Undifferentiated Carcinoma Of Nasopharyngeal Type Research Articles

Long term disease-free survival in locoregional, metastatic and/or recurrent UCNT.

e18023 Background: Undifferentiated Carcinoma of Nasopharyngeal Type (UCNT) is a rare and aggressive type of head and neck cancer related to the Epstein Barr virus (EBV), genetic (HLA B5 in Algeria) and environmental factors. It is the most frequent histological variant of ENT cancers. It has geographically selective epidemiologic features unrelated to external carcinogens, and is known to be radiosensitive and chemosensitive. Methods: Seventy-one patients with biopsy-proven UCNT presenting to a single oncology unit between 2015 and 2022 were assessed for their long-term response to treatment. The sex ratio of cases was 3M: 1F; thirty-one patients (43%) were under the age of 50; 11 (15%) under the age of 35; and among these, there were two 19 year old males. The initial median World Health Organization (WHO) performance status was 1.6. These patients with locoregional (LR), recurrent (REC) and/or metastatic (MTS) UCNT were treated with monthly cycles of platinum-based chemotherapy of cisplatin (CDDP) 75 mg/m2 IV or Carboplatine AUC-4 and Docetaxel 75 mg/m2 IV followed by fluorouracil (5FU) 1000 mg/m2/day continuous IV infusion days 1 to 4 (TPF) in locally advanced disease, and with cisplatin (CDDP) 75 mg/m2 day 1 or Carboplatine AUC-5; and fluorouracil (5FU) 1000 mg/m2/d continuous IV infusion days 1 to 4 (PF) in recurrent and/or metastatic cases. The choice of systemic therapy was individualized based on patient characteristics including performance status, goals of therapy. Results: Those LR or MTS patients who were still alive without evidence of disease after 36+ months were categorized as complete responders (CRs). A subgroup of CRs was identified who had failed prior chemotherapy. MTS patients with less than three distant osseous sites underwent additional radiation therapy. Conclusions: Encouraging results for this particular type of head and neck cancer confirm the chemosensitivity of UCNT, and the observation of long-term responders makes curability a real consideration.

Effect of LMP-1 and mutant p53 on the Prognosis of Undifferentiated Type of Nasopharyngeal Carcinoma

Undifferentiated carcinoma is a subtype of NPC with a higher EBV antibody titer than healthy people. The carcinogenic effect of EBV involves LMP-1 associated with poor prognosis, and mutant p53 predicts tumor recurrence. This study aims to assess the effect of LMP-1 and mutant p53 on the prognosis of NPC patients. 40 paraffin blocks were stained with LMP-1 and p53 mutant. LMP-1 was positive when the cytoplasm and tumor cell membranes were brown, and mutant p53 was positive for the brown tumor cell nucleus. Pearson correlation test was performed. Most respondents were in the age group 40 years, males, regional lymph node involvement (N) in group N1, and no metastasis (M). The expression levels of LMP-1 and mutant p53 were strongly positive. The study showed the correlation between LMP-1 with age (p 0.327), gender (p 0.599), category N (p 0.512), category M (p 0.019) and the correlation between mutant p53 with age (p 0.329), gender (p 0.981), category N (p 0.013), category M (p 0.705). LMP-1 expression with mutant p53 (p 0.760). It can be concluded that LMP-1 and mutant p53 could be used as prognostic factors in NPC patients.

Total thymectomy for thymic lymphoepithelioma-like carcinoma\u2014report of two cases

BackgroundThymic carcinoma has been classified into 12 subtypes, thymic lymphoepithelioma-like carcinoma (LELC) is a type of them, and has a pathological organization similar to that of lymphoepithelioma, an undifferentiated type of nasopharyngeal carcinoma. According to a report from the International Thymic Malignancy Interest Group (ITMIG), thymic LELC is a rare tumor and accounts for 6% of all thymic carcinoma cases. We report two cases of surgical resection for thymic LELC and perform a search of other reports of thymic LELC, and clinical manifestations and follow-up data thus obtained are summarized.Case presentationTwo patients underwent surgical resection for thymic LELC. In both, tumors were detected in the anterior mediastinum and a total thymectomy was performed. Each was diagnosed with thymic LELC and classified in accordance with the Masaoka staging system as modified stage II. In recent examinations, one patient was doing well after undergoing total resection, whereas early recurrence of distant lymph node metastasis was noted in the other at 5 months after the total resection procedure and died thereafter from a different disease.ConclusionWe report two cases of surgical resection for thymic LELC. A successful total resection may positively affect prognosis: thus, long-term follow-up examinations must be performed.

