Mucositis
Background
Oral mucositis (OM) is a common complication of cytotoxic chemotherapy. OM may defined as an inflammatory process involving the mucous membranes of the oral mucosa and gastrointestinal tract.1 Incidence rates are estimated at 5% to 40% in patients receiving cytotoxic chemotherapy for solid tumors.2
Pathobiology
Historically, it has been believed that OM resulted from damage to the epithelium by cytotoxic or radiation therapy. Chemotherapy agents target nonspecific proliferative tumor cells, but they are not able to differentiate between tumor cells and rapidly dividing normal cells. Ultimately, basal cells are injured and die, with no new cells to replace the damaged cells, leading to a thinning and atrophic mucosa, with ulceration development.3
Sonis3 have developed a pathobiologic model for the development and resolution of mucositis, which involves five phases:
- Initiation
- Upregulation and message generation
- Amplification and signaling
- Ulceration
- Healing
The initiation phase includes the generation of reactive oxygen species (ROS) caused by chemotherapy or irradiation, which leads to biologic events and subsequent mucosal injury. Upregulation and message generation occurs as a result of the activation of transcription factorsby both radiation therapy and chemotherapy. Once activated, they control the synthesis of proteins (cytokines), which target specific tissue, resulting in further tissue damage. During the signaling and amplification phase, there is direct damage to the cells by the cytokines, with tumor necrosis factor (TNF)-α activation, creating a feedback loop that leads to additional proinflammatory changes. Damage here occurs beneath the mucosal surface. Ulceration is most clinically evident, extending from the epithelium to the submucosa, with exposure of neuron endings leading to pain. The ulcerated region undergoes colonization that penetrates into surrounding tissue, leading to stimulation of proinflammatory cytokines. In the healing phase, the surface of the ulcer becomes covered with epithelium, leading to layering of cells and establishment of normal healthy mucosa.1,3,4
Risk Factors
Early identification of patients at risk for developing mucositis is critical. Preventive measures and management strategies may be incorporated into the treatment plan. Risk factors have been classified into 2 categories1,4
Patient-related risk factors:
- Age (very young due to increased cell turnover rate and elderly due to delayed healing)
- Sex (data suggest that women may be at higher risk)
- Smoking
- Alcohol
- Previous cancer treatment
- Abnormal renal function
- Poor oral hygiene
- Low body mass index
- Decreased saliva production
Treatment-related risk factors
- Specific chemotherapy agents; eg, antimetabolites, antitumor antibiotics, alkylating agents
- Dose of chemotherapy agents and schedule
- Combined modality: radiation and chemotherapy carries greater risk
Assessment Tools
Accurate oral assessment is critical in the prevention and management of OM. A number of grading and assessment tools are available for assessing the oral cavity:
- The Oral Assessment Guide (OAG) focuses on changes in the oral cavity related to cancer treatment including function and tissue assessment
- The following assess the amount of tissue involved but do not include function:
- Oral Mucosa Rating Scale (OMRS)
- Oral Mucositis Index (OMI)
- Oral Mucositis Assessment Scale (OMAS)1
Additional guides to assessment tools to measure oncology-nursing sensitive outcomes may be accessed at: http://onsopcontent.ons.org/toolkits/evidence/Clinical/pdf/MucositisTools.pdf
Additionally, there are tools available for grading OM such as the National Cancer Institute Common Toxicity Criteria (CTC v.3) used by the World Health Organization. CTCAEv3.pdf. In version 3 mucositis is now under GI Events and listed as mucositis/stomatitis clinical exam and mucositis/stomatitis functional/symptomatic.
Clinical Guidelines
The Multinational Association of Supportive Care in Cancer (MASCC) and the International Society of Oral Oncology have developed guidelines for the evaluation, prevention, and treatment of OM. These guidelines may be accessed at http://www3.interscience.wiley.com/cgi-bin/fulltext/108069518/HTMLSTART.
Patient Care Management Protocols or Algorithms
The Oncology Nursing Society (ONS) has published an evidence-based practice quick reference card (ONS PEPcard) on the management of OM. This card may be accessed at http://www.ons.org/outcomes/volume2/mucositis/pdf/PEPCardShort_mucositis.pdf
References
- Eilers J, Million R. Prevention and management of oral mucositis in patients with cancer. Semin Oncol Nurs. 2007;23:201-212.
- Peterson D. New strategies for management of oral mucositis in cancer patients. J Support Oncol. 2006;4(2 suppl 1):9-13.
- Sonis ST. Pathobiology of mucositis. Semin Oncol Nurs. 2004;20:11-15.
- Cawley MM, Benson LM. Current trends in managing oral mucositis. Clin J Oncol Nurs. 2005;9:584-592.
Key Definitions
atrophic—wasting away or diminution
cytokines—a small protein released by cells that have specific effects on the interactions between cells, on communication between cells, or on the behavior of cells
epithelium—membranous tissue composed of one or more layers of cells separated by very little intercellular substance and forming most internal and external surfaces of the body and its organs
neuron—any of the impulse-conducting cells that constitute the brain, spinal column, and nerves
proliferative—growing and increasing in number rapidly
TNF-α—serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes
transcription factors—a protein that controls when genes are switched on or off whether genes are transcribed or not
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