______________________________________________ Oral Cancer and Complications of Cancer Therapies
therapy regimens for squamous cell carcinoma patients range between 5,000 and 7,000 cGy, most patients will encounter undesirable side effects [38]. The area at which the radiation is targeted will influence the types of side effects experienced by the patient. Concurrent antibody therapy with cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, may be considered for patients in whom chemotherapy is contraindicated, as many oral squamous cell carcinomas show moderate to high levels of EGFR expression [39; 40]. It has been suggested that side effects may be minimized if the agent is administered between the hours of 11 a.m. and 3 p.m., due to the circadian rhythm of the oral mucosa [41; 42]. This time frame is hypothesized as being ideal for maximum therapeutic effect and reduced toxicity of both cetuximab and radiotherapy treatments. CHEMOTHERAPY For patients with oral cancer, chemotherapy is recommended only as an adjunct to radiation and/or surgical therapy [2]. Chemotherapy alone has not been shown to have the same effi- cacy against oral cancer as with other cancers. Chemotherapy is recommended as an adjunct in the treatment of oral cancer in order to [2; 14]: • Reduce and/or inhibit distant metastasis • Reduce tumor size prior to surgery • Sensitize malignant tissue to radiotherapy Additional research to determine the most effective use of chemotherapy as part of the overall treatment plan for oral cancer is necessary.
Oral mucositis is the most common intraoral side effect of radiotherapy and usually has an onset in the second week of therapy [43; 44]. Mucositis affects nearly 80% of all patients who undergo head and neck radiotherapy and occurs in four phases [43]. The inflammatory phase is begun as ionizing radia- tion causes the generation of free radicals. The disruption of the normal sequence of turnover and stratification from the basal cell layer is a continuum into the epithelial phase. The ulcerative phase features ulcerations of varied dimensions on any mucosal surface. The consequent pain can be so intense that patients may have difficulty eating at a time when adequate nutrition is life sustaining. Patients with removable complete or partial dentures may be unable to wear them, further com- plicating their ability to masticate and swallow. The denuded mucosal surfaces also are a portal of entry for organisms of an altered oral microflora. This, coupled with a host whose immu- nocompetence is challenged, can lead to systemic bacterial or fungal infections that may be fatal. Severe mucositis mandates that radiotherapy be postponed until adequate healing of the epithelium occurs. The healing phase may take several weeks after the last radiotherapy treatment [45].
A Cochrane Review found that oral cryotherapy leads to large reductions in oral mucositis of all severities in adults receiving 5FU for solid cancers. (https://www.cochranelibrary.com/ cdsr/doi/10.1002/14651858.CD011552.
pub2/full. Last accessed December 20, 2024.) Level of Evidence : Meta-Analysis
ORAL COMPLICATIONS FROM RADIOTHERAPY
The National Cancer Institute has developed a Mucositis Scale to allow for the basic categorization of the mucositis lesions according to severity [46]. Grade 1 is defined as the absence of symptomatic mucositis or mild symptoms. Minimal mucositis, grade 2, involves moderate pain that does not greatly interfere with food intake but may necessitate a slightly altered diet. A grade 3 (severe) reaction is present when extreme pain causes feeding to become difficult. At this grade, the patient can only tolerate a liquid diet. When the mucosal ulcerations are deep or necrotic and bleed spontaneously, a grade 4 level has been attained. This level of mucositis is considered life-threatening. Patients with grade 4 mucositis may require intravenous fluids, analgesics, and antibiotics in a hospital setting until they are medically stabilized. Even if radiotherapy has been completed, the patient should still be followed closely to assure complete healing of all lesions. If radiotherapy has been interrupted because of the severity of mucositis, the cumulative dose of radiation that remains may be fractionated into smaller daily doses. Grade 5 is death [46].
The earliest complication seen after radiotherapy is damage to the skin and hair follicles that lie in the direct path of radia- tion, known as the treatment portal. Hair follicles are highly radiosensitive, and hair will cease to grow and may fall out. This is a temporary loss that may take weeks or months to reverse. The skin in the portal area may become cracked, reddened, and ulcerated to the extent that radiation therapy should be postponed. This problem is also reversible upon cessation of radiotherapy. In addition, radiotherapy can result in negative effects on oral health. MUCOSITIS Normal oral epithelium regenerates every three to four days. The outer squamous cells are replenished by cells made anew at the basal layer. The cellular regeneration corresponds with a high level of mitotic activity. Radiotherapy cannot distinguish the mitotic activity between malignant cells and those needed to replenish the oral epithelium; it is cytotoxic to both groups of cells, resulting in mucositis.
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