Nasopharyngeal Cancer

WHAT IS NASOPHARYNGEAL CANCER?
The nasopharynx has a cuboidal shape. The lateral walls are formed by the eustachian tube and the fossa of Rosenmuller. The roof, sloping downward from anterior to posterior, is bordered by the pharyngeal hypophysis, pharyngeal tonsil, and pharyngeal bursa with the base of the skull above. Anteriorly, the nasopharynx abuts the posterior choanae and nasal cavity, and the posterior boundary is formed by the muscles of the posterior pharyngeal wall. Inferiorly, the nasopharynx ends at an imaginary horizontal line formed by the upper surface of the soft palate and the posterior pharyngeal wall.

Nasopharyngeal cancer is a disease in which malignant (cancer) cells form in the tissues of the nasopharynx.



WHAT ARE THE RISK FACTORS OF NASOPHARYNGEAL CANCER?
Risk factors may include the following:

Chinese or Asian ancestry.
Exposure to the Epstein-Barr virus: The Epstein-Barr virus has been associated with certain cancers, including nasopharyngeal cancer and some lymphomas.
Unlike other squamous cell cancers of the head and neck, nasopharyngeal cancer does not appear to be linked to excess use of tobacco and alcohol. Factors thought to predispose to this tumor include Chinese (or Asian) ancestry, Epstein-Barr virus (EBV) exposure, and as yet unknown factors that result in very rare familial clusters.



HOW TO DETECT NASOPHARYNGEAL CANCER?

Possible signs of nasopharyngeal cancer include trouble breathing, speaking, or hearing.

The following symptoms suggest the possibility of nasopharyngeal cancer:

A lump in the nose or neck.
A sore throat.
Trouble breathing or speaking.
Nosebleeds.
Trouble hearing.
Pain or ringing in the ear.
Headaches.
The following tests that examine the nose and throat are used to diagnose nasopharyngeal cancer.

Physical exam of the throat: An exam is performed to detect if there are swollen lymph nodes in the neck and looks down the throat with a small, long-handled mirror to check for abnormal areas.
Nasoscopy: A procedure to look inside the nose for abnormal areas. A nasoscope (a thin, lighted tube) is inserted through the nose. Tissue samples may be taken for biopsy.
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.
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.
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: The removal of cells or tissues so they can be viewed under a microscope to check for signs of cancer.
Staging of nasopharyngeal cancer

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define nasopharyngeal cancer.

TNM definitions
Primary tumor (T)

TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor confined to the nasopharynx
T2: Tumor extends to soft tissues
T2a: Tumor extends to the oropharynx and/or nasal cavity without parapharyngeal extension*
T2b: Any tumor with parapharyngeal extension*
T3: Tumor invades bony structures and/or paranasal sinuses
T4: Tumor with intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hypopharynx, orbit, or masticator space
Parapharyngeal extension denotes posterolateral infiltration of tumor beyond the pharyngobasilar fascia.

Regional lymph nodes (N)

NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Unilateral metastasis in lymph node(s), ≤6 cm in greatest dimension, above the supraclavicular fossa*
N2: Bilateral metastasis in lymph node(s), ≤6 cm in greatest dimension, above the supraclavicular fossa*
N3: Metastasis in a lymph node(s)* >6 cm and/or to supraclavicular fossa
N3a: >6 cm
N3b: Extension to the supraclavicular fossa**
*Midline nodes are considered ipsilateral nodes.

**Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma and is the triangular region originally described by Ho. It is defined by 3 points: (1) the superior margin of the sternal end of the clavicle, (2) the superior margin of the lateral end of the clavicle, and (3) the point where the neck meets the shoulder. Note that this would include caudal portions of Levels IV and V. All cases with lymph nodes (whole or part) in the fossa are considered N3b.

Distant metastasis (M)

MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
AJCC stage groupings
Stage 0
Tis, N0, M0
Stage I
T1, N0, M0
Stage IIA
T2a, N0, M0
Stage IIB
T1, N1, M0
T2, N1, M0
T2a, N1, M0
T2b, N0, M0
T2b, N1, M0
Stage III
T1, N2, M0
T2a, N2, M0
T2b, N2, M0
T3, N0, M0
T3, N1, M0
T3, N2, M0
Stage IVA
T4, N0, M0
T4, N1, M0
T4, N2, M0
Stage IVB
Any T, N3, M0
Stage IVC
Any T, any N, M1


HOW TO TREAT NASOPHARYNGEAL CANCER?

High-dose radiation therapy is the primary treatment of nasopharyngeal cancer, both for the primary tumor site and the neck. Surgery, when feasible, is usually reserved for nodes that fail to regress after radiation or for nodes that reappear following clinical complete response. Radiation therapy dose and field margins are individually tailored to the location and size of the primary tumor and lymph nodes. Although most tumors are treated with external-beam irradiation exclusively, in some tumors radiation therapy may be boosted with intracavitary or interstitial implants or by the use of stereotactic radiosurgery when clinical expertise is available and the anatomy is suitable. A review of published clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible.