THE RELATION OF EBNA-1 AND EGFR EXPRESSION SCREENING FROM ADVANCED STAGE UNDIFFERENTIATED NASOPHARYNGEAL CANCER

Introduction:
 Nasopharyngeal carcinoma (NPC) is a lymphoepithelial malignancy of the nasopharynx, one of the etiologies is the infection of Epstein–Barr virus in undifferentiated type of nasopharyngeal carcinoma. The Epstein-Barr virus Nucleus Antigen-1 (EBNA-1) is Epstein–Barr virus-encoded proteins as regulatory virus transcription. Epithelial Growth Factor Receptor (EGFR) consist of a single polypeptide chain of amino acid, ErbB members, tyrosine kinase receptor, a transmembrane glycoprotein encoded by gen location in the short arms of a chromosome and overexpression in epithelial tumors. EGFR plays a central role in signal transduction pathways which regulate key cellular functions in epithelial malignancies. and may also present in NPC.
 Objective:
 To investigate this relation of expression patterns of EBNA-1 and EGFR in a histological type of undifferentiated nasopharyngeal carcinoma.
 Method:
 Observational, analytical study with a cross-sectional method of 34 formalin-fixed within inclusion criteria are EBNA-1 and positive staining of EGFR expression (30 patients) and exclusion criteria of negative staining of EGFR (4 patients). All biopsy samples work with paraffin embedded and resulted in hematoxylin-eosin undifferentiated histological types of the advanced stage in nasopharyngeal carcinoma. EBNA-1 and EGFR expression used immunohistochemistry staining.
 Result:
 EBNA-1 and EGFR expression level were detection and correlated with the advanced stadium of nasopharyngeal undifferentiated carcinoma.
 Conclusion: 
 EBNA-1 is significantly related to EGFR expression in the advanced stadium of undifferentiated nasopharyngeal carcinoma. Overexpression of EGFR is mostly found in advanced NPC but not in all ages. Male is dominated and overall age below 55 years old. Screening of EGFR with immunohistochemistry is highly considered before anti-EGFR treatment

The sequence analysis of Epstein-Barr virus EBNA1 gene: could viral screening markers for nasopharyngeal carcinoma be identified?

Epstein-Barr virus (EBV) has been identified as a group 1 carcinogenic agent, particularly for nasopharyngeal carcinoma (NPC). The sequence diversity of EBV nuclear antigen 1 (EBNA1) reflects region-restricted polymorphisms, which may be associated with the development of certain malignancies. The aims of the present study were to evaluate EBV EBNA1 gene polymorphisms circulating in NPC, infectious mononucleosis, and isolates from patients with transplanted organs to determine if EBNA1 sequence specificities are useful as viral biomarkers for NPC. Forty biopsies of undifferentiated carcinoma of nasopharyngeal type (UCNT), 31 plasma samples from patients with mononucleosis syndrome, and 16 plasma samples from patients after renal transplantation were tested in this study. The EBNA1 gene was amplified by nested PCR. Further investigation included sequencing, phylogenetic, and statistical evaluations. Eighty-seven sequences were identified as one of the four EBNA1 subtypes, P-Ala, P-Thr, V-Val, and V-Ala, with further classification into ten subvariants. Of these, P-Thr-sv-1 and P-Thr-sv-3 have never been identified in Europe, while V-Val-sv-1 was newly discovered. Statistical analysis revealed significant differences in the distribution of EBNA1 P-Thr subvariants between the three groups of patients, with noticeable clustering of P-Thr-sv-5 in NPC isolates (p < 0.001). EBV EBNA1 showed no sequence specificity in primary infection. This research revealed a newly discovered EBNA1 subvariant. Importantly, EBNA1 P-Thr-sv-5 showed carcinoma-specific EBNA1 variability. Thus, identification of this subvariant should be considered as a viral screening marker for NPC or UCNT.

Cigarette smoking and the risk of nasopharyngeal carcinoma: a meta-analysis of epidemiological studies

ObjectiveThe role of cigarette smoking as an independent risk factor for patients with nasopharyngeal carcinoma (NPC) is controversial. We attempted to provide evidence of a reliable association between cigarette smoking...

