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.

Prognosis of nasopharyngeal carcinoma with insufficient radical dose to the primary site in the intensity‐modulated radiotherapy era

“…Although some studies have reported that reduced radiation therapy is feasible for children and adolescents with NPC-and HPV-positive oropharyngeal cancer, 8,9,11,17,18 it is unclear whether reduced-dose radiation for adults with NPC with IMRT can achieve satisfactory results. Although some studies have reported that reduced radiation therapy is feasible for children and adolescents with NPC-and HPV-positive oropharyngeal cancer, 8,9,11,17,18 it is unclear whether reduced-dose radiation for adults with NPC with IMRT can achieve satisfactory results.…”

“…NPC-and HPVpositive oropharyngeal cancer are both virus-related tumors and are sensitive to radiotherapy and chemotherapy. 17 Based on this previous research, the team conducted another clinical trial (NPC-2003-GPOH/DCOG) to study the effect of an even lower radiation dose. 11 Fortyfour patients with complete or partial remission to IC received chemoradiotherapy with 54 Gy radiation doses.…”

“…Based on these studies of reduced-dose radiotherapy on children and adolescents [8][9][10]17 and our data, it is necessary to carry out a phase II clinical trial to demonstrate the feasibility of reduced-dose radiotherapy for NPC with good tumor regression during IC. Although some studies have been demonstrated the feasibility of reduced-dose radiotherapy based on IC, 11,18,26 reduced-dose radiation for newly diagnosed patients without metastasis may be overaggressive.…”

“…NPC is associated with the infection of EBV and is sensitive to radiotherapy. Although some studies have reported that reduced radiation therapy is feasible for children and adolescents with NPC-and HPV-positive oropharyngeal cancer, 8,9,11,17,18 it is unclear whether reduced-dose radiation for adults with NPC with IMRT can achieve satisfactory results. Here, we performed a study that retrospectively analyzed the outcome of patients who did not complete the standard radiation dose for different reasons.…”

“…The 9-year OS and disease-free survival were 95% and 91%, respectively. 17 Based on this previous research, the team conducted another clinical trial (NPC-2003-GPOH/DCOG) to study the effect of an even lower radiation dose. Fifty-five patients with stage III/IV disease received three courses of IC with cisplatin, 5-fluorouracil, and folinic acid.…”