IDENTITY Name Address Age Marital Status : Mr.

Y : Cibadak : 60 yr : Married

Main complain

: Fullness in the ear since 2 week ago

History of present illness : A 60-year-old man complained of a feeling of fullness in the ear, such as ringing. This perceived grievances already 2 weeks and is accompanied by hearing loss in his right ear. Patients also complain frequently experience recurring nosebleeds for no apparent reason. Patients are also said to feel a lump in his right neck the greater since a month ago.

History of past illness : Patients had never had complaints like this before. No history of DM, no history of hypertension.

Psychosocial History : The patient was a heavy smoker since the age of 20 years. In one day he could smoke up to two packs of clove cigarettes.

Physical Examination Ear : External ear : No deformities External acoustic canal : Right : Cerumen (-), discharge (-), laceration(-) Left : Cerumen (-), discharge (-), laceration(-)

Tympanic membrane : Right : intact, cone of light (+) Left : intact, cone of light (+) : Normal both side

Retroauricular Nose : External nose Mucous

: no deformity, normal shape : normal

 Nasal septum Choncha inferior

: No deviation : eutrophy both side, no discharge

Nasopharynx, Oropharynx : Uvula at the middle, arcus pharynx symmetric Mucous : normal mass at the posterior mucosa, diameter 1,5cm, firm border, redbrownies color Tonsil : T1/T1

Face : No Deviation Neck: Lymph nodes enlargement (+), diameter 4 cm, above supraclavicular fossa, firm border.

Working Diagnosis :

Suspect Nasopharyngeal carcinoma stadium IIB (T1 N1 M0)

Further examination : Complete Blood Test (Hb, Ht, Trombosit, Leukosit, LED) Serologi : SGOT anti SGPT anti VCA for EBV infection Chest X-ray CT scan head and neck Nasopharynx biopsy

Therapy : Chemoradiotherapy three cycles of cisplatin (100 mg/m2) during radiation three cycles of cisplatin (80 mg/m2) and 5-FU (1000 mg/m2) after the completion of radiation

NASOPHARYNGEAL CARCINOMA
INTRODUCTION Nasopharyngeal cancer develops in the nasopharynx, an area in the back of the nose toward the base of skull. To understand nasopharyngeal cancer, it helps to know about the structure and function of the nasopharynx. Nasopharyngeal cancer (NPC) or more commonly known as nose cancer is a disease in which cancer cells develop from the tissues of the nasopharynx. Normal cells grow, divide and replace themselves in an orderly manner. Your body relies on this orderly activity to repair injuries and replace worn-out tissue. Cancer develops when these cells divide too rapidly and grow without control. Too much tissue is produced and a tumour begins to form. This tumour can be malignant (cancerous) or benign (non-cancerous). Although more common in many Asian countries, malignancy of the nasopharynx is a relatively rare disease in the United States. It is often misdiagnosed early because of vague presenting symptoms and the difficulty of examination of the nasopharynx. There are several different types of malignancy known to occur in the nasopharynx including squamous cell carcinoma, lymphoma, salivary gland malignancy, and sarcomas. By far the most common are the squamous cell carcino

mas which can be divided into three types and are often collectively called nasopharyngeal carcinoma. These lesions will be the focus of this grand rounds.

ANATOMY

The nasopharynx serves as a passageway for air from the nose to the throat (and eventually to the lungs). The nasopharynx communicates with the nasal cavity anteriorly at the choanae and with the oropharynx inferiorly at the lower border of the soft palate. Superiorly and posteriorly, important bony landmarks include the skull base and the upper vertebral bodies. The eustachian tubes enter the nasopharynx laterally and are covered superiorly and posteriorly by cartilage known as the torus tubarius. The fossa of Rosenmuller (lateral nasopharyngeal recess) is located superior and posterior to the torus and is the most common location for nasopharyngeal carcinoma. Many of the skull base foramen that carry important neural and vascular structures are located immediately adjacent to the nasopharynx. The nasopharynx is lined by mucosa that is covered with either stratified squamous epithelium or pseudostratified columnar epithelium. It is from this epithelium that nasopharyngeal carcinoma arises. The mucosa also contains other structures including salivary and lymphoid tissue. As mentioned above, these elements can also give rise to malignancy although much less frequently.

EPIDEMIOLOGY Nasopharyngeal carcinoma may occur at any age and as presented above, occurs much more frequently in the Chinese population (18% verses 0.25% in North America).1 It has been noted that the rate of nasopharyngeal carcinoma rises as Chinese genes are introduced into an area. Also a first generation Chinese-American will have a reduced risk of developing this lesion but it remains higher than the overall U.S. rate. These findings seem to indicate both genetic and environmental etiologies. HLA-A2 and HLA-B-Sin 2 histocompatibility loci have been identified as possible markers for genetic susceptibility.(1) Another important etiology in some types of nasopharyngeal carcinoma is the Epstein-Barr virus. Evidence of the virus has been found in the tumor cells themselves and, as will be discussed later, many patients have anti-EBV antibodies. Other possible etiologies include exposure to nitrosamines, polycyclic hydrocarbons, chronic nasal infection, poor hygiene, and poor ventilation of the nasopharynx.(1)

Mortality/Morbidity When radiotherapy is used alone, survival rates range from 40-50%. Use of combination radiation therapy and chemotherapy allows long-term survival rates of 55-80%. Sex A male preponderance is observed. The male-to-female ratio is approximately 2:1. Age Nasopharyngeal carcinoma has a bimodal age distribution. A small peak is observed in late childhood, and a second peak occurs in people aged 50-60 years. Childhood nasopharyngeal carcinoma is usually a disease of adolescence.[3]

PATHOPHYSIOLOGY The detection of the Epstein-Barr virus (EBV) nuclear antigen and viral DNA in nasopharyngeal carcinoma has revealed that EBV can infect epithelial cells and is associated with their malignant transformation.[1] EBV genome has been found in cells of preinvasive lesions, suggesting that it is directly related to the process of transformation.

CLASSIFICATION The World Health Organization has developed a classification system that divides nasopharyngeal carcinomas into three types based on light microscopy findings. Type I or Squamous cell carcinomas are characterized by moderate to well differentiated cells that produce keratin and have intercellular bridges and other findings similar to typical squamous cell carcinomas. Twenty-five percent of nasopharyngeal carcinomas are of this type. Type II lesions, non-keratinizing carcinomas, have cells that vary from mature to anaplastic in appearance but produce minimal if any keratin. These carcinomas often resemble transitional cell carcinoma of the bladder. Approximately twelve percent of nasopharyngeal carcinomas are of this type. Type III comprises a diverse group of carcinomas often described as undifferentiated carcinomas. Included in this group are lymphoepitheliomas, anaplastic, clear cell, and spindle cell variants. These lesions are often difficult to differentiate from lymphoma and may require special stains and markers to identify their epithelial origin. The tumor cells are often located in a lymphoid stroma and when the density of the stroma is greater than the tumor cells themselves, the lesion is termed a lymphoepithelioma.(2) Sixty percent of all nasopharyngeal carcinomas and nearly all of those found in young patients are of this type. Although type I lesions are often called squamous cell carcinomas, it must be remembered that all three types arise from nasopharyngeal epithelial cells and can be identified as squamous cell carcinomas by electron microscopy. There are however certain important differences between type I lesions and types II and III. The 5 year survival for type I carcinomas is only 10% whereas types II and III have approximately 50% survival at five years. However, types II and III tend to be more chronic diseases with recurrences sometimes occurring many years after initial treatment. Another important difference is that types II and III are more commonly associated with anti-EBV serologies and EBV DNA in the tumor cells. Human papillomavirus (types 11 and 16) DNA has been identified in WHO type I carcinomas.(3)

