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Epidemiology
The oropharynx is the posterior continuation of the oral cavity and connects with the nasopharynx (above) and laryngopharynx (below). It is located between the soft palate superiorly, and the hyoid bone inferiorly. The main sites of the oropharynx consist of the posterior and lateral pharyngeal wall, faucial arches, tonsillar fossa (TF), soft palate (SP), and the base of tongue (BOT). These structures play a crucial role in swallowing and speech. By obstructing the “air space” or by infiltrating muscles or nerves, locally advanced oropharyngeal tumors can significantly impede these functions. The same holds for intensive treatment regimen: it can cause deformities and/or impairment of particular functional (sub) units, resulting eventually in severe (late) side effects. It has long been known that patients with a history of smoking or excessive consumption of alcohol are believed to be at increased risk for developing cancer in the oropharynx (31,37). Overall these cancers comprise less than 0.5% of all cancers in men in the United States, which amounts to approximately 5000 new cases each year (319). According to the Surveillance, Epidemiology, and End Results report of the National Cancer Institute, in 2001 the age-adjusted incidence was 1.5 per 100,000 white men and 3.2 per 100,000 black men (271). These cancers more often afflict men (4:1); they are diagnosed most frequently in the sixth and seventh decades of life. Oropharyngeal cancers are readily accessible to clinical examination and staging. Historically, in the early stage and in the moderately advanced tumors, radiation therapy (RT) has been the preferred therapy mode because of its organ function-preservation properties (300,321). Most (±95%) oropharyngeal cancers are squamous cell carcinomas (SCC). Although reports can be found of other histologic subtypes (1,14,72,93,158), such as minor salivary gland tumors, lymphoepitheliomas, malignant lymphomas, mesenchymal tumors, or metastases from other extracranial tumor sites, these will not be discussed in great detail as they are considered beyond the scope of the present chapter.
Anatomy
The SP, anterior faucial pillar, and the retromolar trigone are embryologically connected to the oral cavity. However, because of their clinical behavior, tumors of these structures are preferably classified with oropharyngeal malignancies. The inferior part of the TF is referred to as the glossopalatine sulcus (Fig. 42.1). The lateral border of the retromolar trigone extends upward into the buccal mucosa, medially it blends with the anterior tonsillar pillar. Its base is formed by the last lower molar and the adjacent gingivolingual surface. The lateral walls of the oropharynx are limited posteriorly by the TF proper and the posterior tonsillar pillar. The anterior and posterior tonsillar pillars are the folds of mucous membrane that cover the underlying glossopalatine and pharyngopalatine muscles, respectively. Deep to the lateral wall of the TF are major vessels (Figs. 42.2 and 42.3) and muscular components such as the superior constrictor muscle, the upper fibers of the middle constrictor muscle, the pharyngeus and stylopharyngeus muscles, and the glossopalatine and pharyngopalatine muscles. Stratified squamous epithelium covers all of these structures. The tonsil has a heavy lymphoid network. The pharyngeal wall is related to the second and third cervical vertebrae. Nerve supply is from the cranial nerves IX and X. The BOT lies posterior and inferior to the palatoglossal arch. It is bounded anteriorly by the circumvallate papillae, laterally by the glossopharyngeal sulci and oropharyngeal walls, and inferiorly by the valleculae and the pharyngoepiglottic fold. Embryologically, its epithelium is derived from the entoderm, unlike that from the oral tongue (ectoderm). The body of the BOT is formed by thick muscles, the genioglossus, styloglossus, palatoglossus, and hypoglossus muscles. The muscles originate from the margins of the mandible and are attached to the hyoid bone. The blood supply and the innervation are by the lingual arteries and hypoglossal nerve, respectively.
Natural History
In general, tumors of the anterior tonsillar pillar and soft palate are better differentiated and biologically less aggressive than those of the TF. For example, 50% to 60% of patients with primary tumors in the anterior tonsillar pillar, retromolar trigone, and SP had necks with clinically negative findings, in contrast to only 24% of those with TF primaries (149). Lesions of the TF (231), retromolar trigone (39), and BOT tend to grow more extensively. Perez et al. (234) observed that the primary tumor was confined to the TF in only 5.4%. Byers et al. (171) described 14% mandibular invasion in carcinomas of the retromolar trigone. At diagnosis, 75% of BOT cancers have invaded adjacent structures, including the glossopharyngeal sulcus, pharyngeal wall, larynx, and/or faucial arches. The most common complaint at presentation of tumors in the oropharynx is pain; this pain is either attributed to (severe) mucositis, deep infiltration of the tumor or is referred (Fig. 42.4). However, patients with primary tumors of the oropharynx can also be asymptomatic or have only vague discomfort at presentation. BOT tumors, for example, typically grow insidiously. Because the BOT is devoid of pain fibers, they are mostly asymptomatic until they have progressed significantly. With local advancement and/or with infiltration of the pterygoid muscles, patients can experience trismus and, ultimately, bleeding or swallowing problems, or can have difficulty with speech.
Diagnosis is typically established by clinical examination in the outpatient clinic and/or examination under general anesthesia, including morphologic confirmation (biopsy) of the lesion and tattooing of the clinical target volume (CTV). In the Erasmus Medical Center—Daniel den Hoed, Rotterdam (Erasmus MC), at the time of diagnosis/staging, with the patient still under general anesthesia, the lesion is frequently marked with marker seeds. This enables the extensions of the lesion to be visualized on x-ray films. From a series of patients implanted with platinum markers, we found, for example, that the TF significantly moves during swallowing and even in rest (because of respiration). Maximum excursions in rest were found to be 3.6 mm. This type of information contributes to a more
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accurate determination of the planning target volume (PTV) margin (Figs. 42.5 and 42.6). Conventionally, platinum (Pt) or gold (Au) marker seeds were used, particularly for those patients to be boosted by brachytherapy (BT) (175). Because of significant scattering properties on computed tomography (CT), nonmetallic seeds are being tested. Panendoscopy can reveal synchronous second primaries. Ultrasound fine-needle aspiration biopsy has become an indispensable tool for pro diagnosis and for staging, especially where it concerns the lymph nodes. Multislice CT and magnetic resonance imaging (MRI) scans are now obligatory imaging tools. CT scanning with contrast enhancement using 2-mm slices is better for detecting lymph nodes and for bone detail. MRI is preferred for the evaluation of the parapharyngeal space. Axial slices are usually sufficient; sagittal MRI is helpful for detecting early pre-epiglottic space infiltration. CT combined with positron emission tomography scanning seems an extremely promising, powerful tool for diagnostic and simulation purposes, but is not yet available in every institution. Several textbooks contain helpful overviews (8,59,123,171,208,232).
Tumors are staged according to the American Joint Committee on Cancer classification system (Table 42.1) (6). Dentulous patients are at increased risk for caries and osteoradionecrosis from the reduction and qualitative change of salivary flow, change in pH, and proliferation of bacteria believed to be responsible for caries. Panorex x-ray films, identification of nonrestorable teeth for pretreatment extraction, dental trays for fluoride rinse, protection against scatter radiation, as well as education about long-term oral hygiene, should be engaged before RT and/or chemotherapy (CHT) is applied. In fact, the quite common development of osteoradionecrosis in the past (17) should be prevented by adequate measures. Finally, given the complexity of head and neck tumors, all patients should be
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formally discussed in a head and neck tumor board, with or without the patient being present, before the initiation of any treatment.