Diagnostic tests should determine the extent of the primary tumor and whether there are metastases. Visualization of the nasopharynx by an ear-nose-throat specialist using a mirror, examination by a neurologist, and magnetic resonance imaging of the head and neck can be used to determine the extent of the primary tumor. Evaluation of the chest and abdomen by computed tomography and bone scan should also be performed to determine whether there is metastatic disease. The levels of EBV and antibody to EBV should also be measured.[2,8]
Tumor staging is performed utilizing the tumor-node-metastasis classification system of the American Joint Committee on Cancer (AJCC). The majority (>90%) of children and adolescents with NPC present with advanced disease (stage III/IV or T3/T4). Metastatic disease at diagnosis is uncommon (stage IVC). Outcome is directly related to the stage of the disease, with overall survival ranging from 80% for stage I and stage II to 40% for stage III. Other factors associated with an inferior outcome include node size larger than 6 cm, radiation dose less than 60 Gy, and poor response to chemotherapy. A retrospective analysis of data from the Surveillance Epidemiology and End Results (SEER) program reported that patients younger than 20 years had a higher risk of developing a second malignancy, a higher incidence of advanced stage disease when compared with older patients, and a superior outcome after controlling for stage. The overall survival of children and adolescents with NPC has improved over the last four decades and about 80% are cured.[5,6] Although the outcome has improved with the use of chemotherapy and radiation therapy, significant morbidities do occur.
Surgery has a limited role in the management of nasopharyngeal carcinoma because the disease is usually considered unresectable due to extensive local spread.
High-dose radiation therapy alone has had a role in the management of low-stage nasopharyngeal carcinoma, but studies in both children and adults show that combined modality therapy with chemotherapy and radiation is the most effective way to treat nasopharyngeal carcinoma.[6,11,12,13,14,15] In a meta-analysis of studies adding chemotherapy to radiation therapy in adults with nasopharyngeal carcinoma, concomitant chemotherapy plus radiation therapy offered a significant benefit for survival, locoregional disease control, and reduction in distant metastases. Neoadjuvant chemotherapy resulted in a significant reduction in locoregional recurrence only, while postradiation chemotherapy did not offer any benefit. In children, two studies utilizing preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without recombinant interferon-beta reported response rates of more than 90%.[16,17] Initial chemotherapy with cisplatin and docetaxel prior to radiation in young patients with nasopharyngeal carcinoma is associated with objective responses and favorable outcomes after radiation therapy.[Level of evidence: 3iiiDiv] Radiation therapy doses utilized in both studies were approximately 60 Gy. Investigators at St. Jude Children's Research Hospital performed a retrospective review of 59 young patients with NPC. They reported better outcome for patients whose treatment included cisplatin and for patients who received more than 50 Gy of radiation to the primary tumor and to the regional lymph nodes. These treatments were associated with a high probability of hearing loss, hypothyroidism, trismus, xerostomia, dental problems, and chronic sinusitis or otitis. Additional drug combinations that have been used in children with nasopharyngeal carcinoma include bleomycin with epirubicin and cisplatin, cisplatin and fluorouracil, and cisplatin with methotrexate and bleomycin. Incorporation of high-dose-rate brachytherapy into the chemoradiation therapy approach has been reported, but its role in the management of nasopharyngeal carcinoma in children is unknown.[19,20]