CLINICAL COURSE SIGNS AND SYMPTOMS TO REPORT TO YOUR DOCTOR: A sore throat that does not go away Hoarseness of voice, difficulty in swallowing Difficulty breathing or speaking Hearing problems a change or loss in hearing, ringing in the ear. As mentioned above the symptoms of nasopharyngeal carcinoma are often subtle initially and a high index of suspicion is required for early diagnosis. Unilateral hearing loss from a middle ear effusion is the most common finding and should be considered an indication for nasopharyngeal exam. Ear ache or discharge from the ear Frequent headaches Nasal obstruction or stuffiness. Large or exophytic lesions may cause nasal obstruction or epistaxis. One or more lumps in the nose or on the neck. Another common presenting complaint is a neck mass resulting from regional spread. The doctor feels for swollen lymph nodes in the neck and looks down the throat with a small, long-handled mirror to check for abnormal areas. Examination of the nasopharynx may reveal an exophytic mass or a smooth, mucosal covered mass. The most common initial location for these lesions is in the fossa of Rosenmuller. The nasopharynx may also be essentially normal in appearance with the diagnosis only made after random biopsy for regional spread without a known primary. The nasopharynx has a rich lymphatic network that communicates across the midline making bilateral regional spread a common finding. Distant spread to the lungs, bones or liver is possible but rare in North American patients (< 3% at presentation).(1) Frequent nosebleeds Bloodstained sputum Fatigue Weight loss of unknown reason

Other conditions may cause the same symptoms and do not always mean cancer. Also, as the tumor enlarges, adjacent cranial nerves may become involved. Xerophthalmia may result from involvement of the greater superficial petrosal

nerve at the foramen lacerum and facial pain may indicate Trigeminal nerve involvement. Diplopia may occur with isolated Abducens nerve injury whereas ophthalmoplegia indicates involvement of cranial nerves III, IV and VI, usually in the cavernous sinus or the superior orbital fissure. Horner's syndrome occurs with injury to the cervical sympathetic chain and more extensive skull base involvement produces deficits of the lower cranial nerves (IX, X, XI, XII).(4)

PATTERNS OF LYMPH NODE METASTASIS

The regional lymphatic drainage of the neck is divided into seven levels. The levels allow for a standardized format for radiologists, surgeons, pathologists, and radiation oncologists to communicate concerning specific sites within then neck and does not represent regions isolated by fascial planes. The levels are defined as the following: Level I the submental and submandibular nodes Level Ia the submental nodes; medial to the anterior belly of the digastric muscle bilaterally, symphysis of mandible superiorly, and hyoid inferiorly Level Ib the submandibular nodes and gland; posterior to the anterior belly of digastric, anterior to the posterior belly of digastric and inferior to the body of the mandible Level II upper jugular chain nodes Level IIa jugulodigastric nodes; deep to sternocleidomastoid (SCM), anterior to the posterior border of the muscle, posterior to the posterior aspect of the posterior belly of digastric, superior to the level of the hyoid, inferior to spinal accessory nerve (CN XI) Level IIb submuscular recess; superior to spinal accessory nerve to the level of the skull base Level III middle jugular chain nodes; inferior to the hyoid, superior to the level of the hyoid, deep to SCM from posterior border of the muscle to the strap muscles medially

Level IV lower jugular chain nodes; inferior to the level of the cricoid, superior to the clavicle, deep to SCM from posterior border of the muscle to the strap muscles medially

Level V posterior triangle nodes Level Va lateral to the posterior aspect of the SCM, inferior and medial to splenius capitis and trapezius, superior to the spinal accessory nerve Level Vb lateral to the posterior aspect of SCM, medial to trapezius, inferior to the spinal accessory nerve, superior to the clavicle Level VI anterior compartment nodes; inferior to the hyoid, superior to suprasternal notch, medial to the lateral extent of the strap muscles bilaterally

Level VII paratracheal nodes; inferior to the suprasternal notch in the upper mediastinum.

Patterns of spread from primary tumor sites in the head and neck to cervical lymphatics are well described. The location and incidence of metastasis vary according to the primary site. Primary tumors within the oral cavity and lip metastasize to the nodes in Levels I, II, and III. The occurrence of skip metastases with oral tongue lesions makes possible the involvement of nodes in Level III or IV without involvement of higher echelon nodes. Tumors arising in the oropharynx, hypopharynx, and larynx most commonly spread to the lymph nodes in Levels II, III, and IV. Isolated Level V nodes are uncommon with oral cavity, pharyngeal and laryngeal primaries, however, Level V adenopathy may be seen with concomitant involvement of higher echelon nodes. Malignancies of the nasopharynx and thyroid commonly spread to posterior lymph nodes in addition to the jugular chain nodes.

