Nasopharynx  

Eighty-five to ninety percent of malignant nasopharyngeal tumors are epidermoid or undifferentiated carcinoma. Lymphoepithelioma, an epithelial tumor, consists of poorly differentiated cells with large nucleoli and poorly defined cytoplasmic borders. These tumors frequently contain numerous lymphocytes, and it is important not to mistake the diagnosis with a lymphoma. Some authors have reported that lymphoepitheliomas have a more favorable prognosis than squamous cell carcinoma.  The other 10 to 15 percent of nasopharyngeal tumors are mostly lymphomas but may also include plasmacytomas, juvenile angiofibromas, tumors of the minor salivary gland or chordomas, melanomas and, in children, rhabdomyosarcomas. Approximately 60 to 90 percent of patients with nasopharyngeal cancer present with palpable adenopathy and up to 50 percent of patients with involved nodes have bilateral disease.For staging of nasopharyngeal cancers, the AJCC classification system is used.

The anatomic borders of the nasopharynx generally preclude curative surgical resection with adequate margins. Radiation therapy has therefore been considered the treatment of choice for carcinoma of the nasopharynx. However, most patients present with advanced disease and the treatment strategy should always include a combined treatment of chemotherapy and radiation. Occasionally, a radical or modified radical neck dissection is performed for large nodal metastases as ancillary treatment. actuarial local failure-free survival was 67 percent. A significant trend was found between radiation dose and response.

The 5- and 10-year survivals in patients treated with radiation range from 36 to 62 percent. The outcome depends on a number of factors, including T and N stage, histology, and adequate treatment doses and technique.. Generally, early-stage primary lesions have a superior outcome compared with locally advanced disease.  Some authors report poorer outcome with advanced nodal disease. Hoppe noted a 74 percent 5-year survival in patients with limited nodal (N0, N1) involvement compared with 41 percent in patients with more advanced disease. Perez   on the other hand, were not able to show a difference in survival based on nodal status. Patients with nasopharyngeal carcinoma may also develop distant metastasis and the likelihood appears to be related to the nodal stage at presentation. Vikram  reported that 25 percent of patients with nodal masses of 3 to 5 cm and 50 percent of patients with nodes greater than 6 cm developed distant metastasis. Similarly, Mesic noted a 31 percent incidence of distant metastasis in patients with N2 and N3 disease compared with 7.5 percent with less advanced disease.

Most authors recommend elective nodal irradiation in clinically node-negative patients.Ho  reported, however, a randomized trial of early stage N0 patients comparing observation with prophylactic nodal irradiation. There was no difference in rates of survival or overall failure, although the incidence of nodal failure was slightly higher in the observation arm (19 percent vs. 12 percent). Other investigators have reported nodal relapse rates of 38 to 50 percent in patients not receiving prophylactic nodal irradiation. Lee et al. found a significantly higher rate of distant metastasis in patients with nodal failures (21 percent vs. 6 percent; P < 0.0002). We recommend comprehensive nodal irradiation in all patients. To maximize cure of tumors of the nasopharynx, large radiation fields and high doses are necessary. Several important complications of treatment may occur relating to the proximity of the disease (and radiation therapy field) to the brain. One of the most serious is myelitis. Mesic reported 8 cases of myelitis in 251 patients. Most of these were correlated with a high dose to the spinal cord at the junction of lateral wedge portals and upper neck fields. The use of modern treatment planning should reduce the incidence of this complication to almost zero. Severe fibrosis and/or necrosis of the pharyngeal wall, subcutaneous tissues, or skull base and cranial nerve dysfunction occur in approximately 3 percent of cases. Fibrosis may be minimized by keeping the dose less than 5,000 cGy in electively irradiated areas and using reduced fields to boost gross disease. Persistent or severe xerostomia is reported in approximately 25 to 50 percent of all cases but occurs to some degree in almost all patients. A vigorous program of oral hygiene and fluoride applications is important to prevent dental decay and subsequent mandibular necrosis following dental extraction. Endocrinologic abnormalities following radiation for nasopharyngeal carcinoma have been documented in children and adults.

Some patients with recurrent nasopharyngeal carcinoma may be salvaged with additional radiation. Survival  of re-treated patients ranges from 18 to 41 percent. Extensive intracranial extension may be a contraindication to curative attempts at re-treatment. The outlook after re-treatment is most favorable in patients with recurrence localized to the nasopharynx and who relapse more than 2 years after initial treatment. Patients with lymphoepitheliomas may also have a better outcome after re-treatment.The incidence of complications increases after re-treatment. In the M.D. Anderson series, 8 of 53 patients developed severe complications including brain necrosis (two), radiation myelitis (one), cranial neuropathy (two), and bone or soft tissue necrosis (three). Five of the complications were fatal. The authors found that patients receiving a total cumulative dose of external-beam treatment greater than 10,000 cGy had an increased incidence of severe complications (39 percent vs. 4 percent; P = 0.07).

The Role of Chemotherapy in Nasopharynx Cancers

Nasopharynx carcinoma has exquisite sensitivity to both chemotherapy and radiation. The incidence of metastatic disease may be 30 to 50 percent at diagnosis and development of distant metastases is a frequent cause of failure. Induction chemotherapy with cisplatin and 5-FU followed by radiation yielded a response rate of 93 percent (21 percent CRs) and an overall survival of 67 percent at 6 years in a Phase II trial including 47 patients with very advanced squamous nasopharynx cancer.   In a large randomized international trial an increased disease free survival was shown after induction chemotherapy with cisplatin, epirubicin and bleomycin.   However, an excess of toxic deaths was seen in centers that lack experience with combined treatments. A randomized intergroup study showed significantly prolonged overall survival with concomitant chemoradiotherapy with three cycles of cisplatin (100 mg/m² ) and concomitant once-daily radiotherapy for a total of 70 Gy, followed by three additional cycles of adjuvant chemotherapy with cisplatin and 5-FU. The 3-year survival for radiotherapy only was 46 percent, compared to 76 percent for patients treated with chemotherapy and radiation therapy ( P < 0.001). In light of these results, almost all patients with nasopharynx cancer should receive a combined-modality treatment approach integrating chemotherapy and radiation. Sufficient chemotherapy should be administered because of an elevated risk of distant failure.