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6.8 Nasopharynx

​Updated: May 2003

General Information

The majority of tumors are carcinomas. 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

Patient Assessment

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

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.

Treatment

Radiotherapy

Radiotherapy is the primary treatment modality for carcinoma of the nasopharynx. The precise volume to be irradiated will be defined for each patient. In general it will consist of the tumor with a margin, involved lymph nodes and lymph nodes at risk of disease. The nasopharynx is a midline structure and there is a high incidence of bilateral nodal involvement hence both sides of the neck are usually irradiated. Because of the juxtaposition of the tumor volume to a number of critical number structures (optic nerve, chiasm, temporal lobe, brain stem, spinal cord etc), meticulous treatment planning is essential. The tumor and nodal chains are irradiated en-bloc usually through opposed lateral fields although the precise field arrangement will depend on the configuration of disease. A shrinking field is used and shielding is introduced so that the dose to critical structures dose not exceed organ tolerance.

Reference:

  1. Lee et al Nasopharyngeal carcinoma: Local control by megavoltage irradiation.The British Journal of Radiology 1993;66:528-536.

There is no evidence to support the use of altered fractionation schemes (accelerated/hyperfractionated radiotherapy) outside a randomized trial.

Escalation in dose with the use of either stereotactic radiotherapy or brachytherapy is not recommended routinely but may be considered in selected instances.

Chemotherapy

Nasopharyngeal cancer is much more sensitive to chemotherapy than other cancers arising in the upper aerodigestive tract. It has been used in a number of settings. These will be discussed individually below.

Neoadjuvant (prior to definitive treatment)

There have been several Phase 2/3 studies evaluating chemotherapy given prior to and/or following radiotherapy The majority of the regimes were cisplatinin based. Other active agents include 5-flurouracil,bleomycin, cyclophosphamide and adriamycin. In general these have shown increased toxicity, encouraging response rates but no increase in overall survival. this is not a recommended standard treatment at this time.

Concurrent/Adjuvant

A randomized trial comparing radiotherapy alone versus radiotherapy and concurrent cisplatin followed by adjuvant cisplatin/5-FU demonstrated in increase in 3 year relapse-free survival (24% versus 69%) and overall survival at 3 years (47% versus78%). The radiotherapy (70 Gy in 35 fractions) was identical in both arms. These differences are significant. Concerns expressed about this study include the poor results in the radiotherapy alone arm and the high proportion of patients with type 1 (well differentiated squamous cell carcinoma) who are not well represented in populations where this disease is endemic. In addition the treatment delivery was limited /problematic in the patients in the combined arm. In the light of these concerns this treatment strategy has not as yet been adopted as a standard at BCCA. The BCCA is currently participating in a multicenter international trial in an effort to evaluate this treatment strategy further.

Reference:

  1. Al-Sarraf M et al. Chemo-radiotherapy versus radiotherapy in patients with advanced nasopharyngeal carcer: phase III randomized intergroup study 0099 .Journal of Clinical Oncology 1998;16:1310-1317

Adjuvant (following definitive treatment).

This has not been widely studied. One randomized trial using non-cisplatin based therapy did not show any benefit.

Reference:

  1. Rossi et al Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer:results of a 4-year multicenter randomized study. Journal of Clinical Oncology 1988;61401-1410.

Chemotherapy for metastatic disease

There have been several phase 2 studies employing a variety of active agents (cisplatin, bleomycin,methotrexate, 5-flurouracil, gemcitabine) encouraging response rates are encountered. Median survival is between 10 = 16 months. Occasional long-term survivors are encountered.

References:

  1. Siu et al PhaseI/II study of the CAPABLE regimen for patients with poorly differentiated carcinoma of the nasopharynx. Journal of Clinical Oncology 1998;16:2514-2522.

  2. Boussen et al chemotherapy of Metastatic and/or recurrent Undifferentiated nasopharyngeal Carcinoma with Cispaltin,bleomycin and Fluorouracil. Journal of Clical oncology 1991;9:1675-1681.

Treatment of recurrence

Patients with local recurrence should be considered for salvage radiotherapy which may be curative. This may take the form of a gold seed implant or repeat external beam radiotherapy. Patients with a regional nodal recurrence should be considered for a neck dissection.

Reference:

  1. A Lee et al Retrospective analysis of patients with nasopharyngeal carcinoma treated during 1976-1985:survival after local recurrence. IJORP;1993:773-782.

SOURCE: 6.8 Nasopharynx ( )
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