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.

Zusammenfassung

Das Nasopharynxkarzinom (NPC) ist ein seltener maligner Tumor, der aus Epithelzellen des Nasopharynx hervorgeht. Der Tumor tritt am häufigsten in Südostasien auf und zeigt einen Altersgipfel in der Adoleszenz und einen zweiten im Alter zwischen 55–59 Jahren. Dem Epstein-Barr-Virus (EBV) kommt eine Schlüsselfunktion bei der Entstehung des NPC zu, dazu kommen Umweltfaktoren, wie die Aufnahme Nitrosamin-haltiger Speisen und bestimmte genetische Polymorphismen. Bei Erstdiagnose sind bis zu 90% der Tumoren bereits lymphogen metastasiert, bei 5–10% lassen sich Fernmetastasen feststellen. Die Diagnose des NPC erfolgt histologisch und wird durch eine abnorme IgA-Immunantwort gegen EBV-VCA und den Nachweis einer hohen Plasma EBV-DNA-Last gestützt. Die besten Behandlungsergebnisse bei Kindern und Jugendlichen mit fortgeschrittenem lokoregionären Befall, mit Gesamt- und Ereignis-freien Überlebensraten>90% wurden durch eine neoadjuvante Chemotherapie, gefolgt von einer Radiochemotherapie und anschließender Erhaltungstherapie mit Interferon-ß erreicht, wie in den GPOH-Studien NPC-91 und 2003 dargestellt. Da der Großteil von Spätkomplikationen wie Xerostomie und Haut- und Gewebsfibrose auf hohe Strahlendosen zurückzuführen ist, sollten bei der Strahlentherapie Verfahren wie die Intensitäts-modulierte Strahlentherapie eingesetzt werden, um die Streustrahlung auf gesundes Gewebe in der Tumorumgebung zu minimieren. Die Heilungsaussichten für Patienten mit Fernmetastasen und einem Rezidiv sind gering. Hier sollten neue Behandlungsverfahren wie die Gabe EBV-spezifischer T-Zellen zur Anwendung kommen.

Key words

nasopharyngeal cancer - children - adolescents - therapy - interferon - chemotherapy

Schlüsselwörter

Nasopharynxkarzinom - Kinder - Jugendliche - Therapie - Interferon - Chemotherapie

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