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Head and Neck Cancers



Tumor staging is performed utilizing the tumor-node-metastasis classification system of the American Joint Committee on Cancer (AJCC).[9] The majority (>90%) of children and adolescents with nasopharyngeal carcinoma present with advanced disease (stage III/IV or T3/T4).[6,10,11] Metastatic disease at diagnosis is uncommon (stage IVC). A retrospective analysis of data from the Surveillance Epidemiology and End Results (SEER) program reported that patients younger than 20 years had a higher incidence of advanced-stage disease than did older patients, higher risk of developing a second malignancy, and a superior outcome after controlling for stage.[5]


The overall survival of children and adolescents with nasopharyngeal carcinoma has improved over the last four decades; with state-of-the-art multimodal treatment, 5-year survival rates are in excess of 80%.[5,6,11,12] However, the intensive use of chemotherapy and radiation therapy results in significant acute and long-term morbidities.[6,11]


Treatment of nasopharyngeal carcinoma is multimodal:

  1. Combined-modality therapy with chemotherapy and radiation: 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.[6,11,12,13,14,15,16]
    1. Many randomized studies have investigated the role of chemotherapy in the treatment of adult nasopharyngeal carcinoma. In a meta-analysis of ten randomized studies and 2,450 patients, the use of concomitant chemoradiation therapy was associated with a significant survival benefit, including improved locoregional disease control and reduction in distant metastases.[15] Neoadjuvant chemotherapy resulted in a significant reduction in locoregional recurrence only, while postradiation chemotherapy did not offer any benefit.
    2. In children, four studies utilizing preradiation chemotherapy with different combinations of methotrexate, cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without recombinant interferon-beta have reported response rates of more than 90%.[11,12,17,18]
      • Neoadjuvant chemotherapy with cisplatin and 5-FU (with or without leucovorin), followed by chemoradiation with single-agent cisplatin yield 5-year overall survival rates consistently above 80%.[11,12]
      • A preliminary analysis of the NPC-2003-GPOH study, which included a 6-month maintenance therapy phase with interferon-beta, reported a 30-month overall survival estimate of 97.1%.[12]
    3. While nasopharyngeal carcinoma is a very chemosensitive neoplasm, high radiation doses to the nasopharynx and neck (approximately 60 Gy) are required for optimal locoregional control.[6,11,12] The combination of cisplatin-based chemotherapy and high doses of radiation therapy to the nasopharynx and neck are associated with a high probability of hearing loss, hypothyroidism and panhypopituitarism, trismus, xerostomia, dental problems, and chronic sinusitis or otitis.[6,11]
    4. Additional drug combinations that have been used in children with nasopharyngeal carcinoma include bleomycin with epirubicin and cisplatin and cisplatin with methotrexate and bleomycin.[3]
    5. Other approaches to the management of nasopharyngeal carcinoma in children have been evaluated and include the following:
      • Incorporation of high-dose-rate brachytherapy into the chemoradiation therapy approach.[19,20]
      • Following adult data, taxanes have been incorporated into the treatment of childhood nasopharyngeal carcinoma; studies have shown good objective response rates and favorable outcomes with the use of docetaxel in combination with cisplatin.[21][Level of evidence: 3iiiDiv]
  2. Surgery: Surgery has a limited role in the management of nasopharyngeal carcinoma because the disease is usually considered unresectable due to extensive local spread.
  3. EBV-specific cytotoxic T-lymphocytes: The use of EBV-specific cytotoxic T-lymphocytes has shown to be a very promising approach with minimal toxicity and evidence of significant antitumor activity in patients with relapsed or refractory nasopharyngeal carcinoma.[22]

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