HYPOPHARYNGEAL CANCER TREATMENT INFORMATION

 

Hypopharyngeal cancer is a term used for tumors of this subsite of the upper aerodigestive tract, and like most other subsite designations, this is an anatomic rather than pathophysiologic distinction within the group of head and neck malignancies. The hypopharynx is the region between the oropharynx above (at the level of the hyoid bone) and the esophageal inlet below (at the lower end of the cricoid cartilage). Embryologically, the larynx interjects into the hypopharynx anteriorly, and is therefore considered a separate structure.

Early-stage hypopharyngeal cancers tend to be asymptomatic. Most patients, therefore, have no symptoms to bring them to medical attention until their disease is advanced, at which point the prognosis is poor.

    * Prognosis varies with the stage. The 5-year survival with small (T1-T2) lesions is about 60%, but with T3-T4 lesions or multiple node involvement, survival falls to 17-32%. Five-year survival for all stages is approximately 30%.    * Morbidity and mortality are predominantly due to the primary tumor itself causing pain, bleeding, poor swallowing (with subsequent malnutrition), or aspiration. Very advanced tumors may cause airway obstruction as they grow into the larynx.    * Laryngectomy is often needed, leading to permanent loss of voice and permanent tracheostomy. Functional problems from surgical or radiation treatment can include swallowing dysfunction, recurrent aspiration pneumonias, neck fibrosis, facial edema, and pain.

    * Neck mass: Cervical lymph node metastases occur as the presenting symptom in approximately 50% of cases.    * Sore throat              o Typically, it is unilateral and well localized.          o Often, pain radiates to the ears.          o Patients commonly undergo one or more courses of empiric antibiotics without response.    * Hoarseness: This indicates either involvement of the recurrent laryngeal nerve, which runs deep to the anterior wall of the pyriform sinus, or direct invasion of the larynx.    * Dysphagia.              o Tumor invasion often causes a combination of painful swallowing (odynophagia) and neuromuscular dysfunction (dysphagia).          o Aspiration occasionally is seen.          o Weight loss and malnutrition are common at presentation.

    * Otalgia: Referred pain to the ear is mediated by branches of the tenth cranial nerve. Invasion of the laryngeal nerve causes spread of neuropathic impulses to the auricular nerve (sensory to posterior external auditory canal and back of pinna).    * Hemoptysis    * Halitosis: Fetid breath is due to saprophytic bacterial overgrowth in fungating necrotic tumors.

The cause (etiology) of squamous cell cancers is similar for most anatomic subsites. Tobacco and ethanol are the principle carcinogens responsible. Long-term exposure causes progressive cellular dysregulation by alteration of tumor suppressor genes such as TP53, amplification of proto-oncogenes such as cyclin D1, and damage to regulatory factors such as transforming growth factor–beta (TGFb) and retinoic acid receptors. The progression from normal mucosa to cancer correlates with accumulation of genetic abnormalities.

The role of human papilloma virus (HPV) in cancers of the hypopharynx is unclear, although it may play more of a role in cancers of the oropharynx and oral cavity. Nonsmokers with cancers of the head and neck are more likely to have detectable HPV, although this is less common than hypopharyngeal cancer in persons who smoke.

