Seminars in Radiation Oncology
Volume 20, Issue 1 , Pages 52-57, January 2010

Head and Neck Carcinomas Across the Age Spectrum: Epidemiology, Therapy, and Late Effects

  • Karen J. Marcus, MD

      Affiliations

    • Division of Radiation Oncology, Children's Hospital Boston, Boston, MA
    • Corresponding Author InformationAddress reprint requests to Karen J. Marcus, MD, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115
    • ,
  • Roy B. Tishler, MD, PhD

      Affiliations

    • Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Article Outline

Carcinomas of the head and neck occur in both children and adults, but notable differences exist in their relative frequency, pathologic subtypes, etiologies, presenting symptoms, and late effects. In contrast, treatment strategies are similar depending on the disease type and distribution at the time of diagnosis. Thus, in adult patients, squamous cell carcinomas or one of its variants are the most common malignancies in the head and neck. However, in children, cancers of the head/neck are most commonly rhabdomyosarcomas, lymphomas, including Hodgkin's lymphoma, lymphoblastic lymphomas, and Burkitt's lymphoma or neuroblastoma. Epithelial cancers are unusual in the pediatric population, with the exception of nasopharyngeal carcinoma. Although nasopharyngeal carcinoma is a rare disease in children, representing less than 1% of childhood cancers, it does constitute 20%-50% of pediatric malignancies of the nasopharynx. This is one of the few malignant tumors in children that arise from the epithelium. Despite the differences between the diseases in children from that in adults, the management strategy has been based largely on the experience in adults. This review will describe the epidemiology, etiology, management, and late effects in children and adults, and offer explanations for both the similarities and differences.

 

Epithelial cancers of the head and neck are common in adults, but are rare in children. Nasopharyngeal carcinoma (NPC) is the frequent epithelial head and neck cancer in children, and thus offers the opportunity for comparison of the distribution of pathologic subtypes, pathogenesis, clinical presentation, treatment, and therapeutic sequelae across the age spectrum. Explanations for these differences are sometimes identifiable, whereas at other times are speculative. Cancers of the head/neck in children are most commonly rhabdomyosarcomas, lymphomas, or neuroblastoma, with cancer of the NPC constituting 20%-50% of pediatric malignancies of the nasopharynx.1 In adults, squamous cell carcinomas (SCC) or one of its variants are the most common malignancies in the head and neck. These types of tumors are highly unusual in the pediatric population, with the exception of NPC. Carcinoma of the nasopharynx is a rare disease in children, representing less than 1% of childhood cancers.1, 2 When nasopharynx cancer does occur in children, it is in association with Epstein-Barr viral (EBV) infection; the histologic subtype is undifferentiated, and there is a high incidence of locally advanced disease at presentation, which is true for many, but not for all, of the adult cases. Despite some differences between the disease in children and adults, the management strategy has been based largely on the experience in adults. This review will describe the epidemiology, etiology, management, and late effects in both children and adults.

Back to Article Outline

Epidemiology/Pathology 

The World Health Organization (WHO) classifies NPC into 3 subtypes (Table 1). The neoplastic component is epithelial although lymphoid, plasmoid, and eosinophilic cell infiltration is common in types II and III. Type I NPC is also known as squamous cell keratinizing and type II is squamous cell non-keratinizing. Type III, also called lymphoepithelioma or Schminke tumor, is characterized by undifferentiated round cells with prominent nucleoli and by an infiltration of nonmalignant lymphoid cells. Type IIIa demonstrates cells with large nucleoli and eosinophilic cytoplasm; type III b cells have small nucleoli and basophilic cytoplasm.3 NPC in children is almost always the undifferentiated variant, which is typically an endemic tumor with a geographic distribution, including southern parts of China, South-East Asia, the Mediterranean basin, and Alaska. The incidence and histology of NPC varies greatly on the basis of ethnic and geographic factors. For example, the rate per 100,000 patients is ∼17 for males in Singapore and <1 for United States Caucasians. There is a bimodal age distribution in some populations in North America and the Mediterranean, with an early peak incidence at 10-20 years and a second at 40-60 years. The bimodal distribution is typically not seen in endemic populations.4 Median age for the development of NPC in children is 13 years, with a male-to-female ratio of 1.8:1.5 The proportion of all patients with NPC who are age <16-year does vary by geographic region. In China, children account for 1%-2% of all cases of NPC, 10% in the USA, 12% in Israel, 2% in Turkey, and 18% in Uganda.5, 6, 7 These differences reflect the multifactorial etiology of the disease and the varying influences of environmental as well as genetic factors.

Table 1. World Health Organization Classification of Nasopharyngeal Carcinoma (NPC)
Type ISquamous cell carcinoma; moderate-well diffentiated keratin-producing cells; intercellular bridges
Type IINonkeratinizing carcinoma; mature to anaplastic cells; minimal keratin
Type IIIUndifferentiated cells, including lymphoepithelioma, anaplastic, clear cell, and spindle cell variants

Back to Article Outline

Etiology 

EBV has been implicated as a causative agent in NPC on the basis of the serologic findings of high antibody titres of immunoglobulin G (IgG) and immunoglobulin A (IgA) directed against the viral capsid antigen found in patients with NPC, particularly the undifferentiated variant. In some endemic regions, such as southern China, the measurement of IgA antibodies specific to EBV is used in screening for NPC in high-risk groups. Antibody titer measured during and after treatment indicates disease response. The presence of the EBV genome in tumor cells confirms the link between the disease and the virus. EBV infection in the nasopharynx is an early event, as demonstrated by the presence of clonal EBV genomes in preinvasive dysplastic lesions. Children with NPC typically have altered immunity at diagnosis and after treatment.8 T-cell immunity is critical in the suppression of EBV-infected B-cell proliferation. Tumor-infiltrating lymphocyte responses are impaired in patients with NPC.3 Findings of altered immunity are not characteristic of NPC in adults.

The EBV genome is double-stranded DNA encoding over 100 genes. Cells that are latently infected with EBV express 10 genes from the genome. These genes include 6 nuclear proteins Epstein-Barr nuclear antigen (EBNAs), latent membrane proteins (LMPs), and 2 nontranslated RNA molecules (EBER). These genes are implicated in EBV-mediated cell-growth. The EBV gene-expression found in the undifferentiated variant of NPC includes EBNA1, LMP1, LMP2, and EBERs. EBNA1 plays a role in viral replication and maintenance of the viral genome during cell division. LMP1 has oncogenic properties, upregulating cellular proteins that inhibit apoptosis. LMP2 and EBERs are also important for oncogenesis and prevention of apoptosis.9, 10 The development of NPC is thought to involve multiple steps beginning with EBV infection. EBV infection results in increased expression of LMP1 and p53 in epithelial cells. Bcl-2 expression is expressed in 80% of adult cases of NPC but is not associated with childhood NPC.11

In addition to the role of EBV in the etiology of the undifferentiated variant of NPC, there is evidence of a genetic determinant of NPC. Individuals with HLA A2 Bsin2 haplotype, Aw19, Bw46, and B17 types have an increased risk of NPC.12 According to cytogenetic studies, it seems that deletions in tumor suppressor genes may be involved in the promotion of malignancy. Several molecular changes occur in the development of NPC, including inactivation of p53 and rearrangements of the retinoblastoma tumor suppressor genes.13

There are different implications for the mechanisms of development for the different pathologic types of NPC, as summarized.4 Type I is associated with patients in low-risk populations who developed the disease; it is associated with exposure (tobacco, environmental) as a causative agent and characterized by a later onset in adulthood. Generally, the mechanism for younger patients with type II/III tumors is associated with EBV infections and underlying predisposition. Type III tumors are the common histologic type for endemic populations. The pathway identified in this setting is chronic dietary exposure in combination with EBV infection.4 In addition, the subsequent clinical behavior depends on the histologic subtype. Typically, the undifferentiated type of tumors present with more regional and distant disease compared with the keratinizing SCCs. However, the undifferentiated tumors are more responsive to radiation, and patients with SCC generally do worse clinically with lower overall survival and disease-free survival.

Back to Article Outline

Clinical Presentation 

The nasopharynx is a cuboidal structure, continuous with and posterior to the nasal cavity, bounded laterally by the cartilaginous portion of the eustachian tubes, inferiorly by the roof of the soft palate, posteriorly by the pharyngeal wall, and superiorly by the floor of the sphenoid sinus and clivus. The anatomy of the nasopharynx also means that local tumor growth and extension can cause nasal obstruction, epistaxis, conductive hearing loss, earache, or tinnitus. Invasion of the base of skull can lead to cranial nerve involvement. Symptoms of cranial nerve involvement include ptosis, diplopia, swallowing difficulties, trismus, shoulder weakness, and taste disturbance. The lymphatic drainage of the nasopharynx is through multiple pathways, including adenoidal tissue at the junction of the roof and posterior wall of the postnasal area, the internal jugular chain, the retropharyngeal nodes, and the spinal accessory chain. The multiple lymphatic pathways explain the high incidence of lymphatic metastases in NPC.

The most common presenting symptom of NPC in children is a painless mass in the neck due to regional lymph node involvement. The range in the duration of these symptoms in children is broad: 1-24 months, median 5 months, in 1 series of 50 children.5

In adults, about one third of patients will have a painless neck mass as their presenting symptom. In addition, the vast majority of adult patients will have lymphadenopathy at initial presentation, even if this is not the symptom that brings the patient to medical attention. Roughly one third of adults will present with unilateral ear symptoms of congestion or hearing loss. In an adult, unilateral ear symptoms are a serious problem or a sign of a serious problem, until proven otherwise. This is in marked contrast with the situation in children, where unilateral ear findings are common and certainly not indicative of a serious problem, but much more likely to be infectious. About 20% of adults will present with cranial neuropathies, and of these it is most common to observe CN–V and CN–VI compromise at presentation. Multiple well-characterized distinct patterns of cranial neuropathies are observed, depending on the route of the primary disease extension and which of the skull base foramina are involved.14

Back to Article Outline

Evaluation and Staging 

The initial physical examination of the child with NPC will often detect cervical lymphadenopathy. A nasopharyngeal mass may be evident on initial inspection. Radiographic imaging with magnetic resonance imaging of the primary and nodal areas and computerized tomography (CT) to evaluate the base of skull for bony erosion are performed. An endoscopic examination under anesthesia and biopsy of the primary tumor is done. Positron emission tomography is widely used. Bone, chest, and abdominal CT scans are performed to evaluate the child for distant metastatic disease to the lung, bone, and liver. A bone marrow biopsy is indicated for children with advanced disease, and an examination of the cerebrospinal fluid is performed if there is base of skull erosion or intracranial extension. In addition, viral capsid antigen IgA levels may be helpful to monitor response and recurrence. Pediatric NPC is an uncommon diagnosis, and as such it is not considered early on in the evaluation of patients with cervical lymphadenopathy. Thus, pediatric patients frequently have locally advanced disease at the time of diagnosis.15

The staging system most commonly used for the staging of NPC is the American Joint Committee for Center Staging (Table 2).16 Most children present with locally advanced stage III or IV disease.17, 18 Despite the high percentage of children with local-regional disease, distant metastases at diagnosis occur infrequently.