Undifferentiated carcinoma of nasopharyngeal type in children: Clinical features and outcome

ObjectivesTo describe the epidemiology, clinical features and treatment of undifferentiated carcinoma of nasopharyngeal type in children. Material and methodsRetrospective study of 40 patients under the age of 17 years managed for undifferentiated carcinoma of nasopharyngeal type in two oncology centres in the central region of Tunisia between 1995 and 2012. ResultsPatients had a median age of 14 years with a sex ratio of 1.3. The mean time to presentation was 5 months. The presenting complaint was cervical lymphadenopathy in 90% of cases. Thirty-seven patients received curative treatment, according to a sequential mode in 85% of cases, starting with chemotherapy followed by radiotherapy to the nasopharynx and cervical lymph nodes. The median dose delivered to the nasopharynx was 70.4Gy. Two cases of local recurrence and five cases of metastatic relapse (all involving bone), were observed during follow-up. After a mean follow-up of 80.5 months (range: 1 to 180), 29 patients (72.5%) were in complete remission, eight had died and three were lost to follow-up. The 5-year overall survival was 77.7%. ConclusionUndifferentiated carcinoma of nasopharyngeal type in children represents 6% of all cases of UCNT managed in our institutions. It is often discovered at an advanced stage. Sequential treatment combining chemotherapy and radiotherapy achieves an excellent local control rate.

Characterization of the Variability of Epstein-Barr Virus Genes in Nasopharyngeal Biopsies: Potential Predictors for Carcinoma Progression.

Epstein-Barr virus (EBV) infection is a significant factor in the pathogenesis of nasopharyngeal carcinoma, especially in the undifferentiated carcinoma of nasopharyngeal type (UCNT, World Health Organization type III), which is the dominant histopathological type in high-risk areas. The major EBV oncogene is latent membrane protein 1 (LMP1). LMP1 gene shows variability with different tumorigenic and immunogenic potentials. EBV nuclear antigen 1 (EBNA1) regulates progression of EBV-related tumors; however, the influence of EBNA1 sequence variability on tumor pathogenesis is controversial. The aims of this study were to characterize polymorphisms of EBV genes in non-endemic nasopharyngeal carcinoma biopsies and to investigate potential sequence patterns that correlate with the clinical presentation of nasopharyngeal carcinoma. In total, 116 tumor biopsies of undifferentiated carcinoma of nasopharyngeal type (UCNT), collected from 2008 to 2014, were evaluated in this study. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. The presence of EBV DNA was significantly distributed between TNM stages. LMP1 variability showed six variants, with the detection of the first China1 and North Carolina variants in European nasopharyngeal carcinoma biopsies. Newly discovered variants Srb1 and Srb2 were UCNT-specific LMP1 polymorphisms. The B95-8 and North Carolina variants are possible predictors for favorable TNM stages. In contrast, deletions in LMP1 are possible risk factors for the most disfavorable TNM stage, independent of EBNA2 or EBNA1 variability. A newly discovered EBNA1 subvariant, P-thr-sv-5, could be a potential diagnostic marker, as it represented a UCNT-specific EBNA1 subvariant. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, type 1/Med/P-thr was identified as a possible risk factor for TNM stage IVB or progression to the N3 stage.

A open label phase II trial of cetuximab plus cisplatin in patients with recurrent or metastatic undifferentiated carcinoma of nasopharyngeal type: Results after three years.

e17021 Background: To evaluate efficacy and toxicity of cetuximab plus cisplatin in recurrent or metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT) after previous platinum based ch...

Endoscopic Endonasal Transpterygoid Transmaxillary Approach to the Infratemporal and Upper Parapharyngeal Tumors

To describe the endoscopic transnasal approach to the infratemporal fossa (ITF) and upper parapharyngeal space (UPS) and to analyze the indications and outcomes of this surgical technique in the management of the tumors localized in this critical area. Case series with chart review. Tertiary-care referral center. Retrospective review of patients with benign and malignant tumors arising in or extending to the ITF and UPS, treated from 2002 to 2012 at a single institute. The tumors were surgically resected using an endoscopic endonasal transpterygoid transmaxillary approach. Thirty-seven consecutive patients with benign tumors (20 juvenile nasopharyngeal angiofibromas, 2 extracranial trigeminal Schwannomas, 2 meningiomas, 1 cavernous hemangioma) and nonmetastatic malignant tumors (2 adenoid-cystic carcinoma, 1 mucoepidermoid carcinoma, 1 squamous cell carcinoma, 1 adenocarcinoma, 1 recurrence of chondrosarcoma, and 6 recurrences of undifferentiated carcinoma of nasopharyngeal type) were treated with curative intent. A gross-total resection was achieved in 35 of 37 patients. Major complications were observed in 1 case (intraoperative internal carotid artery blowout). Postoperatively, 8 patients received some form of adjuvant treatment. Mean follow-up was 30 months for malignancies and 60 months for benign tumors. All patients are now alive without recurrences. Stable intracranial persistence of disease was reported in 2 cases (1 meningioma and 1 adenoid-cystic carcinoma). The purely endoscopic endonasal technique may provide a minimally invasive and safe approach to radically resect selected tumors involving the ITF and UPS. Larger case series and longer follow-up are needed to validate the reproducibility and efficacy of this technique.

Efficient Immortalization of Primary Nasopharyngeal Epithelial Cells for EBV Infection Study

Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.

A phase II trial of induction chemotherapy with cisplatin, docetaxel, and capecitabine followed by concurrent cisplatin-radiotherapy in advanced nasopharyngeal carcinoma.

5543 Background: The purpose of this study is to assess the antitumor activity and toxicity of a induction chemotherapy regimen combining docetaxel (T), cisplatin (C) and capecitabine (X) followed by concurrent chemoradiotherapy in advanced nasopharyngeal carcinoma. Methods: Previously untreated patients (pts) with histologically diagnosed locally advanced nasopharyngeal carcinoma (Stages IVA and IVB, III TNM/UICC 2002) received T 75 mg/m2, P 75 mg/m2 both on day 1 and X 1000 mg/m²/d, days 1-14, with cycles repeated every 3 weeks. All pts received four cycles in a neoadjuvant setting before concurrent C 75 mg/m² day 1, 22, 42 and radiotherapy (4 to 6 weeks after the third cycle of PTX). Pts were evaluated by clinical examination, CT scan of the nasopharynx, the primary end point was tumor response. Results: 89 pts (64 male and 25 female) were enrolled. Median age was 45 years (range 18-67), ECOG performance status was 0-1 in all pts. 68 pts (76%) had an undifferentiated carcinoma of nasopharyngeal type (UCNT) and 21 pts (24%) a poorly differentiated nasopharyngeal carcinoma. 18 pts had stage III disease, 35 pts stage IVA disease and 36 pts stage IVB. Toxicity and tumor response were assessable in 89 pts. After 344 cycles, grade 3-4 toxicities (NCI-CTC 3.0) were: neutropenia (18 %), anemia (10.5%), nausea and vomiting (28%), diarrhea (8%), mucositis (3%), reversible alopecia (100%) and fatigue (10%). No febrile neutropenia was noted. 2 pts had G3 renal toxicity and only one patient had hand-foot syndrome. Response rates for the 89 pts were: complete response 48%, partial response 49% and stable disease 3%. All pts had a complete response after radiotherapy. The disease free survival (DFS) and overall survival at two years was respectively 78 % and 83 %. Conclusions: PTX induction chemotherapy resulted on a high response rate with manageable toxicity. This results need to be confronted with DFS and overall survival after longer follow-up.

Determinants of severe oral mucositis in paediatric cancer patients: a prospective study

To analyse the incidence and the determinants of severe oral mucositis (OM) in young cancer patients treated by standard chemotherapy. The study was carried out at the Pediatric Hemato-Oncology unit of Children's Hospital of Rabat. Patients under 16 years of age with malignant disease treated by chemotherapy between January 2001 and December 2006 were recorded. Consecutive patients (n = 970) with malignant disease were studied. The age ranges from 2 months to 16 years (mean, 6.8 ± 4.1 years). OM occurred in 540 (55.6%) patients, and 17.9% of them encountered severe grades. Mean time to onset of the lesions was 10.5 ± 6.8 (range, 1-22 days) and mean duration was 6.8 ± 3.1 (range, 2-23 days). All chemotherapeutic protocols were associated with OM development (range, 20-100%). Patients with severe OM were more likely to have undifferentiated carcinoma of nasopharyngeal type (RR = 2.6, 95% IC 1.1-6.1), non-Hodgkin lymphoma (RR = 2.1, 95% CI 1.2-2.4) and acute leukaemia (RR = 1.7, 95% CI 1.5-3.6). Methotrexate-based therapies were also associated with the worsening of OM (RR = 1.7, 95% IC 1.2-2.6). Underlying disease and chemotherapy regimens are the principal risk factors of OM development. This model can help in the identification of patients at risk for adequate preventive and therapeutic measures.

Undifferentiated carcinoma of nasopharyngeal type (UCNT): a Swiss single-institutional experience during 1990-2005.

