Nasopharyngeal Cancer (pdq®) Treatment Health Professionals



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Nasopharyngeal Cancer (PDQ®) Treatment - Health Professionals

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Table of Contents
General Information

Cellular Classification

Stage Information

TNM definitions

AJCC stage groupings

Stage 0


Stage I

Stage IIA

Stage IIB

Stage III

Stage IVA

Stage IVB

Stage IVC

Treatment Option Overview

Stage I Nasopharyngeal Cancer

Stage II Nasopharyngeal Cancer

Stage III Nasopharyngeal Cancer

Stage IV Nasopharyngeal Cancer

Recurrent Nasopharyngeal Cancer

General Information

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 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 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.1
Symptoms and signs at presentation include painless, enlarged lymph nodes in the neck (present in approximately 75% of patients and often bilateral and posterior), nasal obstruction, epistaxis, diminished hearing, tinnitus, recurrent otitis media, cranial nerve dysfunction (usually II-VI or IX-XII), sore throat, and headache. 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.2
Tumors of many histologies can occur in the nasopharynx but this discussion, like the American Joint Committee on Cancer nasopharynx staging, refers exclusively to those of squamous cell type. Diagnosis is made by biopsy of the nasopharyngeal mass. Work-up includes careful visual examination (by mirror or endoscopic examination); documentation of the size and location of the tumor and neck nodes; evaluation of cranial nerve function and hearing; skull films (especially base of skull views), evaluating neural foramina; complete computed tomographic (CT) scan or magnetic resonance imaging (MRI) with views delineating the upper and lower extent of the lesion; chest x-ray; hemogram; and chemistry panel. 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 detecting abnormalities and in defining their extent.3-5
Major prognostic factors adversely influencing outcome of treatment include large size of the tumor, higher T stage, and the presence of involved neck nodes.6 Other factors linked to diminished survival 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, loco-regional 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%.7 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.8,9
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.10
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.2,11 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.

Cellular Classification

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 others varies substantially with histology. Subdivisions of squamous in this site include lymphoepithelioma (Schminke tumor); transitional cell tumors, well to poorly differentiated grade; and keratinizing or nonkeratinizing variety.1 The presence of keratin has been associated with reduced local control and survival.2,3



Stage Information

Staging systems are all clinical staging, 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 when possible and by both indirect mirror examination and direct endoscopy when necessary. 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.3,4 Information from diagnostic imaging studies may be used in staging. Magnetic resonance imaging offers an advantage over computed tomographic scanning in the detection and localization of head and neck tumors and the distinction of lymph nodes from blood vessels.5 If a patient has a relapse, a complete reassessment must be done to select the appropriate additional therapy.

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define nasopharyngeal cancer.6

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 of oropharynx and/or nasal fossa

T2a: without parapharyngeal extension

T2b: 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, or orbit

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 or less in greatest

dimension, above the supraclavicular fossa

N2: Bilateral metastasis in lymph node(s), 6 cm or less in greatest

dimension, above the supraclavicular fossa

N3: Metastasis in a lymph node(s)

N3a: greater than 6 cm in dimension

N3b: extension to the supraclavicular fossa



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


Results of radiation therapy for nasopharyngeal carcinoma (local-regional control and survival) are usually reported by T stage and N stage separately or by specific T and N subgroupings rather than by numerical stages I to IV. Outcome also depends on a variety of biologic and technical factors related to treatment.

Treatment Option Overview

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.1-4 Although most tumors are treated with external-beam irradiation exclusively, in some tumors radiation therapy may be boosted with radioactive intracavitary or interstitial implants when clinical expertise is available and the anatomy is suitable.5-8 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.9


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 post-treatment follow-up.10,11 The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.

Stage I Nasopharyngeal Cancer


Treatment options:

Standard: High-dose radiation therapy to the primary tumor site and prophylactic radiation therapy to the nodal drainage.1-3

Stage II Nasopharyngeal Cancer


Treatment options:

Standard:

1. Chemoradiotherapy.1[Level of evidence: 3iiiA]

2. High-dose radiation therapy to the primary tumor site and prophylactic radiation therapy to the nodal drainage.2-4

Stage III Nasopharyngeal Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)


Treatment options:

Standard:

1. Chemoradiotherapy.1,2

2. High-dose or superfractionated radiation therapy to the primary tumor site and bilateral neck nodes that are clinically positive.3-6

3. Neck dissection may be indicated for persistent or recurrent nodes if the primary tumor site is controlled.5



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 5-FU injections) plus radiation therapy to radiation therapy alone.1[Level of evidence: 1iiA];7[Level of evidence: 1iiDi] Although disease-free survival was improved in the chemotherapy group for both groups, improvement in overall survival was reported only from the intergroup.1 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.8-11 References:



Stage IV Nasopharyngeal Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)


Treatment options:

Standard:

1. Chemoradiotherapy.1,2

2. High-dose or superfractionated radiation therapy to the primary tumor site and bilateral lymph nodes that are clinically positive.3-6

3. Neck dissection should be reserved for persistent or recurrent nodes.5

4. Chemotherapy for patients with stage IVC disease.
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 5-FU injections) plus radiation therapy to radiation therapy alone.1[Level of evidence: 1iiA];7[Level of evidence: 1iiDi] Although disease-free survival was improved in the chemotherapy group for both groups, improvement in overall survival was reported only from the intergroup.1 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.8-11



Recurrent Nasopharyngeal Cancer


Treatment options:

Standard:

1. 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.1-4

2. In highly selected patients, surgical resection of recurrent lesions may be considered.

3. If a patient has metastatic disease or local recurrence that is no longer amenable to surgery or radiation, chemotherapy should be considered.5,6


Under clinical evaluation:

Clinical trials such as those evaluating chemotherapy and interferon should be considered.7







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