title: Diagnosis and Treatment of Nasopharyngeal Carcinoma in Children and Adolescents - Recommendations of the GPOH-NPC Study Group.
abstract: Nasopharyngeal carcinoma (NPC) is a rare malignant tumor arising from epithelial cells of the nasopharynx. Its incidence is highest in Southeast Asia. Age distribution of NPC is bimodal, with one peak in young adolescents and another in patients 55-59 years of age. EBV appears to be the primary etiologic agent in the pathogenesis, environmental factors such as nitrosamines and genetic factors are contributory. NPC is most commonly diagnosed in locally advanced stages, with lymph node metastases occurring in up to 90% of patients. About 5-10% of patients present with distant metastases. Diagnosis of NPC is made histologically, supported by an abnormal anti-EBV-VCA IgA titer and elevated plasma EBV-DNA load. Superior results in children and adolescents with advanced locoregional NPC, with overall and event-free survival rates>90%, have been achieved by neoadjuvant chemotherapy with 5-fluoruracil and cisplatin, followed by synchronous radiochemotherapy and subsequent maintenance therapy with interferon-ß as demonstrated by the 2 prospective studies GPOH-NPC-91 and -2003. Response to therapy can be assessed by PET-imaging and in patients with complete remission after neoadjuvant chemotherapy, the radiation dose to the primary tumor can be safely reduced from 59.4 to 54.4 Gy. Since the majority of long term sequalae such as xerostomia, skin and tissue fibrosis are caused by high radiation dosages, radiotherapy modalities such as intensity-modulated radiotherapy should be used to efficiently spare non-tumorous tissue. For patients with metastatic disease and relapse, survival chances are low. New treatment strategies, such as the application of EBV-specific T-lymphocytes should be considered for these patients.
authors.affiliation: Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University , Aachen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Kontny
authors.affiliation: Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University , Aachen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Franzen
authors.affiliation: Children's Hospital München-Schwabing, Technische Universität, München, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Behrends
authors.affiliation: Prof.-Hess-Kinderklinik, Klinikum Bremen-Mitte, Bremen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bührlen
authors.affiliation: Department of Radiotherapy and Radiation Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Christiansen
authors.affiliation: Pathogenesis of Virus Associated Tumors (F100), German Cancer Research Center, Heidelberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Delecluse
authors.affiliation: Medical Faculty, Department of Radiation Oncology, RWTH Aachen University, Aachen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Eble
authors.affiliation: Pediatric Hematology, Oncology and Stem Cell Transplantation, Dr. von Hauner'sches Kinderspital, Ludwig-Maximilians-University, München, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Feuchtinger
authors.affiliation: Department of Radiotherapy, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Gademann
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Granzen
authors.affiliation: Hannover Medical School, Pediatric Hematology/Oncology, Hannover, Germany.
authors.forename: C P
authors.initials: CP
authors.lastname: Kratz
authors.affiliation: Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University , Aachen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Lassay
authors.affiliation: Kindertumorregister der GPOH, Sektion Kinderpathologie, Universitätsklinikum Schlewig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Leuschner
authors.affiliation: Department of Nuclear Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: F M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: Medical School Hannover, Institute of Virology, Hannover, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schmitt
authors.affiliation: Section of Paediatric Radiology, University Medical Center Mainz, Mainz, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Staatz
authors.affiliation: University Essen, Westgerman Protontherapycenter Essen, Essen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Timmermann
authors.affiliation: Pediatric Oncology, Otto von Guericke University Childrens Hospital, Magdeburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Vorwerk
authors.affiliation: Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Wilop
authors.affiliation: Radiologie München, Burgstraße 7, München, Germany.
authors.forename: H A
authors.initials: HA
authors.lastname: Wolff
authors.affiliation: Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University , Aachen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Mertens
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis; D002648:Child; D003131:Combined Modality Therapy; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009305:Nasopharynx / Q000473:pathology; D009367:Neoplasm Staging; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral