This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood nasopharyngeal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Incidence

Nasopharyngeal carcinoma arises in the lining of the nasal cavity and pharynx, and it accounts for about one-third of all cancers of the upper airways in children.[1,2] Nasopharyngeal carcinoma is very uncommon in children younger than 10 years but increases in incidence to 0.8 cases per 1 million per year in children aged 10 to 14 years and 1.3 cases per million per year in children aged 15 to 19 years.[3-5]

The incidence of nasopharyngeal carcinoma is characterized by racial and geographic variations, with an endemic distribution among well-defined ethnic groups, such as inhabitants of some areas in North Africa and the Mediterranean basin, and, particularly, Southeast Asia. In the United States, the incidence of nasopharyngeal carcinoma is higher in black children and adolescents younger than 20 years.[4]

Risk Factors

Nasopharyngeal carcinoma is strongly associated with Epstein-Barr virus (EBV) infection. In addition to the serological evidence of infection in more than 98% of patients, EBV DNA is present as a monoclonal episome in the nasopharyngeal carcinoma cells, and tumor cells can have EBV antigens on their cell surface.[1] The circulating levels of EBV DNA and serologic documentation of EBV infection may aid in the diagnosis.[2] Specific HLA subtypes, such as the HLA A2Bsin2 haplotype, are associated with a higher risk of nasopharyngeal carcinoma.[3]

Histology

Three histologic subtypes of nasopharyngeal carcinoma are recognized by the World Health Organization (WHO):

• Type I is keratinizing squamous cell carcinoma.
• Type II is nonkeratinizing squamous cell carcinoma. Type II is distinguished into type IIa and IIb depending on the presence of lymphoid infiltration.
• Type III is undifferentiated carcinoma. Type III is distinguished into type IIIa and IIIb depending on the presence of lymphoid infiltration.

Children with nasopharyngeal carcinoma are more likely to have WHO type II or type III disease.[1]

Clinical Presentation

Signs and symptoms of nasopharyngeal carcinoma include the following:[1,2]

• Cervical lymphadenopathy.
• Nosebleeds.
• Nasal congestion and obstruction.
• Headache.
• Otalgia.
• Otitis media.

Given the rich lymphatic drainage of the nasopharynx, bilateral cervical lymphadenopathy is often the first sign of disease. The tumor spreads locally to adjacent areas of the oropharynx and may invade the skull base, resulting in cranial nerve palsy or difficulty with movements of the jaw (trismus).

Distant metastatic sites may include the bones, lungs, and liver.

Diagnostic and Staging Evaluation

Diagnostic tests will determine the extent of the primary tumor and the presence of metastases. Visualization of the nasopharynx by an ear-nose-throat specialist using nasal endoscopy and magnetic resonance imaging of the head and neck can be used to determine the extent of the primary tumor.

A diagnosis can be made from a biopsy of the primary tumor or enlarged lymph nodes of the neck. Nasopharyngeal carcinomas must be distinguished from all other cancers that can present with enlarged lymph nodes and from other types of cancer in the head and neck area. Thus, diseases such as thyroid cancer, rhabdomyosarcoma, non-Hodgkin lymphoma including Burkitt lymphoma, and Hodgkin lymphoma must be considered, as well as benign conditions such as nasal angiofibroma, which usually presents with epistaxis in adolescent males, infectious lymphadenitis, and Rosai-Dorfman disease.

Evaluation of the chest and abdomen by computed tomography (CT) and bone scan is performed to determine whether there is metastatic disease. Fluorine F 18-fludeoxyglucose positron emission tomography (PET)–CT may also be helpful in the evaluation of potential metastatic lesions.[1]

Stage Information for Childhood Nasopharyngeal Carcinoma

Tumor staging is performed using the tumor-node-metastasis (TNM) classification system of the American Joint Committee on Cancer (AJCC, 8th edition).[1,2]

More than 90% of children and adolescents with nasopharyngeal carcinoma present with advanced disease (stage III/IV or T3/T4).[3-5] Metastatic disease (stage IVC) at diagnosis is uncommon. A retrospective analysis of data from the Surveillance, Epidemiology, and End Results program reported that patients younger than 20 years had a higher incidence of advanced-stage disease than did older patients.[6]

Prognosis

The overall survival (OS) 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 exceed 80%.[1-8] After controlling for stage, children with nasopharyngeal carcinoma have significantly better outcomes than do adults.[1,7] However, the intensive use of chemotherapy and radiation therapy results in significant acute and long-term morbidities, including subsequent neoplasms.[1-3,6]

