Elsevier

Oral Oncology

Volume 46, Issue 6, June 2010, Pages 452-456
Oral Oncology

Review
Oral mucositis

https://doi.org/10.1016/j.oraloncology.2010.03.012Get rights and content

Summary

Mucosal damage is one of the most common adverse effects of radiotherapy and of cytotoxic therapy for cancer. With prevalence between 10% and 100%, depending of the cytotoxic regimen and patient-associated variables, this morbid condition represents a significant problem in oncology. In this paper we address oral mucositis and discuss its pathobiology, risk factors, impact and management in view of the most recent evidence. Despite of clear progress and the development of clinical guidelines, what we currently have to offer to patients to manage mucositis and oropharyngeal pain is still inadequate. Expansion of the knowledge of the pathogenesis of mucositis as well as a better insight into individual risk factors will provide opportunities to improve management strategies.

Introduction

By virtue of their rapid mitotic rate, mucosal cells are natural targets of cancer cytotoxic regimens. This collateral damage affects treatment delivery and is often a dose-limiting toxicity, particularly for (chemo)radiation for head and neck cancers, and conditioning regimens for haematopoietic stem cell transplantation (HSCT). Newer targeted agents such as cetuximab may enhance toxicity of radiotherapy.1 Similarly, rapamycin (mTOR) inhibitors have been reported to cause mouth ulcers.[2], [3] Thus, while other toxicities may be declining, mucosal damage remains an area of concern.

Oral mucositis is defined as inflammation of oral mucosa resulting from cancer therapy typically manifesting as atrophy, swelling, erythema and ulceration. The condition may be exacerbated by local factors, such as trauma from teeth, or microbial colonization. The term stomatitis refers to any inflammatory condition of oral tissue, including mucosa, dentition/periapices, and periodontium. Stomatitis thus defines a broader range of pathoses of oral tissues, including mucositis.

A number of instruments to evaluate the observable, subjective and functional dimensions of oral mucositis are available.4 In addition, patient-reported outcomes of mouth and throat soreness have been developed.[5], [6]

Traditionally, mucosal toxicities have been separated by site of occurrence and studied accordingly. However, new insights have led to the realization that cancer treatment-induced mucosal damage affects the entire alimentary tract. Therefore, terminology has been introduced to describe this cancer therapy-associated mucosal injury, such as alimentary mucositis and mucosal barrier injury.[7], [8]

Section snippets

Pathobiology

Significant progress has been made in understanding the pathobiology of mucositis. A biological model for chemotherapy- and radiotherapy-induced oral mucositis proposed by Sonis,9 appeared to be more generally applicable to alimentary mucositis.[4], [10] What was once thought to be a simple reflection of direct epithelial damage induced by cytotoxic therapy is now considered to be a complex phenomenon that also affects the connective tissue. The model includes events that have been described in

Chemotherapy-induced versus radiation-induced mucositis

While there is similarity in the cellular events of chemotherapy- and radiation-induced mucositis, the biological pathways may be slightly different.11 Chemotherapy is administered systemically, whereas radiation therapy affects a specific body area. In addition, there are differences in the kinetics of treatment, affecting the clinical course (Fig. 1).[12], [13] Chemotherapy may be delivered over a short time, in which case the injury to mucosal tissues tends to be acute. Chemotherapy-induced

Prevalence and risk factors

Development of mucositis depends on a number of factors, related to both therapy and patient characteristics. Some potential risk factors have been identified, while others remain obscure.14 Treatment variables that may affect the prevalence and the severity of mucositis include the type, dose, and schedule of systemic cytotoxic medications, radiation dose and field, and concomitant use of chemotherapy and radiation. The majority of patients treated for head and neck cancers or those receiving

The impact of mucositis

A significant number of patients report oral mucositis as the most debilitating and troublesome adverse effect of cancer therapy.[21], [22] Prospective studies indicate that virtually all patients treated for head and neck cancer developed mouth and throat soreness of such severity that it reduced quality of life.[23], [24] Opioid analgesics did not always adequately palliate mucosal pain, and may lead to other problems such as dry mouth and constipation. In addition to its significant

Oral ulceration with a non-mucositis etiology

Other oral lesions may develop in the cancer patient that can complicate the diagnosis of mucositis. For correct diagnosis it is mandatory to have information about stomatotoxic therapies and prophylactic medications, peripheral blood counts and the time of onset as well as the location of the lesions. Frequent oral inspection to detect lesions at an early stage is helpful for diagnosis and successful management. Fungal and viral infections are the most common, but other microbial culprits may

Management

As mucositis became increasingly a dose-limiting toxicity, attempts to prevent and treat it gained momentum in the scientific and clinical environments. Unfortunately, most studies to date have had significant limitations and the available prophylactic and therapeutic strategies are limited. Systematic reviews of the literature have led to the publication of clinical practice guidelines.[37], [38], [39], [40], [41], [42], [43]

Selected interventions have met some success and these include

Concluding remarks

International collaboration between multidisciplinary basic researchers and clinicians has been crucial to a better understanding of mucositis and has led to a joint approach towards improving patient management.[4], [37], [38] Nevertheless, what we currently have to offer to patients to manage mucositis and oropharyngeal pain is still inadequate.[48], [23] Ongoing research into patient-reported outcomes is important and new techniques to detect mucositis at a subclinical stage are promising.49

Conflict of interest statement

Judith E. Raber-Durlacher occasionally lectures for EUSA Pharma. None of the other authors has any financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work.

Acknowledgment

We want to acknowledge the significant contribution of Professor S.T. Sonis to this review paper. The Multinational Association for Supportive Care in Cancer provided a travel stipendium to J.E.R.-D to present this paper.

References (49)

  • S.T. Sonis et al.

    Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients

    Cancer

    (2004)
  • P. Stiff 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 bone marrow transplantation (HSCT)

    Bone Marrow Transplant

    (2006)
  • J.B. Epstein et al.

    Longitudinal evaluation of the oral mucositis weekly questionnaire-head and neck cancer, a patient-reported outcomes questionnaire

    Cancer

    (2007)
  • D.E. Peterson et al.

    Alimentary tract mucositis in cancer patients: impact on terminology and assessment on research and clinical practice

    Support Care Cancer

    (2006)
  • N.M. Blijlevens et al.

    Mucosal barrier injury: biology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview

    Bone Marrow Transplant

    (2000)
  • C. Scully et al.

    Oral mucositis: a challenging complication of radiotherapy, chemotherapy, and radiochemotherapy. Part 1, pathogenesis and prophylaxis of mucositis

    Head Neck

    (2003)
  • A. Vissink et al.

    Prevention and treatment of the consequences of head and neck radiotherapy

    Crit Rev Oral Biol Med

    (2003)
  • S.T. Sonis

    A biological approach to mucositis

    J Support Oncol

    (2004)
  • S.T. Sonis

    Regimen-related gastrointestinal toxicities in cancer patients

    Curr Opin Support Palliative Care

    (2010)
  • K. Takahashi et al.

    Oral mucositis in patients receiving reduced-intensity regimens for allogeneic hematopoietic cell transplantation: comparison with conventional regimen

    Support Care Cancer

    (2009)
  • K. Robien et al.

    Predictors of oral mucositis in patients receiving hematopoietic stem cell transplants for chronic myelogenous leukemia

    J Clin Oncol

    (2004)
  • K. Bogunia-Kubik et al.

    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)
  • N. Blijlevens 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)
  • L.A. Bellm et al.

    Patient reports of complications of bone marrow transplantation

    Support Care Cancer

    (2000)
  • Cited by (183)

    View all citing articles on Scopus
    View full text