Nasopharyngeal carcinoma is a rare tumor entity in Switzerland. In contrast, it is endemic in Asian and African countries. Retrospective studies have been conducted in order to identify risk factors and prognostic determinants of nasopharyngeal carcinoma. Nonetheless, these trials were mostly conducted in regions with high prevalence for the disease and little is known about the risk factors and prognosis of nasopharyngeal carcinoma for a non-endemic population in Western Europe. This retrospective trial was conducted to identify risk factors and prognostic determinants of nasopharyngeal carcinoma for a non-endemic population in Switzerland. Overall survival was 91%, 77% and 58% for one, three and five years, respectively. Factors with favourable prognostic value were concomitant radiochemotherapy regimens, photon radiotherapy, and a delay between diagnosis and first therapy session of less than ten weeks, respectively. Factors with unfavourable prognostic values were age over 65 years at time of diagnosis and nasopharyngeal carcinoma of WHO type I. Risk factors, biological behaviour and survival are well comparable between endemic and non-endemic populations for nasopharyngeal carcinoma. Nonetheless, an aggressive diagnostic procedure and sophisticated interdisciplinary therapy are indispensable in order to achieve favourable outcome. Therefore, diagnosis and therapy of nasopharyngeal carcinoma in non-endemic populations should be limited to highly specialized tertiary centres.

Undifferentiated carcinoma of nasopharyngeal type (UCNT): a Swiss single-institutional experience during 1990-2005.

Nasopharyngeal carcinoma is a rare tumor entity in Switzerland. In contrast, it is endemic in Asian and African countries. Retrospective studies have been conducted in order to identify risk factors and prognostic determinants of nasopharyngeal carcinoma. Nonetheless, these trials were mostly conducted in regions with high prevalence for the disease and little is known about the risk factors and prognosis of nasopharyngeal carcinoma for a non-endemic population in Western Europe. This retrospective trial was conducted to identify risk factors and prognostic determinants of nasopharyngeal carcinoma for a non-endemic population in Switzerland. Overall survival was 91%, 77% and 58% for one, three and five years, respectively. Factors with favourable prognostic value were concomitant radiochemotherapy regimens, photon radiotherapy, and a delay between diagnosis and first therapy session of less than ten weeks, respectively. Factors with unfavourable prognostic values were age over 65 years at time of diagnosis and nasopharyngeal carcinoma of WHO type I. Risk factors, biological behaviour and survival are well comparable between endemic and non-endemic populations for nasopharyngeal carcinoma. Nonetheless, an aggressive diagnostic procedure and sophisticated interdisciplinary therapy are indispensable in order to achieve favourable outcome. Therefore, diagnosis and therapy of nasopharyngeal carcinoma in non-endemic populations should be limited to highly specialized tertiary centres.

Prognostic significance of clinical parameters and Epstein-Barr virus infection in non-endemic undifferentiated carcinoma of nasopharyngeal type: a Serbian report

Undifferentiated carcinoma of nasopharyngeal type (UCNT) is very rare tumour in Serbia, like in most of the countries of Europe, with incidence less than 0.5 per 100,000 people per year. The aim of this study was to assess the presence of Epstein-Barr virus (EBV) in the UCNT of a non-endemic population in Serbia and identify the main clinical parameters that interfere with patients' survival rate. This study included 102 patients with UCNT who were diagnosed between 1996 and 2003. Biopsies were analysed for EBV-encoded RNA (EBER) by in situ hybridization of tumour tissue microarray. Of 102 patients, 76 were men and 26 were women with ages ranging between 18 and 82 years (median 52.5, mean 53.0±14.1). Survival rates were 80, 39 and 31% for one, three and five years, respectively. Ninety-three of 102 cases were EBER positive (92%). Factors with unfavourable prognostic values were age over 50 years at the time of diagnosis, advanced clinical stage, therapy other than chemoradiotherapy and EBER negative status. In regard to the clinical data, EBER expression in UCNT was shown to be a strong independent predictor of overall and progression-free survival. To our knowledge, the current report constitutes the largest European non-endemic series of UCNT samples from a single institution with correlation between survival and clinical parameters/EBER status.

Actualités des traitements médicaux des cancers du nasopharynx

Nasopharyngeal carcinomas (NPC) are predominantly of undifferentiated type (UCNT or undifferentiated carcinoma of nasopharyngeal type), rare (< 1/100000) and sporadic in occidental countries, but endemic in the Mediterranean area of intermediate incidence (2 to 10/100000) and highly frequent (> 10/100000) in South East Asia. NPC staging is based on TNM UICC 2002 that has a prognostic and therapeutic orientation impact. Irradiation of the primitive tumor and its extensions remains the standard loco-regional treatment. The recent introduction of primary and concomitant chemotherapy leads to an improvement in terms of overall and disease-free survival, specially for for high-risk-patients (T3-4 and N2-3 disease). Prognosis remain linked to T, N, histologic type and quality of response to chemotherapy and radiotherapy.