    * Clinically, the mucosa first develops dysplastic lesions that may appear white (leukoplakia) or red (erythroplasia), and with time and continued carcinogen exposure, lesions can develop into frank malignancy.    * Nutritional and metabolic deficiencies are implicated in rare instances. Plummer-Vinson syndrome, mucosal webbing of the postcricoid area with iron deficiency, is associated with a higher incidence of cancer in that region. This is most common in women from northern Europe, including nonsmokers. The pathophysiology is not clear.    * Genetic factors are under investigation. Heritable polymorphisms of expression of enzymes that activate tobacco-related protocarcinogens (eg, aryl hydrocarbon hydroxylase) and detoxify carcinogens (eg, glutathione S-transferase) have been identified. Certain polymorphisms in the alcohol dehydrogenase genes may increase the risk of oral and pharyngeal cancers related to alcohol consumption. Racial differences in the metabolism of carcinogens may be a possible cause of the increasing incidence in African Americans.    * Clinical testing for peripheral, blood lymphocyte, chromosome fragility shows promise for identifying individuals at high risk of primary and secondary head and neck cancers, but it is still investigational.    * Deficient DNA repair mechanisms increase susceptibility to head, neck, and other cancers. Clinically recognized syndromes include xeroderma pigmentosum, Bloom syndrome, ataxia-telangiectasia, and Fanconi anemia. Head and neck cancers are not constituents of the most common cancer family syndromes, which include nonpolyposis colorectal cancer, Li-Fraumeni, or BRCA1/BRCA2 mutation kindreds.

Summation of examination and radiographic findings into prognostic categories, using tumor (T), nodal (N), and metastatic (M) categories, assists in treatment selection and planning.

    * Tumor category              o T1 - Tumor in 1 subsite of hypopharynx and less than 2 cm          o T2 - Tumor in 1 subsite of hypopharynx and greater than 2 cm but less than 4 cm, or tumor invades more than 1 subsite of hypopharynx or an adjacent site, and without fixation of larynx          o T3 - Tumor greater than 4 cm or with fixation of larynx          o T4a - Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophagus, or central compartment soft tissue

            T4b - Tumor invades prevertebral fascia, encases carotid arteries, or involves mediastinal structures    * Nodal category              o N0 - No regional nodes involved          o N1 - Single ipsilateral node involved, not greater than 3 cm          o N2a - Single ipsilateral node, greater than 3 but less than 6 cm          o N2b - Multiple ipsilateral nodes, none larger than 6 cm          o N2c - Multiple bilateral or contralateral nodes, none larger than 6 cm          o N3 - Any node larger than 6 cm    * Metastatic category              o M0 - No distant metastases          o M1 - Distant metastases present    * Stage grouping              o Stage I - T1 N0 M0          o Stage II - T2 N0 M0          o Stage III - T3 N0 M0; T1-3 N1 M0          o Stage IVA - T4a N0-1 M0; T1-4a N2 M0          o Stage IVB - T any N3 M0, T4a N any M0          o Stage IVC - T any N any M1

    * An experienced otolaryngologist (head and neck) surgeon working with radiation and medical oncologists in a team approach should direct surgical care of the patient. T1-T2 tumors show similar outcomes with radiation or surgery. The timing of surgery, chemotherapy, and radiation should be determined by the treating physicians based on the staging and clinical features of the tumor.    * Medical and technical operability needs to be determined by addressing the following questions:              o Can the whole patient tolerate curative surgery?          o Can the cancer be resected with clear margins and acceptable morbidity?    * The extent of surgery for primary tumors depends on the local size and location.   

          o Well-localized T1-T2 lesions can be amenable to partial pharyngectomy or laryngopharyngectomy.          o Laryngopharyngectomy is more commonly required for T3-T4 tumors.          o Reconstruction of the pharynx can involve a gastric pull-up, jejunal transposition, skin graft, myocutaneous flap, or a combination of these.    * Neck dissection is generally performed if there is a N1-N3 palpable adenopathy or clinical N0 neck but a T3-T4 primary tumor.

    * Hypopharyngeal cancers generally have a poorer prognosis than other head and neck subsites, partly due to frequent late-stage presentation.              o Prognosis varies with stage. With small (T1-T2) lesions, the 5-year survival rate is about 60%, but with T3-T4 lesions or multiple node involvement, this rate falls to 15-30%.          o Distant metastatic disease develops in approximately 25% of patients. The lungs, liver, and bones are the principle organs affected.          o The principle cause of death is local tumor recurrence. Distant metastases, second primary cancers, and comorbid diseases are secondary causes.

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