Levels of the neck denoting lymph node bearing regions.

PATIENT ASSESSMENT The assessment of the tumor and regional lymph nodes is based on physical examination, endoscopy and appropriate radiological investigation.

Nasoscopy: A procedure to look inside the nose for abnormal areas. A nasoscope is inserted through the nose. A nasoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.

Neurological exam: A series of questions and tests to check the brain, spinal cord, and nerve function. The exam checks a person's mental status, coordination, and ability to walk normally, and how well the muscles, senses, and reflexes work. This may also be called a neuro exam or a neurologic exam.

Head and chest x-rays: An x-ray of the skull and organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside

the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).

CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of

radioactiveglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do. PET scans may be used to find nasopharyngeal cancers that have spread to the bone.

Laboratory tests: Medical procedures that test samples of tissue, blood, urine, or other substances in the body. These tests help to diagnose disease, plan and check treatment, or monitor the disease over time.

Biopsy: is taking a sample of abnormal tissue for examination under microscope to help in diagnosing the disease. This can be done during nasendoscopy.The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. Imaging of the nasopharynx and its environs is best carried out with either CT

scan and/or an MRI. In both cases axial and coronal images are required for optimal evaluation. CT is better for determining the presence or absence of bone invasion. MRI is particularly helpful in differentiating between inflammatory change and tumor and for evaluating intracranial extension. Other radiological investigations include a chest X-ray, liver ultrasound if liver function tests are abnormal or there is advanced nodal disease and, a bone scan if there is bone pain, elevation of alkaline phosphatase or advanced nodal disease. Other imaging modalities such as PET may be cost effective in detecting systemic metastatic disease for those at high risk.

RADIOLOGICAL AND LABORATORY EVALUATION Contrast CT with bone and soft tissue windows is the imaging tool of choice for determining the extent of spread of nasopharyngeal carcinoma. MRI may also be helpful in the evaluation of soft tissue involvement, especially with recurrent carcinomas. A chest x-ray is usually included in the initial work-up to rule out pulmonary metastasis. Chest CT, including the liver, and bone scans may be indicated if distant spread is suspected. Routine CBC, chemistry profiles and liver function test are obtained to screen for metastatic disease. Additionally, several anti-EBV serologic test are useful in detecting and determining the prognosis of nasopharyngeal carcinoma, particularly types II and III. Immunofluorescence for IgA antibodies to the viral capsid antigen (VCA) and IgG antibodies to the early antigen (EA) can help identify occult or early disease in many cases. As these tests become more practical and widely available, they may be used to screen for nasopharyngeal carcinoma in high incidence areas. Another serologic test that provides prognostic information is the antibody- dependent cellular cytotoxicity (ADCC) assay. High titers of this antibody are related to better long-term survival.

STAGING The process used to find out whether cancer has spread within the nasopharynx or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The results of the tests used to diagnose nasopharyngeal cancer are often also used to stage the disease. Several staging methods have been developed for nasopharyngeal carcinoma including that of the American Joint Committee for Cancer Staging, International Union Against Cancer, and the Ho system.(1) Unfortunately, many of these systems fail to consider important prognostic indicators peculiar to nasopharyngeal carcinoma and often have a similar prognosis for different stages. Neel and Taylor developed a system based on five important prognostic indicators that provides a clearer separation between stages. This system assigns a numeric value to the presence or absence of the indicator and the stage is determined from the total score. The prognostic indicators considered and the associated value

