46 Oral and Dental Complications of Oral Cancer Treatment
Oral cancer therapy may result in acute and chronic oral/dental consequences which include (but are not limited to) mucositis, hyposalivation/xerostomia, oral infections, neurotoxicity/neuropathy, orofacial pain, taste/smell disorders, and osteoradionecrosis of the jaw. This chapter will discuss in depth on the epidemiology, clinical presentation, diagnosis and evaluation of each dental related complications post oral cancer therapy, as well as treatment considerations to improve patients’ quality of life. A collaborative interdisciplinary team is necessary to prepare appropriate treatment plans for patients before the commencement of oncologic therapy.
Oral cancer therapeutic regimens may result in acute and chronic oral and dental sequelae, which indubitably affect a cancer survivor’s quality of life. These manifestations may include, but are not limited to, mucositis, hyposalivation and/or xerostomia, osteoradionecrosis (ORN) of the jaw, chemotherapy-induced neuropathy, dysphagia, dysgeusia, an increased risk for developing dental decay, trismus, orofacial pain, mucosal lesions, radiation fibrosis syndrome, and oral infections. 1 – 60 It is, hence, essential that the patient’s oncology team be knowledgeable in the evaluation and management of the oral and dental manifestations associated with head and neck oncologic therapy.
Prior to commencement of therapy, a patient diagnosed with oral cancer should be evaluated by a dental oncologist to help reduce the patient’s risk for developing head and neck manifestations associated with his/her proposed oncologic treatment. In addition, clinicians should discuss the patient’s proposed cancer treatment with the patient’s oncology team and have a detailed discussion with the patient about oral hygiene instruction, the oral and dental sequelae of his/her proposed therapy, and methods to help reduce the patient’s risk for developing the associated manifestations. This chapter focuses on the epidemiology, clinical presentation, diagnosis and evaluation of the dental complications of oral cancer therapy as well as treatment considerations and approaches.
46.2 Oral Mucositis
Oral mucositis is one of the most common complications of head and neck cancer therapy and often reported by patients as the single most debilitating complication of treatment. 24 Sonis et al (2003) reports that chemotherapy and/or radiation therapy (RT) may induce mucosal injury both by direct damage to epithelial cells lining the oral mucosa and also by upregulating an inflammatory response resulting in oral mucositis. 19
While risk factors may dictate the severity, almost all patients treated with RT for head and neck cancer are expected to develop some degree of oral mucositis. 6 , 25 Severe oral mucositis has been reported in 29 to 66% of all patients receiving head and neck RT. Increased incidence of mucositis is noted in patients with a primary tumor in the oral cavity, oropharynx, or nasopharynx, those receiving adjunctive chemotherapy, those receiving RT doses = 5,000 cGy, and those receiving altered fractionation RT. Oral mucositis has been reported to occur in approximately 20 to 40% of patients receiving conventional chemotherapy and 80% of patients receiving high-dose chemotherapy. 6 , 7 , 25
46.2.2 Clinical Presentation
Oral mucositis presents as erythematous and ulcerative lesions affecting the oral mucosa. 1 , 19 , 25 Signs and symptoms of oral mucositis often vary throughout the progression of head and neck cancer therapy. At the beginning of head and neck RT, cumulative doses as low as 10 Gy may lead to mucosal erythema and superficial tissue sloughing. Patients may complain of discomfort and pain that is similar to a food or chemical burn, although the mucosa at this stage remains intact. As the cumulative doses increase to 20-30 Gy, the mucosa begins to break down resulting in ulcerative mucositis. At this stage, patients may report severe pain and ulcerative lesions present with uneven borders and a pseudomembrane covering, often consisting of bacterial infiltrates and necrotic tissue (▶ Fig. 41.4). This stage of severe pain may persist throughout RT and up to 3 weeks post RT.
Chemotherapy-induced ulcerative mucositis presents at earlier stages of therapy following a more acute course. The initial mucosal changes often present within 5 days of chemotherapy drug infusion and progress to the severely painful ulcerative colitis stage by day seven of therapy. The lesions may persist for 7 to 10 days and commonly heal by 3 weeks post initiation. 25
46.2.3 Diagnosis and Evaluation
Multiple grading systems attempt to categorize the sequential clinical presentations of oral mucositis (▶ Table 46.1). The World Health Organization (WHO) grading system is based on the clinical presentation and patients’ functional status. Other grading systems consider the pathological changes in mucosal tissue. 25 , 36
46.2.4 Anatomic Considerations and Approaches
RT and chemotherapy may lead to mucosal injuries that manifest in different locations. RT-induced mucositis is localized to the field of high-dose RT, while chemotherapy-induced mucositis may affect the entire gastrointestinal tract. 1 , 5 , 36 Though mucositis may affect the entire oral cavity, it commonly affects the movable mucosa (buccal mucosa, lingual mucosa, floor of the mouth, and soft palate) but rarely presents on keratinized tissue (hard palate, dorsal tongue, and gingiva). 1 , 25
46.2.5 Treatment Considerations and Approaches
The Multinational Association of Supportive Care in Cancer (MASCC) recommendations are made only if strong evidence supports effectiveness in the respective treatment settings (▶ Table 46.2). Interventions that are supported with weaker evidence are also listed as suggestions in the detailed review published by MASCC and the Cochrane Group but not included in this chapter. 5 , 6
Saliva serves many critical functions that assist in maintaining equilibrium in the oral cavity including playing a vital role in digestion, mastication, deglutition, gustatory sensation, and host defense. 1 – 4 , 37 , 43 Head and neck RT in cumulative doses greater than 25 to 30 Gy may result in salivary tissue damage and temporary or permanent salivary gland dysfunction. 1 , 37 – 39 , 41 , 43
Xerostomia, the subjective sensation of dry mouth, during head and neck RT has a reported prevalence of 93%, which contrasts with the reported prevalence of 6.0% prior to the commencement of RT. 37 Xerostomia is one of the most common late toxicities reported by head and neck cancer patients.