Table 2. American Joint Committee on Cancer Nasopharyngeal Cancer Staging Classification
T stageExtent of primary tumor
T1Confined to nasopharynx
T2Extends to soft tissues
2aTumor extends to oropharynx or nasal cavity without parapharyngeal extension
2bAny tumor with parapharyngeal extension
T3Invades bony structures and/or paranasal sinuses
T4Intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hypopharynx, and orbit or masticator space
N stageLymph node disease
N0No lymph node metastases
N1Unilateral lymph node(s) ≤ 6 cm
N2Bilateral lymph nodes ≤ 6 cm
N3Lymph node metastases
3aGreater than 6 cm
3bExtension to supraclavicular fossa
M stageDistant metastases
M0Absent
M1Present
Stage GroupT StageN StageM Stage
IT1N0M0
IIAT2aN0M0
IIBT2bN0M0
T1-T2bN1M0
IIIT3N0-1M0
T1-3N2M0
IVAT4N0-2M0
IVBT1-4N3M0
IVCT1-4N0-3M1

Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, pp 44-45, 7th ed. (2009), published by Springer Science and Business Media LLC, www.springerlink.com.

Similar staging/evaluation considerations are used for adult patients. CT and magnetic resonance imaging are complementary and both necessary in evaluating the local disease extent. In addition to the local disease sites of involvement described above, nodal involvement with a focus on upper cervical, posterior neck, and retropharyngeal regions need to be assessed. This is helpful for staging and essential for accurate dosing in the radiation planning process. In contrast with the other SCC in head and neck sites, NPC does not share the same nodal staging system. A positron emission tomography/CT is frequently used as a screening study for unsuspected nodal involvement or distant metastases. About 20% of patients will be found to have distant metastases at the time of presentation, in contrast to the pediatric population, where distant metastases are uncommon. For patients with particularly advanced disease, additional metastatic workup, including chest/abdominal CT, can be considered.

Back to Article Outline

Treatment 

Before the initiation of treatment, dental evaluation, treatment, and prophylaxis are recommended. Baseline endocrine studies should be obtained and audiograms performed. Hearing evaluation is important for both adults and children, particularly the latter. Radiation therapy can diminish hearing by its effects on the inner ear and Eustachian tube dysfunction that can result in a temporary build-up of fluid. In addition, the most commonly used drug in the treatment of NPC is cisplatin, which is ototoxic.

Back to Article Outline

Current Management 

The current management of NPC in children involves chemotherapy and radiotherapy, although the sequence of administration and specific chemotherapy regimen used vary. Undifferentiated NPC responds well to radiotherapy; however, 5-year survival rates with radiotherapy alone are only 20%-60% in pediatric series. Advances in imaging as well as technological advances in radiotherapy have come at the same time as combined modality treatment approaches that have joined to improve the survival rates to 75%-91%.3, 17, 19

For definitive treatment of NPC, radiation based therapy is the mainstay of treatment for NPC. The disease generally responds well to treatment, and in particular type III is radiosensitive. On the basis of local anatomic constraints, surgery has no role in upfront definitive therapy. However, radical neck dissection may be indicated if there seems to be persistent tumor in the lymph nodes in the neck after chemotherapy and radiotherapy, or if there is isolated recurrence in the neck after treatment. Early stage tumors (T1/2, N0) are treated with radiation alone. More advanced tumors integrate systemic therapy into definitive management. This is delivered as concurrent treatment, as well as using neoadjuvant and adjuvant chemotherapy schedules.

The delivery of radiation therapy for nasopharynx cancer is complicated and technically difficult due to the pathways of spread and proximity of multiple sensitive normal tissues. Dosing for the primary tumor using conventional techniques is 66-70 Gy to the primary and gross nodal disease. High risk nodes receive ≥60 Gy and uninvolved low-risk areas 50-54 Gy. Historically, this has been delivered using a series of shrinking fields, with treatment to the entire field at 180-200 cGy/d. Doses >66 Gy to the primary site have been demonstrated to deliver improved results. The treatment volume includes: the nasopharynx, the posterior 2 cm of the nasal cavity, posterior ethmoid sinuses, entire sphenoid sinus, base of skull, the foramen ovale, the carotid canal, the foramen spinosum, pterygoid fossae, the posterior one third of the maxillary sinus, the oropharyngeal wall to the midtonsillar fossa, and the retropharyngeal nodes. The cervical nodes on both sides of the neck are treated as well as the supraclavicular nodes. If the tumor invades the base of the skull or if the patient manifests involvement of cranial nerves II-VI, the tumor volume is increased to cover the base of the brain and adjacent portions of the middle and anterior cranial fossa. The treatment volume is modified and expanded based on the imaging of the tumor.