include extensive primary tumor (+0.5), duration of symptoms prior to diagnosis less than 2 months (-0.5), presence of seven or more symptoms (+1), histologic WHO type I (+1), and lower cervical node disease (+1). Stage A is present if the score is less than zero, stage B if 0-0.99, stage C if 1.0-1.99 and stage D if greater than 2.0.5 As mentioned above, the ADCC assay titer is important and may be considered if available. Classical Nasopharyngeal carcinoma has been classified into three types by the WHO: Type 1 Keratinizing squamous cell carcinoma Type 2 Nonkeratinizing /poorly differentiated carcinoma Type 3 Undifferentiated/anaplastic carcinoma. Type 1 may have an association with cigarette and alcohol consumption and accounts for up to 30% of cases in non-endemic areas and < 5% in endemic areas. Other less common tumor types include minor salivary gland tumors, sarcomas, lymphomas, plasmocytomas and angiofibromas.The management of these tumors is individualized. Common presenting symptoms include unilateral hearing loss, a mass in the neck, nasal stuffiness/bleeding, headache and cranial nerve palsies. Nasopharyngeal carcinoma may spread by direct extension into neighboring structures. Superior spread into the foramen lacerum or foramen ovale often results damage to cranial nerves VI, V and occasionally III. Postero-lateral spread into the parapharyngeal space is common and may lead to lower cranial nerve palsies. The nasopharynx has a rich supply of lymphatics and lymph node metastases are common at presentation. Nodes that are commonly involved include the jugulodigastric, the posterior cervical and retropharyngeal lymph nodes. Systemic dissemination (15 20%) is more common at presentation than other head and neck cancers. It is more common when there is extensive nodal disease and consideration should be given to a metastatic workup at presentation if there is a high index of suspicion of distant disease.

The staging system employed is the UICC 1997 System. Nasopharynx (T) T1 Tumour confined to the nasopharynx T2 Extension to the oropharynx or nasal cavity T2a without parpharyngeal extension T2b with parapharyngeal extension T3 Bone invasion and/or paranasal sinuses T4 Cranial nerve palsies, extension to the infratemporal fossa , intracranial extension etc

Lymph nodes (N) N1 Unilateral lymph node (s)< 6 cm above supraclavicular fossa N2 Bilateral lymph nodes < 6 cm above supraclavicular fossa N3 Unilateral or bilateral node(s) > 6 cm or nodes in the supraclavicular fossa

Distant Metastasis M0 No evidence of distant metastasis M1 Distant metastasis

The following stages are used for nasopharyngeal cancer: Stage 0 (Carcinoma in Situ) In stage 0, abnormal cells are found in the lining of the nasopharynx. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ. Stage I In stage I, cancer has formed and is found in the nasopharynx only. Stage II Stage II nasopharyngeal cancer is divided into stage IIA and stage IIB as follows:

Stage IIA: Cancer has spread from the nasopharynx to the oropharynx (the middle part of the throat that includes the soft palate, the base of the tongue, and the tonsils), and/or to the nasal cavity.

Stage IIB: Cancer is found in the nasopharynx and has spread to lymph nodes on one side of the neck, or has spread to the area surrounding the

nasopharynx and may have spread to lymph nodes on one side of the neck. The involved lymph nodes are 6 centimeters or smaller. Stage III In stage III nasopharyngeal cancer, the cancer:

is found in the nasopharynx and has spread to lymph nodes on both sides of the neck and the lymph nodes are 6 centimeters or smaller; or

has spread into the soft tissues (oropharynx and/or nasal cavity) and to lymph nodes on both sides of the neck and the lymph nodes are 6 centimeters or smaller; or

has spread beyond the soft tissues into areas around the pharynx and to lymph nodes on both sides of the neck and the lymph nodes are 6 centimeters or smaller; or

has spread to nearby bones or sinuses and may have spread to lymph nodes on one or both sides of the neck and the involved lymph nodes are 6 centimeters or smaller.

Stage IV Stage IV nasopharyngeal cancer is divided into stage IVA, stage IVB, and stage IVC as follows:

Stage IVA: Cancer has spread beyond the nasopharynx and may have spread to the cranial nerves, the hypopharynx (bottom part of the throat), areas in and around the side of the skull or jawbone, and/or the bone around the eye. Cancer may also have spread to lymph nodes on one or both sides of the neck, and the involved lymph nodes are 6 centimeters or smaller.

Stage IVB: Cancer has spread to lymph nodes above the collarbone and/or the involved lymph nodes are larger than 6 centimeters.

Stage IVC: Cancer has spread beyond nearby lymph nodes to other parts of the body.

Recurrent Nasopharyngeal Cancer Recurrent nasopharyngeal cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the nasopharynx or in other parts of the body.

MANAGEMENT There are different types of treatment for patients with nasopharyngeal cancer.Different types of treatment are available for patients with nasopharyngeal cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. Before starting treatment, patients may want to think about taking part in a clinical trial. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team. Three types of standard treatment are used: Radiation therapy Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy to the thyroid or the pituitary gland may change the way the thyroid gland works. The doctor may test the thyroid gland before and after therapy to make sure it is working properly. It is also important that a dentist check the patient's teeth, gums, and mouth, and fix any existing problems before radiation therapy begins.

Chemotherapy Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated. Chemotherapy as an adjuvant to radiation therapy has yet to demonstrate a significant improvement in long-term outcome and therefore continues to be used mainly as a palliative measure. While immunotherapy has also not shown any clear improvement in survival to date, the close association of certain anti-EBV antibodies with an improved prognosis offers the hope of effective immunologically based approach in the future. Also, a vaccine to protect against EBV related disease may one day be reality.

Surgery Surgery is a procedure to find out whether cancer is present, to remove cancer from the body, or to repair a body part. Also called an operation. Surgery is sometimes used for nasopharyngeal cancer that does not respond to radiation therapy. If cancer has spread to the lymph nodes, the doctor may remove lymph nodes and other tissues in the neck. Surgical management is primarily used to obtain tissue for histologic examination and for EBV testing. If an obvious tumor is present in the nasopharynx, biopsy under local anesthesia in the clinic may be practical if the patient is cooperative. Since these lesions are often heterogeneous, the biopsy must be large to ensure appropriate diagnosis and WHO typing. Instruments such as the Takahashi or Blakesley forceps are ideal for obtaining an adequate biopsy.(7) If the tumor is not obvious or if sufficient tissue cannot be obtained in clinic, the patient should be taken to the operative room for formal endoscopy and biopsy under general anesthesia.

Although surgical resection in this region was once considered impossible, modern approaches do allow access for excision. This is rarely indicated as a primary treatment but may be appropriate in certain cases of recurrent disease when additional radiation is not appropriate. The infratemporal fossa and transparotid temporal bone approaches offer access to the pterygomaxillary space and infratemporal fossa but have limited exposure of the nasopharynx, particularly the contralateral side. These lateral approaches also incur significant morbidity. The transpalatal approach is associated with less morbidity but also less lateral exposure. Other authors have reported success using transmaxillary and transmandibular approaches for residual/recurrent nasopharyngeal carcinoma.(8) A more common therapeutic surgical indication involves a successfully treated primary tumor with regional failure. A radical neck dissection may be an appropriate procedure in this case and has been reported as being more effective at controlling neck disease than additional radiation.(9) Finally, myringotomy with ventilation tube placement may be considered in a patient with persistent, symptomatic middle ear effusion. If indicated this should be performed prior to radiation therapy because the incidence of complications such as otorrhea and persistent otalgia are reduced. If considered after radiation therapy, a period of observation prior to the procedure is usually indicated and amplification may be a better option.(2)

Biologic therapy Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Intensity-modulated radiation therapy Intensity-modulated radiation therapy (IMRT) is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

The following factors are taken into account: location of the cancer extent of the disease any presence of cancer spread how far is the spread the general health of the patient age of the patient

Treatment Options by Stage Stage I Nasopharyngeal Cancer Treatment of stage I nasopharyngeal cancer is usually radiation therapy to the tumor and lymph nodes in the neck.

Stage II Nasopharyngeal Cancer Treatment of stage II nasopharyngeal cancer may include the following:

Chemotherapy combined with radiation therapy. Radiation therapy to the tumor and lymph nodes in the neck.

Stage III Nasopharyngeal Cancer Treatment of stage III nasopharyngeal cancer may include the following:

Chemotherapy combined with radiation therapy. Radiation therapy to the tumor and lymph nodes in the neck. Radiation therapy followed by surgery to remove cancer-containing lymph nodes in the neck that remain or come back after radiation therapy.

A clinical trial of chemotherapy before, combined with, or after radiation therapy.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

Check for clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III nasopharyngeal cancer.

Stage IV Nasopharyngeal Cancer Treatment of stage IV nasopharyngeal cancer may include the following:

Chemotherapy combined with radiation therapy. Radiation therapy to the tumor and lymph nodes in the neck. Radiation therapy followed by surgery to remove cancer-containing lymph nodes in the neck that remain or come back after radiation therapy.