Accumulating evidence has demonstrated a high incidence (>30%-40%) of hypothyroidism in patients who have received radiation that delivered external-beam irradiation to the entire thyroid gland or to the pituitary gland. Thyroid-function testing of patients should be considered prior to therapy and as part of posttreatment follow-up.

Stage I Nasopharyngeal Cancer

Standard treatment options:

High-dose radiation therapy to the primary tumor site and prophylactic radiation therapy to the nodal drainage.
Stage II Nasopharyngeal Cancer
Standard treatment options:

Chemoradiotherapy.
High-dose radiation therapy to the primary tumor site and prophylactic radiation therapy to the nodal drainage.
Stage III Nasopharyngeal Cancer
Standard treatment options:

Chemoradiotherapy.
High-dose or superfractionated radiation therapy to the primary tumor site and bilateral neck nodes that are clinically positive.
Neck dissection may be indicated for persistent or recurrent nodes if the primary tumor site is controlled.
Treatment options under clinical evaluation:

Neoadjuvant chemotherapy as given in clinical trials has been used to shrink tumors, thereby rendering them more definitively treatable with radiation. Chemotherapy is given prior to the other modalities, hence the designation neoadjuvant to distinguish it from standard adjuvant therapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used in neoadjuvant chemotherapy. Two randomized prospective trials compared combination chemotherapy (cisplatin, epirubicin, and bleomycin or cisplatin plus fluorouracil [5-FU] injections) plus radiation therapy to radiation therapy alone. Although disease-free survival was improved in the chemotherapy group for both groups, improvement in overall survival was reported only from the intergroup.
Stage IV Nasopharyngeal Cancer
Standard treatment options:

Chemoradiotherapy.
High-dose or superfractionated radiation therapy to the primary tumor site and bilateral lymph nodes that are clinically positive.
Neck dissection should be reserved for persistent or recurrent nodes.
Chemotherapy for patients with stage IVC disease.
Treatment options under clinical evaluation:

Neoadjuvant chemotherapy as given in clinical trials has been used to shrink tumors, thereby rendering them more definitively treatable with radiation. Chemotherapy is given prior to the other modalities, hence the designation neoadjuvant to distinguish it from standard adjuvant therapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used in neoadjuvant chemotherapy. Two randomized prospective trials compared combination chemotherapy (cisplatin, epirubicin, and bleomycin or cisplatin plus fluorouracil [5-FU] injections) plus radiation therapy to radiation therapy alone. Although disease-free survival was improved in the chemotherapy group for both groups, improvement in overall survival was reported only from the intergroup.
Recurrent Nasopharyngeal Cancer

Standard treatment options:

Selected patients may be re-treated with moderate-dose external-beam radiation therapy using limited ports and an intracavitary or interstitial irradiation boost to the site of recurrence.
In highly selected patients, surgical resection of recurrent lesions may be considered.
If a patient has metastatic disease or local recurrence that is no longer amenable to surgery or radiation, chemotherapy should be considered.
HOW TO ESTIMATE THE PROGNOSIS OF NASOPHARYNGEAL CANCER?

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) depends 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.


Major prognostic factors adversely influencing outcome of treatment include large size of the tumor, higher T stage, and the presence of involved neck nodes. Other factors linked to diminished survival that were present in some, but not all, studies include age, nonlymphoepithelial histology, long interval between biopsy and initiation of radiation therapy, diminished immune function at diagnosis, incomplete excision of involved neck nodes, pregnancy during treatment, locoregional relapse, and certain EBV antibody titer patterns.

Small cancers of the nasopharynx are highly curable by radiation therapy, with survival rates of 80% to 90%.

Moderately advanced lesions without clinical evidence of spread to cervical lymph nodes are often curable, with survival rates of 50% to 70%.

Patients with advanced lesions, especially those associated with clinically positive cervical lymph nodes, cranial nerve involvement, and bone destruction, are poorly controlled locally by radiation therapy with or without surgery and often develop distant metastases despite local control.

Although most recurrences occur within 5 years of diagnosis, relapse can be seen at longer intervals. The incidence of second primary malignancies appears less than other head and neck sites.

Follow-up for patients includes routine periodic examination of the original tumor site and neck, chest x-ray, MRI or CT scan, and blood work. Monitoring of patients should include surveillance of thyroid and pituitary function; dental and oral hygiene; jaw exercises to avoid trismus; evaluation of cranial nerve function, especially those related to vision and hearing; and evaluation of systemic complaints to identify distant metastasis.

Poorly differentiated squamous cancer has been associated with EBV antibodies. High-titer antibodies to virus capsid antigen and early antigen, especially of high IgA class, or high titers that persist after therapy, have been associated with a poorer prognosis. This finding remains under evaluation.