46.3.2 Clinical Presentation
Patients with decreased salivary flow often complain of xerostomia. In addition, they may present with ropey, thick saliva or complain of increased thirst. Reduced salivary flow increases the a patient’s risk for developing dental demineralization, dental decay, oral infections, dysgeusia, dysphagia, dysarthria, halitosis, oral soreness and burning, and inability to wear dentures. 1 – 4 , 38 , 39 , 41 , 43 The varying symptoms of hyposalivation and/or xerostomia contribute to a reduced quality of life which may affect an individual’s psychological and physical health. 1 – 4 , 38
46.3.3 Diagnosis and Evaluation
Damaged salivary glands may lead to altered saliva production resulting in hyposalivation, traditionally defined as resting saliva flow rate of < 0.1 ml/minute and/or stimulated saliva flow rate of < 0.5 ml/minute. 20 , 21 , 43 While xerostomia is the subjective measure of dry mouth, hyposalivation serves as an objective measure for assessing salivary flow. 40 , 43 Xerostomia may be assessed by both patient self-reporting instruments and practitioner-observer assessments; however, patient self-reported assessments are often considered more reliable. 40 Hyposalivation does not always correlate with the subjective symptoms of xerostomia.
46.3.4 Anatomic Considerations and Approaches
The major salivary glands (parotid, submandibular, and sublingual) are commonly included or in close proximity to target radiation fields. Parotid glands are most often irradiated in conventional RT due to their anatomical location. 7 , 39 In addition, serous glands are often more radiosensitive than mucus glands. 1 , 2
46.3.5 Treatment Considerations and Approaches
Reversibility of reduced salivary flow is dose-limited and depends on the field of radiation. Oral health education, prevention, and care are important in maintaining a healthy dentition and preventing further dental complications in oral cancer patients. At the treatment planning stage, patients should be educated on the risks of hyposalivation and loss of protective mechanisms of saliva. Patients should be evaluated by a dentist for dental decay and infections and treated prior to RT. Further dental preventative measures include fluoride-containing mouth rinses, fluoride gels and toothpastes, over-the-counter salivary gland stimulants, sialogogues, and in some cases parasympathomimetics. 38 , 41 – 43 Pilocarpine hydrochloride, a parasympathomimetic, has been reported as an effective treatment for radiation-induced xerostomia; however, it may be associated with various side effects due to the parasympathetic stimulation. 38 , 41 , 42
Surgical Options and Approaches
Salivary gland transfer is a surgical procedure that may prevent RT-induced xerostomia and maintain salivary flow rates after RT. Salivary glands that are within the radiation field are surgically transferred to another anatomical space and shielded. For example, submandibular glands may be transferred to the submental space before beginning RT and shielded. The procedure has been reported as highly effective in preventing the incidence of xerostomia in patients receiving RT to treat head and neck cancers. It has also been reported to improve quality of life in these patients. 22 , 23 , 39 , 41
46.4 Oral Infections
Oral candidiasis is extremely common in patients undergoing cancer therapy; however, reports on the incidence, prevalence, and epidemiology are limited. 1 , 3 , 4 , 9 , 10 A systematic review from 2010 reported that 50% of head and neck cancer patients presented with oral fungal colonization prior to the commencement of RT. 9 , 10 During RT, 74.5% of the patients presented with oral fungal colonization which remained constant immediately following the completion of RT. 9 , 10 Of the 74.5% of patients with colonized oral fungi, 37.4% of the patients presented with an oral fungal infection during treatment. After RT, 32.6% presented with oral fungal infection. 9 , 10 Oral candidiasis may present with pain, dysgeusia, malnutrition, anorexia, and dysphagia. 1 , 2 , 4 Patients that are undergoing immunosuppressive therapy, such as chemotherapy, are at an increased risk for the progression of oral candidiasis to oropharyngeal candidiasis and systemic fungemia which can be fatal. 9 , 10
46.4.2 Clinical Presentation
Bacterial infections in the oral cavity may present as necrotizing ulcerative gingivitis, periodontal infections, odontogenic infections, deep space infections, sialadenitis, or infections secondary to oral mucositis. 3 , 4 , 16 , 17 Oral ulcerations associated with mucositis may provide a nidus for bacterial proliferation and growth. 1 , 4 , 14
The most common fungal infections affecting the oral cancer patients may be attributed to oral candidiasis with 90% of candidal infections being associated with Candida albicans; nonetheless, other candidal strains have been identified in oral candidiasis including fluconazole-resistant candidal strains. 1 , 4 , 9 , 10 Oral fungal infections may also be attributed to other fungi; yet, these infections are less common than oral candidiasis. 1 , 4 , 13 Oral candidiasis may present in various forms including, but not limited to pseudomembranous candidiasis, erythematous candidiasis, mucocutaneous candidiasis, chronic multifocal candidiasis, and angular cheilitis. Erythematous and pseudomembranous candidiasis are most common forms that present in the oncology patient population. 9 Oral candidiasis presentation ranges from intraoral adherent white plaques that may be removed with a gauze to intraoral red lesions in which the tongue may appear red and devoid of filiform papillae. Candidiasis may also present at the commissures of the lips as red, fissured lesions that may be painful. 3 , 4 , 13 Occasionally, angular cheilitis may be due to the presence of both Staphylococcus aureus and a Candida infection, and thus should be treated with both an antibiotic and antifungal ointment. 4