Chemotherapy for cancer that has metastasized (spread) to other parts of the body.

A clinical trial of chemotherapy before, combined with, or after radiation therapy.

A clinical trial of new radiation therapy such as intensity-modulated radiation therapy.

This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site. Check for clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV nasopharyngeal cancer.

Treatment Options for Recurrent Nasopharyngeal Cancer Treatment of recurrent nasopharyngeal cancer may include the following:

External radiation therapy plus internal radiation therapy. Surgery. Chemotherapy. A clinical trial of biologic therapy and/or chemotherapy. External beam radiation therapy continues to be the mainstay of treatment for

this lesion. Doses of 6500 to 7000 cGy are directed at the primary lesion and the upper echelon lymph nodes. If clinically positive, lower cervical nodes are included in the field. Also, prophylactic treatment of clinically negative lower cervical nodes with 5000 cGy may be considered. Brachytherapy is occasionally used as an adjuvant to external beam radiation or in cases of recurrent/residual tumor.

Although

improved

methods

of

delivering

the

radiation

have

reduced

complications, well known side effects do occur. These may be especially problematic when reirradiation is required for residual or recurrent disease. In addition to the common finding of xerostomia, eustachian tube dysfunction often occurs. Early after treatment this manifest as middle ear effusion with associated hearing loss. Over time however, many patients eventually develop patulous eustachian tubes.(6) Endocrine disorders such as hypopituitarism, hypothyroidism, and hypothalamic dysfunction are possible long-term sequelae and periodic endocrine evaluations are appropriate. Trismus and other problems related to soft tissue fibrosis, as well as ophthamologic complications and base of skull necrosis, may occur.

The prognosis (chance of recovery) and treatment options depend on the following:

The stage of the cancer (whether it affects part of the nasopharynx, involves the whole nasopharynx, or has spread to other places in the body).

The type of nasopharyngeal cancer. The size of the tumor. The patient's age and general health.

CONCLUSION Nasopharyngeal carcinoma is a rare disease in North America and has an overall 5 year survival of 40% for all types. It is much more common in people of Chinese ancestry. The presenting signs and symptoms are often subtle requiring a high index of suspicion for early diagnosis. Three WHO classes are described with the first often being described as squamous cell carcinoma and carrying a worse prognosis. It should be remembered that all classes are derived from epithelial cells and can be identified as squamous cell carcinomas by electron microscopy. The second two classes confer better survival and are often associated with antiEBV antibodies. Treatment is primarily radiation therapy.

REFERENCES 1. Neel HB, Slavit DH. Nasopharyngeal Cancer. In: Bailey BJ ed. Head and Neck Surgery - Otolaryngology. Philadelphia: J.B. Lippincott, 1993:1257-73. 2. Wei WI, Sham JS. Cancer of the Nasopharynx. In: Myers EN, Suen JY eds. Cancer of the Head and Neck. Philadelphia: W.B. Saunders, 1996:277-93. 3. Hording U, Nielsen HW, Daugaard S, Albeck H. Human Papillomavirus types 11 and 16 detected in nasopharyngeal carcinomas by the polymerase chain reaction. Laryngoscope 1994;104:99-102. 4. Gustafson RO, Neel HB. Cysts and Tumors of the Nasopharynx. In: Paparella MM et al. eds. Otolaryngology. Philadelphia: W.B. Saunders, 1991:2189-98. 5. Neel HB, Taylor WF. New staging system for nasopharyngeal carcinoma long-term outcome. Arch Otol HNS 1989;115:1293-1303. 6. Young YH, Cheng PW, Ko JY. A 10-year longitudinal study of tubal function in patients with nasopharyngeal carcinoma after irradiation. Arch Otol HNS 1997;123:945-8. 7. Hasselt CA, John DG. Diagnosing nasopharyngeal cancer. Laryngoscope 1994;104:103-4. 8. Hsu MM, Ko JY, Sheen TS, Chang YL. Salvage surgery for recurrent nasopharyngeal carcinoma. Arch Otol HNS 1997;123:305-9. 9. Yen KL, et al. Salvage neck dissection for cervical recurrence of nasopharyngeal carcinoma. Arch Otol HNS 1997;123:725-9.