Nasopharynx is one of the sites in the head and neck where the benefit of more conformal therapies, such as intensity modulated radiation therapy (IMRT), has proven to be significant in improving local control and decreasing acute and late toxicities.20 Achieving dose differentials between, for example, a tumor invading the skull base and the brainstem is challenging if conventional techniques are used. There have been multiple studies of IMRT in this disease, demonstrating both theoretic and practical benefits to inverse planning techniques over standard. Planning studies demonstrate improvements in dose distributions, local control rates, and normal tissue effects. IMRT is clearly the radiation standard of care for nasopharynx cancer in adult patients. Although there are fewer data in children in dose distributions, there are similar issues in the pediatric population. However, there is certainly more of a concern for the sequelae of treatment in this setting, as the increased monitor units and dose to normal tissue is a more concerning issue in young patients. Highly conformal technologies, including proton beam and IMRT are being used now and may improve the acute and late toxicity profiles along with local control. The benefit of conformal treatment delivery has been shown in a comparison of conventional and IMRT techniques in pediatric nasopharyngeal cancers.21 In children, decreased exposure of normal tissue to radiotherapy is an important goal. Newer imaging combined with these conformal techniques can also ensure that the tumor receives full dose while minimizing doses to the normal tissues.

For advanced tumors, both local-regional control and distant metastatic disease are improved with the addition of systemic therapy, though there is no consensus on the optimal timing, drugs, and the magnitude of this benefit. The Intergroup study22 clearly established a combination of chemotherapy and radiation as the better treatment compared with radiation alone for advanced disease. A somewhat unorthodox chemotherapy combination was used with concurrent cisplatin and radiation followed by adjuvant cisplatin-5-FU. In the management of adult head and neck malignancies, this is the only disease with evidence for a role of adjuvant systemic therapy following radiation-based treatment. In contrast with the use of systemic therapy in adults, the use of adjuvant chemotherapy is a more common approach in pediatric malignancies, for example, in treating rhabdomyosarcoma, Ewing's sarcoma, and Wilms' tumor. In most situations, this is considered the standard of care for patients with advanced disease in the absence of enrolling patients on a clinical trial. Multiple questions have been raised about the population in this study, as it is not in an endemic group. In addition, the results in the radiation alone arm, which were not considered optimal, have come under scrutiny. However, the underlying findings are firmly established. Subsequent studies have continued to investigate the role of systemic therapy for advanced disease. The use of induction chemotherapy is actively being examined in other head and neck cancers in adults, and is being investigated for nasopharynx cancer.23 Concurrent chemotherapy has been generally accepted to have a role in management of locally advanced disease, as it has for other adult head and neck sites. A large phase III study in Hong Kong has yielded some of the strongest support for this approach.24, 25 The overall question of the role of chemotherapy has also been addressed in a meta-analysis, confirming the above results.26 Combinations of concurrent and induction systemic therapy, termed sequential therapy, are also showing promising results.27

The vast majority of childhood NPC is EBV-related. This may represent a different entity from the disease type observed more frequently in adults. However, due to the rarity of this disease in the pediatric age group, the management of NPC in children has been largely adapted from the treatment of the disease in adults. Although most children present with locally advanced disease, the goal of treatment is cure. Treatment with radiotherapy alone, using high dose to the primary and involved nodes with moderate dose to the uninvolved nodes, has resulted in 5-year survivals of 40%-60% in pediatric series.5, 28 High-dose radiotherapy in children has resulted in significant long-term morbidity, including xerostomia, growth disturbance, hormonal dysfunction, trismus, and secondary malignancies. In addition to long-term morbidity from radiotherapy alone, systemic failures in patients with locally advanced disease stressed the need for improved systemic treatments. The addition of concurrent and adjuvant chemotherapy has improved survival for adults with advanced NPC compared with radiotherapy alone.22

The optimal radiotherapy dose in childhood NPC has not been definitively established. Although doses >60-Gy do seem to result in superior local control, others suggest a lack of correlation between dose, local relapse, and survival.17, 29, 30 Despite the lack of definite evidence, recommendations are to administer 50-72 Gy to the primary tumor in children age >10 years, and a 5%-10% reduction in these doses for younger children.

Locoregional control in children treated with radiotherapy alone ranges from 34%-74%, but many patients recur with either systemic disease or local recurrence resulting in disappointing overall survivals of 30%-66%.17, 28 To improve the outcome in children with NPC, chemotherapy has been introduced based on this approach in adults with this cancer. Several chemotherapy agents have shown activity in NPC, including adriamycin, epirubicin, cisplatin, etoposide, bleomycin, fluorouracil, methotrexate, and vinca alkaloids. The addition of adjuvant chemotherapy improved the survival in adults with advanced NPC.22 Randomized trials in the pediatric population to study the effect of chemotherapy in NPC are difficult to carry out due to the limited number of patients. Combined modality treatment regimens in childhood NPC incorporate cisplatin together with other agents, such as fluoruracil, methotrexate, bleomycin, vinblastine, or docetaxel.17, 29 The local control in the published series of combination chemotherapy with radiotherapy before or after chemotherapy is 70%-100% and the overall survival 50%-90%. Pediatric treatment regimens have used induction chemotherapy, followed by radiotherapy and then postradiotherapy chemotherapy for additional cycles. Although some retrospective studies have failed to show survival benefit to the use of chemotherapy over radiotherapy alone, other reports have shown improvements in disease-free and overall survivals compared with historical controls. Despite the lack of randomized evidence, the use of cisplatin-based chemotherapy has gained acceptance in the treatment of NPC in children. The use of concomitant chemoradiotherapy in the treatment of NPC treats systemic disease early, attacks local disease, and has the added potential benefit of radiosensitization to augment local control. For children, the role of concomitant therapy in the management of NPC has not been proven.

Back to Article Outline

Late Effects of Treatment 

A range of toxicities is associated with delivering radiation to the head and neck/base of skull regions, as is required for effective treatment of NPC. For both acute and long-term toxicities, the spectrum and intensity of these effects are changing, as the newer delivery techniques will change the consequences of a course of radiation. In acute effects, these are primarily mucositis, xerostomia, and skin irritation and can lead to discomfort requiring narcotic analgesia and polyethylene glycol support. Longer-term consequences are predominantly neurologic in nature, given the proximity of the nasopharynx to the CNS. These include temporal lobe necrosis, optic pathway damage, and less frequently cranial neuropathies. Ear complications include serous otitis and direct effects from bolus cisplatin or deficits from radiation dose to the inner ear. Patients are also at risk from endocrinologic complications, as well as bone/soft tissue necrosis, such as trismus, fibrosis, and osteoradionecrosis. Second malignancies are always a consideration in patients cured of a primarily tumor, but in the adult population, this is observed much less for NPC patients compared with other head and neck sites. However, the development of secondary malignancy is expected to be more of a problem in pediatric patients given their longer time frames for risk after treatment, though it may not have been identified yet due to small numbers in reported series. The long-term morbidities in children include hypothyroidism in at least 73% and pituitary dysfunction resulting in growth hormone and other hormonal deficiencies in 30% of survivors. Musculoskeletal abnormalities, such as fibrosis and muscle hypoplasia, xerostomia, dental caries, decreased hearing (particularly in children treated with plating-based chemotherapy), and secondary malignancies account for 6%-8%.3, 17, 19, 31 There are few reports on the late toxicities of treatment in children, which can be severe. However, the treatment is aggressive if it is to be successful. Newer radiotherapy techniques and more effective chemotherapy may help to ameliorate these toxicities.

Back to Article Outline

Conclusions 

Epithelial cancers of the head-neck are common in adults, but are rare in children. However, cancer of the nasopharynx, the most common epithelial malignancy of the head-neck in children, provides an opportunity for a comparison of a head-neck malignancy observed both in children and adults (Table 3). The etiology of nasopharynx cancer does vary with age and geography. EBV is the chief underlying cause in children, whereas in adults there are other etiologic factors and environmental associations in addition to EBV. The presentation in both age groups tends to be of locally advanced disease. Despite the broad age range of the patients with nasopharynx cancer, the management across age groups is similar, based on high-dose radiotherapy often accompanied by concurrent chemotherapy. The outcomes in children overall are superior to those in adults, but the late effects in children are severe, including hormonal deficiencies, musculoskeletal abnormalities, xerostomia, osteoradionecrosis, trismus, and secondary malignancies. In adults, the late effects do include most of these aforementioned toxicities, with the exception of musculoskeletal growth abnormalities. Continuing research into the causes of nasopharynx cancer and therapeutic trials are needed to improve the outcome and diminish the late toxicities for all ages.

Table 3. Comparison of Childhood and Adult NPC
Childhood NPCAdult NPC
WHO classificationType III undifferentiatedType I, II, or III
Stage at presentation80% AJCC stage 4 (T4 or N2-3)15% Stage I, 32% II, 28% III, 25% IVa
M:F1.8:12-3:1
EBV related pathogenesisYesYes, also non-EBV mechanisms
Bcl-2 relatedNoYes
ManagementChemoradiotherapyRT alone early stage; chemoradiotherapy for advanced disease
5-yr overall survival50%-90%
Stage I/II—80%-95%

Stage III/IV—60%-80%b

aEndemic population by American Joint Committee for Center Staging ed 6th.

bEndemic population by American Joint Committee for Center Staging ed 5th.

Back to Article Outline

References 

  1. Deutsch M, Mercado R, Parsons JA. Cancer of the nasopharynx in children. Cancer. 1978;41:1128–1133
  2. Ingersoll L, Woo SY, Donaldson S. Nasopharyngeal carcinoma in the young: A combined M.D. Anderson and Stanford experience. Int J Radiat Oncol Biol Phys. 1990;19:881–887
  3. Mertens R, Granzen B, Lassay L. Nasopharyngeal carcinoma in childhood and adolescence: Concept and preliminary results of the cooperative GPOH study NPC-91 (Gesellschaft fur Padiatrische Onkologie und Hamatologie). Cancer. 1997;80:951–959
  4. Bray F, Haugen M, Moger TA. Age-incidence curves of nasopharyngeal carcinoma worldwide: Bimodality in low-risk populations and aetiologic implications. Cancer Epidemiol Biomarkers Prev. 2008;17:2356–2365
  5. Ayan I, Altun M. Nasopharyngeal carcinoma in children: Retrospective review of 50 patients. Int J Radiat Oncol Biol Phys. 1996;35:485–492
  6. Levine PH, Connelly RR, Easton JM. Demographic patterns for nasopharyngeal carcinoma in the United States. Int J Cancer. 1980;26:741–748
  7. Har-Kedar I, Chaitchik S, Hercberg A. Nasopharyngeal carcinoma at the Tel-Hashomer Government Hospital, Israel (A 20 year survey (1951-1970)). Clin Radiol. 1974;25:403–407
  8. Hu DE, Ling XS, Hu J. The effects of radiotherapy on the immune system of patients with nasopharyngeal carcinoma. Br J Radiol. 1988;61:305–308
  9. Vasef MA, Ferlito A, Weiss LM. Nasopharyngeal carcinoma, with emphasis on its relationship to Epstein–Barr virus. Ann Otol Rhinol Laryngol. 1997;106:348–356
  10. Cohen JI. Epstein–Barr virus infection. N Engl J Med. 2000;343:481–492
  11. Preciado MV, Chabay PA, De Matteo EN. Epstein Barr virus associated pediatric nasopharyngeal carcinoma: Its correlation with p53 and bcl-2 expression. Med Pediatr Oncol. 2002;38:345–348
  12. Vokes EE, Liebowitz DN, Weichselbaum RR. Nasopharyngeal carcinoma. Lancet. 1997;350:1087–1091
  13. Claudio PP, Howard CM, Fu Y. Mutations in the retinoblastoma-related gene RB2/p130 in primary nasopharyngeal carcinoma. Cancer Res. 2000;60:8–12
  14. Wang CC. Radiation Therapy for Head and Neck Neoplasms. (ed 3). New York, NY: Wiley-Liss; 1997;
  15. Stambuk HE, Patel SG, Mosier KM. Nasopharyngeal carcinoma: Recognizing the radiographic features in children. Am J Neuroradiol. 2005;26:1575–1579
  16. Fleming I, Cooper J, Henson D. AJCC Cancer Staging Manual. (ed 5). Philadelphia, PA: Lippincott-Raven; 1997;
  17. Wolden SL, Steinherz PG, Kraus DH. Improved long-term survival with combined modality therapy for pediatric nasopharynx cancer. Int J Radiat Oncol Biol Phys. 2000;46:859–864
  18. Ayan I, Kaytan E, Ayan N. Childhood nasopharyngeal carcinoma: From biology to treatment. Lancet Oncol. 2003;4:13–21
  19. Zubizarreta PA, D'Antonio G, Raslawski E. Nasopharyngeal carcinoma in childhood and adolescence: A single-institution experience with combined therapy. Cancer. 2000;89:690–695
  20. Wolden SL, Chen WC, Pfister DG. Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: Update of the Memorial Sloan-Kettering experience. Int J Radiat Oncol Biol Phys. 2006;64:57–62
  21. Laskar S, Bahl G, Muckaden M. Nasopharyngeal carcinoma in children: Comparison of conventional and intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2008;72:728–736
  22. Al-Sarraf M, LeBlanc M, Giri PG. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: Phase III randomized intergroup study 0099. J Clin Oncol. 1998;16:1310–1317
  23. Ma J, Mai HQ, Hong MH. Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol. 2001;19:1350–1357
  24. Chan AT, Teo PM, Ngan RK. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: Progression-free survival analysis of a phase III randomized trial. J Clin Oncol. 2002;20:2038–2044
  25. Chan AT, Leung SF, Ngan RK. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005;97:536–539
  26. Baujat B, Audry H, Bourhis J. Chemotherapy in locally advanced nasopharyngeal carcinoma: An individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys. 2006;64:47–56
  27. Hui EP, Ma BB, Leung SF. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009;27:242–249
  28. Jenkin RD, Anderson JR, Jereb B. Nasopharyngeal carcinoma—a retrospective review of patients less than thirty years of age: A report of Children's Cancer Study Group. Cancer. 1981;47:360–366
  29. Varan A, Ozyar E, Corapcioglu F. Pediatric and young adult nasopharyngeal carcinoma patients treated with preradiation cisplatin and docetaxel chemotherapy. Int J Radiat Oncol Biol Phys. 2009;73:1116–1120
  30. Lombardi F, Gasparini M, Gianni C. Nasopharyngeal carcinoma in childhood. Med Pediatr Oncol. 1982;10:243–250
  31. Uzel O, Yoruk SO, Sahinler I. Nasopharyngeal carcinoma in childhood: Long-term results of 32 patients. Radiother Oncol. 2001;58:137–141

PII: S1053-4296(09)00065-4

doi:10.1016/j.semradonc.2009.09.004

Seminars in Radiation Oncology
Volume 20, Issue 1 , Pages 52-57, January 2010

Article Tools