1. DIAGNOSTIC EVALUATION
2. EXAMINATION UNDER ANESTHESIA (OPTIONAL) AND BIOPSY
3. DEFINITIVE TREATMENT
4. ADJUVANT TREATMENT
5. FOLLOW UP
6. BIBLIOGRAPHY

I. DIAGNOSTIC EVALUATION:

Clinical Evaluation:

• Complete history and physical examination
  
  Recording the presence and duration of symptoms such as facial pain or numbness, headaches, soreness of throat, otalgia, epistaxis, diplopia, hearing loss, trismus, dysphagia and hoarseness or other speech changes (nasality, "hot potato" voice). It should include history of risk factors such as the use of tobacco and alcohol, the occurrence and extent of weight loss and of all other medical conditions, as well as previous treatments such a surgery, radiation, chemotherapy or biologicals.

• Complete head and neck examination.
  
  Including a fiberoptic endoscopic examination of the nasal cavity, nasopharynx, hypopharynx, and larynx. Indirect mirror examination of the nasopharynx may be adequate in selected patients, but a fiberoptic endoscopic examination allows better evaluation of the fossae of Rosenmueller. Evaluation of cranial nerves with special attention to cranial nerves I, II, III, IV, V, and VI. Visual acuity and full extraocular motility should be documented. Evidence of proptosis or diplopia should be noted. The functional status of cranial nerves VII - XII should be documented. Document the mobility of the tympanic membranes and presence of serious otitis media. The status of the cervical lymph nodes should be noted indicating the number, location (level group I-V), mobility, size and relationship of the node(s) to adjacent structures.The staging of the primary and of the cervical lymph nodes must be documented.

• Biopsy of the primary tumor may be done under endoscopic guidance in the outpatient setting. Selected patients may require biopsy under general anesthesia.

• Histological evaluation allows the classification of the neoplasm according to the World Health Organization (WHO):
  
  

  WHO-1 =	well differentiated, moderately differentiated SCCa,
  WHO-2 =	non-Keratanizing tumors,
  WHO-3 =	undifferentiated carcinomas.

• Fine needle aspiration biopsy of suspected metastatic disease may be performed in selected cases. (Open surgical biopsy of suspected metastatic disease is not indicated unless FNAB is negative and clinical suspicion is strong)

Imaging Studies:

• Chest radiographs, PA and lateral

  Panoramic view (Panorex) of the mandible and/or dental X-rays.

  When necessary to adequately assess the status of the patient's dentition.

• Chest radiographs, PA and lateral

  To rule out (1) A synchronous pulmonary tumor, (2) Acute or chronic pulmonary disease (3) Metastatic tumor. Abnormal findings on chest x-ray or suspicious lesions need further imaging including a chest CT.

• CT scan

  A high resolution scan with axial and coronal views, as well as bony windows, provides better definition of the cortical bone.

• MRI of head and neck with and without gadolinium
  
  Including the nasopharynx, skull base, and neck, to assess the extent of the primary tumor within the nasopharynx and invasion of adjacent structures, such as the paraspinal muscles, infratemporal fossa, temporal bone, sphenoid sinus, bone marrow of the clivus, carotid artery, cranial nerves, and intracranial structures.

Laboratory Tests:

• Pre-anesthesia laboratory tests (according to institutional guidelines).

• Liver enzymes (Alk Phosphate, SGOT, SGPT)

• Epstein-Barr viral titers, including IgA antibodies to early antigen - diffuse (Ead) and viral capsid antigen (VCA), and anti-Epstein Barr nuclear antigen (EBNA). (Optional)

Consultations:

• Radiation Therapy
  
  In anticipation for radiotherapy as primary treatment

• Dental Consultation:
  
  To assess the status of the teeth and make recommendations considering that radiation therapy will be used. The evaluating dentist should be versed in the effects of radiotherapy on dentition. This evaluation should be done with knowledge of the treatment portals planned for the radiotherapy. 

• Internal Medicine, Cardiology, Anesthesiology:
  
  When a disease is present which may affect the use of general anesthesia or may influence therapeutic decisions.

• Neurosurgery:

       When resection of the skull base is anticipated.

• Interventional Radiology:
  
  When embolization of the tumor is necessary in preparation for surgery or for uncontrolled epistaxis or when cerebral blood flow studies are required during the preoperative evaluation. (e.g., Tumor involves the   extratemporal or intratemporal carotid artery and its resection is anticipated.)

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Patients who do not tolerate the nasopharyngoscopy and/or biopsy of the tumor in the office, will require examination and biopsy under anesthesia. Concomitant endoscopy of the larynx, hypopharynx and esophagus is indicated in patients at risk for the development of a synchronous primary (alcohol and tobacco abusers), or patients with symptoms related to the upper aerodigestive tract whose symptoms could not be elucidated during the office evaluation. Bronchoscopy is not needed in asymptomatic patient with normal chest x-ray.

Dental extractions when indicated may be carried out at this time.

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Primary tumor:

Radiation therapy is the mainstay treatment for nasopharyngeal carcinoma. Radiotherapy fields should encompass the primary site as well as the regional lymph nodes in both sides of the neck and retropharynx, even in patients without palpable nodal disease and regardless of the T stage (nasopharyngeal carcinomas are associated with a high incidence of overt and occult lymph node metastasis, irrespective of size of the primary tumor).

Because of the multiple adjacent vital structures, such as the pituitary gland, brain stem, temporal lobes, eyes, optic nerves, and temporomandibular joint, radiation therapy must be carefully planned and must be executed using multiportal techniques, using high-energy radiation with brachytherapy, when appropriate.

CT scan/MRI scan is repeated after 4 to 5 weeks of radiation therapy in order to plan the cone down or boost treatment, and again at the end of external radiation therapy to plan a brachytherapy boost, when appropriate.

At the present time, surgical treatment of primary nasopharyngeal carcinoma is not generally accepted. Surgery, utilizing various approaches to the skull base, is reserved for very selected patients with recurrent tumors and for some tumors of unusual histology such as chordomas, sarcomas and adenocarcinomas. Surgery, however, should be considered for persistent and/or recurrent tumors. Brachytherapy and stereotactic surgery are other alternatives for the treatment of recurrent or persistent disease.

Neck:

Radiation therapy is also the initial and main treatment for cervical metastasis to the lymph nodes. The radiation fields should include both sides of the neck (Levels II - V) and the retropharyngeal region.

A comprehensive neck dissection is performed only when palpable cervical metastases persist after completion of radiation. It is preferably carried out 6-8 weeks after completion of treatment if the primary tumor is controlled.

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Neo-adjuvant chemotherapy may be of value in the treatment of nasopharyngeal carcinoma. In addition to possibly improving survival, it may be helpful in those patients whose primary or nodal disease is so extensive that adequate radiation therapy is not possible without a high risk of injury to critical structures such as the optic pathways. Currently, however, chemotherapy should be used only under an IRB approved experimental clinical protocol.

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V.FOLLOW UP:

Follow-up evaluations are scheduled on an individual basis determined by the risk of recurrence, to survey for the development of second primary tumors, to deal with morbidity from treatment (i.e. speech and swallowing problems as well as wound care), to provide social and psychological support, and to deal with comorbidity not directly related to the cancer itself.

• Periodic examinations by the head and neck surgeon may be necessary during radiation therapy in patients experiencing difficulty with nutritional intake, airway or pain control.

• Periodic examinations by the radiation oncologist and a dentist in patients that received radiation therapy

• After all treatment is completed a general formula which is modified according to the individual patient's characteristics is:
  
  

  1st year post treatment:	1-3 months
  2nd year post treatment:	2-4 months
  3rd year post treatment:	3- 6 months
  4th and 5th years:	4- 6 months
  After 5 years:	Every 12 months

          These evaluations may require the use of an endoscope (flexible or rigid)

• MRI (to detect submucosal recurrence)
  
  

  Every 4 months	1st year
  Every 6 months	2nd year
  Yearly	Thereafter

• Chest radiographs, yearly.

• Liver enzymes, yearly.

• Thyroid function studies (TSH and free T4) should be monitored within the first year following completion of treatment. The thyroid function studies should be repeated according to findings on follow-up examinations.

• Epstein-Barr viral titers every six months for five years in those patients whose titers were elevated before therapy. (Optional)

• In the follow-up of nasopharyngeal cancer patients the physician should remain aware of the possibility of pituitary dysfunction. In the presence of any suggestive symptoms an appropriate evaluation should be initiated.

• Ophthalmological evaluation should be considered for those patients whose portals included the orbit or optic nerves/chiasm.

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VI.BIBLIOGRAPHY:

Fee WE, Gilmer PA, Goffinet DR. Surgical management of recurrent nasopharyngeal carcinoma after radiation failure at the primary site. Laryngoscope 98:1220-1226, 1988.

Shanmugaratnam K, Path FRC, Sobin LH. The World Health Organization histological classification of tumors of the upper respiratory tract and ear. A commentary on the second edition. Cancer 71:2689-2697, 1993.

Snyderman CH, Carrau RL, deVries EJ. Carotid artery resection: Update on preoperative evaluation (Chapter 27). In: Johnson JT, Derkay CS, Mandell-Brown MK, Newman RK. (eds), Instructional Courses (vol. 6), Mosby, St. Louis, 1993, pp. 341-346.

Fandi A, Altun N, Azli N, Armand JP, Cvitkovic. Nasopharyngeal cancer: Epidemiology, staging, and treatment. Seminars in Oncology 21:382-397, 1994.

Snyderman CH, Carrau RL. Commentary on article "Resection of Persistent Nasopharyngeal Carcinoma" (authors: Yumoto E, Gyo K, Yanagihara N. Skull Base Surg 4:59-64, 1994). Otolaryngology Journal Club Journal 2:56-58, 1995. 

Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV (>or=N2, MO) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. International Nasopharynx Cancer Study Group, VUMCAI trial. Institute Gustave Roussy, Rue Camille Desmouline, Villejuif, France. Int J Radiat Oncol Biol Phys 35(3):463-469, 1996.

Sanguineti G, Geara FB, Garden AS, Tucker SL, Ang KK, Morrison WH, Peters LJ. Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of local and regional control. Int J Radiat Oncol Biol Phys 35 (5):985-986, 1997.

Hsu MM, Ko JY, Sheen TS, Chang YL. Salvage surgery for recurrent nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg 123 (3):305-309, 1997.

Marks JE, Phillips JL, Menck HR. The national cancer data base report on the relationship of race and national origin to the histology of nasopharyngeal carcinoma. Cancer 83(3):582-588, 1998.