transplant. 1992;9(6):409–13.

    PubMed  Google Scholar 

  278. Dibble SL, Shiba G, MacPhail L, Dodd MJ. MacDibbs Mouth Assessment. A new tool to evaluate mucositis in the radiation therapy patient. Cancer Pract. 1996;4(3):135–40.

    PubMed  Google Scholar 

  279. Stiff PJ, Emmanouilides C, Bensinger WI, Gentile T, Blazar B, Shea TC, et al. Palifermin reduces patient-reported mouth and throat soreness and improves patient functioning in the hematopoietic stem-cell transplantation setting. J Clin Oncol. 2006;24(33):5186–93.

    PubMed  Google Scholar 

  280. List MA, D’Antonio LL, Cella DF, Siston A, Mumby P, Haraf D, 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(11):2294–301.

    PubMed  Google Scholar 

  281. Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol. 1993;11(3):570–9.

    PubMed  Google Scholar 

  282. Cella D, Paul D, Yount S, Winn R, Chang CH, Banik D, et al. What are the most important symptom targets when treating advanced cancer? A survey of providers in the National Comprehensive Cancer Network (NCCN). Cancer Investig. 2003;21(4):526–35.

    Google Scholar 

  283. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365–76.

    PubMed  Google Scholar 

  284. Duncan GG, Epstein JB, Tu D, El Sayed S, Bezjak A, Ottaway J, et al. Quality of life, mucositis, and xerostomia from radiotherapy for head and neck cancers: a report from the NCIC CTG HN2 randomized trial of an antimicrobial lozenge to prevent mucositis. Head Neck. 2005;27(5):421–8.

    PubMed  Google Scholar 

  285. Kyriaki M, Eleni T, Efi P, Ourania K, Vassilios S, Lambros V. The EORTC core quality of life questionnaire (QLQ-C30, version 3.0) in terminally ill cancer patients under palliative care: validity and reliability in a Hellenic sample. Int J Cancer. 2001;94(1):135–9.

    PubMed  Google Scholar 

  286. Bjordal K, Hammerlid E, Ahlner-Elmqvist M, de Graeff A, Boysen M, Evensen JF, et al. Quality of life in head and neck cancer patients: validation of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-H&N35. J Clin Oncol. 1999;17(3):1008–19.

    PubMed  Google Scholar 

  287. Ranna V, Cheng KKF, Castillo DA, Porcello L, Vaddi A, Lalla RV, et al. Development of the MASCC/ISOO clinical practice guidelines for mucositis: an overview of the methods. Support Care Cancer. 2019;27(10):3933–48.

    PubMed  Google Scholar 

  288. 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(10):3969–83.

    PubMed  Google Scholar 

  289. 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):3985–95.

    PubMed  Google Scholar 

  290. 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):3949–67.

    PubMed  Google Scholar 

  291. Bowen JM, Gibson RJ, Coller JK, Blijlevens N, Bossi P, Al-Dasooqi N, et al. Systematic review of agents for the management of cancer treatment-related gastrointestinal mucositis and clinical practice guidelines. Support Care Cancer. 2019;27(10):4011–22.

    PubMed  Google Scholar 

  292. 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. 2020;28(5):2449–56.

    PubMed  Google Scholar 

  293. 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;28(5):2473–84.

    PubMed  Google Scholar 

  294. 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 2: Honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. Support Care Cancer. 2020;28(5):2457–72.

    PubMed  Google Scholar 

  295. Logan RM, Al-Azri AR, Bossi P, Stringer AM, Joy JK, Soga Y, 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(5):2485–98.

    PubMed  Google Scholar 

  296. Elad S, Cheng KKF, Lalla RV, Yarom N, Hong C, Logan RM, Bowen J, Gibson R, Saunders DP, Zadik Y, Ariyawardana A, Correa ME, Ranna V, Bossi P; MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Mucositis guidelines leadership group of the multinational association of supportive care in cancer and international society of oral oncology (MASCC/ISOO). Cancer. 2020;126(19):4423–4431. https://doi.org/10.1002/cncr.33100. Epub 2020 Jul 28. PMID: 32786044.

  297. Peterson DE, O’Shaughnessy JA, Rugo HS, Elad S, Schubert MM, Viet CT, 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(8):1897–907.

    PubMed  PubMed Central  Google Scholar 

  298. De Masson A, Fouchard N, Mery-Bossard L, Dauendorffer JN. Cutaneous and mucosal aphthosis during temsirolimus therapy for advanced renal cell carcinoma: review of cutaneous and mucosal side effects of mTOR inhibitors. Dermatology. 2011;223(1):4–8.

    PubMed  Google Scholar 

  299. Busemann C, Wilfert H, Neumann T, Kiefer T, Dolken G, Kruger WH. Mucositis after reduced intensity conditioning and allogeneic stem cell transplantation. Onkologie. 2011;34(10):518–24.

    PubMed  Google Scholar 

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Abdalla-Aslan, R., Wardill, H., Elad, S. (2022). Oral Mucositis. In: Nair, R. (eds) Orofacial Supportive Care in Cancer . Springer, Cham. https://doi.org/10.1007/978-3-030-86510-8_5

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