Treatment of Childhood Nasopharyngeal Carcinoma

Treatment of nasopharyngeal carcinoma is multimodal and includes the following:

1. Combined-modality therapy with chemotherapy and radiation: High-dose radiation therapy alone has a role in the management of nasopharyngeal carcinoma; however, studies in both children and adults show that combined-modality therapy with chemotherapy and radiation is the most effective way to treat nasopharyngeal carcinoma.[1]; [2-8][Level of evidence: 2A]

   1. Randomized studies have investigated the role of chemotherapy in the treatment of adult nasopharyngeal carcinoma. The use of concomitant chemoradiation therapy was associated with a significant survival benefit, including improved locoregional disease control and reduction in distant metastases.[7,9] The use of neoadjuvant chemotherapy has also resulted in better local and distant control rates, whereas postradiation chemotherapy does not seem to offer any benefit.[9]
   2. In children, four studies used preradiation chemotherapy with different combinations of methotrexate, cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without recombinant interferon-beta.[3,4,10,11][Level of evidence: 2A]

      • These four studies reported response rates of more than 90% and excellent outcomes.
      • Neoadjuvant chemotherapy with cisplatin and 5-FU (with or without leucovorin), followed by chemoradiation with single-agent cisplatin has yielded 5-year overall survival (OS) rates consistently above 80%.[3,4]
      • A preliminary analysis of the NPC-2003-GPOH study, which included a 6-month maintenance therapy phase with interferon-beta, reported a 30-month OS estimate of 97.1%.[4]
   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.[2-4,12] 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.[2,3,12]; [13][Level of evidence: 3iiiA]
   4. A randomized prospective trial compared cisplatin and 5-FU with cisplatin, 5-FU, and docetaxel for the treatment of nasopharyngeal carcinoma in children and adolescents.[14][Level of evidence: 1iiA] The addition of docetaxel was not associated with improved outcome.
   5. Additional drug combinations that have been used in children with nasopharyngeal carcinoma include bleomycin with epirubicin and cisplatin, and cisplatin with methotrexate and bleomycin.[15]
   6. 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.[16,17]
      • Following adult studies and 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.[18][Level of evidence: 3iiiDiv]
2. Surgery: Surgery has a limited role in the management of nasopharyngeal carcinoma because the disease is usually considered unresectable because of extensive local spread.

The use of Epstein-Barr virus–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.[19]

(Refer to the PDQ summary on Nasopharyngeal Cancer Treatment [Adult] for more information.)

Treatment Options Under Clinical Evaluation for Childhood Nasopharyngeal Carcinoma

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.

The following are examples of national and/or institutional clinical trials that are currently being conducted:

• H-25145 (NCT00953420) (Carboplatin, Docetaxel, and Laboratory-Treated T Cells in Treating Patients With Refractory or Relapsed Epstein-Barr Virus [EBV]-Positive Nasopharyngeal Cancer): The objective of this trial is to determine the overall response rate in patients with relapsed/refractory, advanced-stage, EBV-positive nasopharyngeal carcinoma after treatment with docetaxel and carboplatin followed by immunotherapy with EBV-specific cytotoxic T lymphocytes. Individuals aged 10 years and older are eligible for this trial.
• APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
  Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).

Special Considerations for the Treatment of Children With Cancer

Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.[1] Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered for children and adolescents with cancer. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:

• Primary care physicians.
• Pediatric surgeons.
• Radiation oncologists.
• Pediatric medical oncologists/hematologists.
• Rehabilitation specialists.
• Pediatric nurse specialists.
• Social workers.
• Child-life professionals.
• Psychologists.

(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[2] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[3] Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[4] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 persons and, by definition, all pediatric cancers are considered rare. The designation of a pediatric rare tumor is not uniform among international groups, as follows:

• The Italian Rare Tumors in Pediatric Age (TREP) cooperative project defines a pediatric rare tumor as one with an incidence of less than two cases per 1 million population per year and is not included in other clinical trials.[5]
• The Children's Oncology Group has opted to define rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancer, melanoma and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinoma, nasopharyngeal carcinoma, and most adult-type carcinomas such as breast cancer, colorectal cancer, etc.).[6] These diagnoses account for about 4% of cancers diagnosed in children aged 0 to 14 years, compared with about 20% of cancers diagnosed in adolescents aged 15 to 19 years.[7] Most cancers within subgroup XI are either melanomas or thyroid cancer, with the remaining subgroup XI cancer types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.

These rare cancers are extremely challenging to study because of the low incidence of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer such as the PDQ summary on Nasopharyngeal Cancer Treatment (Adult).

Changes to This Summary (01/08/2018)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This is a new summary.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary