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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.
Unlike other squamous cell cancers of the head and neck, nasopharyngeal cancer does not appear to be linked to excess use of tobacco or moderate alcohol intake (up to 15 drinks a week). Factors thought to predispose to this tumor include the following:
Signs and Symptoms
Symptoms and signs at presentation include the following:
In the patient who presents with only cervical adenopathy, the finding of EBV genomic material in the tissue after amplification of DNA with the polymerase chain reaction lends strong evidence for a nasopharyngeal primary tumor, and a concerted search should be conducted in that area.
Diagnosis is made by biopsy of the nasopharyngeal mass. Workup includes the following:
Any clinical or laboratory suggestion of distant metastasis may prompt further evaluation of other sites. Careful dental and oral hygiene evaluation and therapy is particularly important prior to initiation of radiation treatment. MRI is often more helpful than CT scans in assessing skull base involvement and in defining the extent of abnormalities detected.[5,6,7]
Major prognostic factors adversely influencing outcome of treatment include the following:
Other factors linked to diminished survival that were present in some, but not all, studies include the following:
Small cancers of the nasopharynx are highly curable by radiation therapy, and patients with these small cancers have shown survival rates of 80% to 90%.
Moderately advanced lesions without clinical evidence of spread to cervical lymph nodes are often curable, and patients with these lesions have shown survival rates of 50% to 70%.
Follow-up for patients includes the following:
Monitoring of patients should include the following:
Although most recurrences occur within 5 years of diagnosis, relapse can be seen at longer intervals. The incidence of second primary malignancies is less than after treatment of tumors at other head and neck sites.
Poorly differentiated squamous cell cancer has been associated with EBV antibodies.[4,12] 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.
Tumors of many histologies can occur in the nasopharynx, but this discussion, like the American Joint Committee on Cancer nasopharynx staging, refers exclusively to WHO grade I-, II-, and III-type nasopharyngeal carcinoma.
Although a wide variety of malignant tumors may arise in the nasopharynx, only squamous cell carcinoma is considered in this discussion because management of the other types varies substantially with histology. Subdivisions of squamous cell carcinoma in this site include the following:
World Health Organization (WHO) histopathological grading system describes three types of nasopharyngeal cancer:
Previous subdivisions of nasopharyngeal carcinoma included lymphoepithelioma, which is now classified as WHO grade III characterized by lymphoid infiltrate.
WHO grade I-type cancer accounts for 20% of cases in United States and is associated with alcohol and tobacco use; WHO grade II and III represent the endemic form seen in Southern China.
The presence of keratin has been associated with reduced local control and survival.
Staging systems are all clinical staging and are based on the best possible estimate of the extent of disease before treatment.[1,2] Assessment of the primary tumor is based on inspection and palpation, and fiberoptic endoscopic evaluation. The tumor must be confirmed histologically, and any other pathologic data obtained on biopsy may be included. Evaluation of the function of the cranial nerves is especially appropriate for tumors of the nasopharynx. The appropriate nodal drainage areas are examined by careful palpation and radiologic evaluation. The retropharyngeal lymph nodes are the first echelon of drainage.[3,4] Information from diagnostic imaging studies may be used in staging. Magnetic resonance imaging provides additional information to computed tomographic scanning in the evaluation of skull base invasion and intracranial spread. Positron emission tomography scans combined with CT are helpful in radiation treatment planning for target delineation of the primary tumor, aids in detection of metastatic nodal involvement and metastatic spread such as lung or skeletal metastases in patients with advanced nasopharyngeal cancer.
If a patient has a relapse, a complete reassessment must be done to select the appropriate additional therapy.
Definitions of TNM
The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define nasopharyngeal cancer.
Standard treatments for patients with nasopharyngeal cancer include the following:
High-dose radiation therapy with chemotherapy is the primary treatment of nasopharyngeal cancer, both for the primary tumor site and the neck. When feasible, surgery is usually reserved for nodes that fail to regress after radiation therapy or for nodal recurrence 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.[2,3,4,5] Although most tumors are treated with external-beam radiation therapy (EBRT) 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.[6,7,8,9,10] Intensity-modulated radiation therapy (IMRT) results in a lower incidence of xerostomia and may provide a better quality of life than conventional three-dimensional or two-dimensional radiation therapy.[11,12][Level of evidence: 1iiC] Results of a phase II RTOG study (RTOG-0225) showed the feasibility of IMRT in a multi-institutional setting and minimal grade III and IV xerostomia rates. The rate of grade 2 xerostomia at 1 year from start of IMRT was 13.5%. Only 2 of 68 patients were reported with grade 3 xerostomia, and none had grade 4 xerostomia.[Level of evidence: 2C]
Accumulating evidence has demonstrated a high incidence (>30%–40%) of hypothyroidism in patients who have received radiation therapy that delivered EBRT 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.[14,15]
Treatments under clinical evaluation for patients with nasopharyngeal cancer include the following:
Information about ongoing clinical trials is available from the NCI Web site.
Standard treatment options:
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I nasopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II nasopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Treatment options under clinical evaluation:
Two randomized prospective trials compared combination chemotherapy (i.e., cisplatin, epirubicin, and bleomycin or cisplatin plus fluorouracil [5-FU] infusion) plus radiation therapy to radiation therapy alone.[Level of evidence: 1iiA];[Level of evidence: 1iiDii] Although disease-free survival was improved in the chemotherapy group for both groups, improvement in overall survival was reported only from the Intergroup trial in which chemotherapy with cisplatin was ever concurrently given.
Clinical trials for advanced tumors evaluating the use of chemotherapy before radiation therapy, concomitant with radiation therapy, or as adjuvant therapy after radiation therapy should be considered.[19,20,21,22]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III nasopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Clinical trials for advanced tumors to evaluate the use of chemotherapy before radiation therapy, concomitant with radiation therapy, or as adjuvant therapy after radiation therapy should be considered.[19,20,21,22]
A phase II, randomized study of 65 patients with stage III and IV nasopharyngeal carcinoma were randomly assigned to neoadjuvant docetaxel (75 mg/m2) and cisplatin (75 mg/m2) every 3 weeks for two cycles followed by cisplatin (40 mg/m2) every week versus chemoradiation alone. Rates of grade 3 or 4 neutropenia were 97% during the neoadjuvant arm with no difference in toxicities between the two groups during the chemoradiation portion of treatment. The 3-year progression-free survival for neoadjuvant docetaxel versus the control arm was 88.2% and 59.5% (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.20–1.19; P = .12). The 3-year overall survival for neoadjuvant docetaxel versus the control arm was 94.1% and 67.7% (HR, 0.24; 95% CI, 0.078–0.73; P = .012).[Level of evidence: 1iiDiii] These data have to be confirmed in a definitive phase III trial.
Three randomized, prospective trials compared combination chemotherapy (i.e., cisplatin, epirubicin, and bleomycin or cisplatin plus fluorouracil [5-FU] infusion) plus radiation therapy to radiation therapy alone.[Level of evidence: 1iiA];[24,25][Level of evidence: 1iiDii] Although disease-free survival (DFS) was improved in the chemotherapy group for both groups, improvement in overall survival (OS) was reported only from the Intergroup trial in which chemotherapy with cisplatin was ever concurrently given.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV nasopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent nasopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of nasopharyngeal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Nasopharyngeal Cancer Treatment are:
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Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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National Cancer Institute: PDQ® Nasopharyngeal Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/nasopharyngeal/HealthProfessional. Accessed <MM/DD/YYYY>.
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Last Revised: 2012-10-12
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