Les cancers du cavum juvéniles : aspects anatomocliniques, biologiques, thérapeutiques et évolutifs

Nasopharyngeal carcinoma (NPC) represents one of the most frequent epithelial tumours of the child in intermediate risk regions. In the Maghreb, it represents the first cancer of teenagers of 15-20 years old. The Epstein Barr virus (EBV) is the most important etiologic factor. Its role in the pathogeneses of NPC has been confirmed by several studies. Young NPCs are characterized by a low rate of EBV antibodies and a high level of LMP1 cell expression than in adult’s NPC. The undifferentiated carcinoma nasopharyngeal type (UCNT) represents the most frequent histological type. Immunohistochimical analyses of North Africa early onset NPC is characterized by a weak expression of bcl-2 and p53 and a strong expression of LMP1 and c-kit what makes them different from the adult’s NPC. Clinically, cervical node involvement is constantly present. Juvenile NPC is characterized by a very important locoregional extension as well as a high rate of distant metastases. More than 15% of patients had metastases at diagnosis. Radiotherapy is still the standard therapy of NPC. Only some retrospectives studies have been published to determine the benefit, the type and the timing of the chemotherapy in the treatment of juvenile NPC. Metastatic relapses constitute the main cause of death at these youngpatients. An improvement of the prognosis canbewaited with concomitant chemotherapy and intensity modulated radiotherapy. However, randomized multi institutional studies are necessary to standardize the treatment of the NPC in childhood.

Risk factors for the occurrence of undifferentiated carcinoma of nasopharyngeal type: A case-control study

The incidence rate of nasopharyngeal carcinoma in Serbia is less than one per 100,000 citizens, which classifies it as a region with low incidence for this disease. The aim of this study was to test some hypotheses of the risk factors for undifferentiated carcinoma of nasopharyngeal type (UCNT) in the low incidence population. A case-control study was used for the research. The study included 45 cases with histopathological diagnosis of UCNT and 90 controls. Cases and the controls were individually matched by sex, age (+/- 3 years), and place of residence (city-village). Data were gathered about sociodemographic characteristics, occupational exposure to harmful agents, habits, diet, personal history, and family history. In the analysis of the data, conditional univariate and multivariate logistic regression analyses were applied. According to the results of multivariate logistic regression analysis UCNT was significantly positively associated with "passive smoking" of tobacco in the family during childhood, frequent consumption of industrially manufactured food additives for enhancing flavour and frequent consumption of white bread. UCNT was significantly negatively associated with frequent consumption of margarine, olive oil and cornbread. In our low incidence population, an independent risk factor for the occurrence of UCNT was "passive smoking" of tobacco in the family during childhood, use of industrially manufactured food with additives for enhancing flavour and consumption of white bread. Multicentric study enrolling a greater number of cases would be desirable.

Phase II trial of combination docetaxel and cisplatin in patients with locally advanced nasopharyngeal carcinoma

6044 Background: The standard treatment of locally advanced nasopharyngeal carcinoma is cisplatin-based chemotherapy followed by locoregional radiotherapy. The purpose of this study is to assess the antitumor activity and toxicity of a new neoadjuvant chemotherapy regimen combining docetaxel (D) and cisplatin (C). Methods: Previously untreated patients (pts) with histologically diagnosed locally advanced nasopharyngeal carcinoma (stages IVA and IVB, TNM/UICC 1997) received D 75 mg/m2 and C 75 mg/m2 both on day 1, with cycles repeated every 21 days. All pts received three cycles in a neoadjuvant setting before radiotherapy (4 to 6 weeks after the third cycle of DC, 65–70 Gy 5 fractions/week). Pts were evaluated by clinical examination, CT scan of the nasopharynx, and nasofibroscopy with biopsy. The primary end point was tumor response. Secondary end points were disease-free survival (DFS), toxicity, and overall survival (OS). Results: 93 pts (65 male, 28 female) were enrolled. Median age was 42 years (range 18–69), WHO performance status was 0–1 in 87 pts and 2 in 6 pts. 75 pts (81%) had an undifferentiated carcinoma of nasopharyngeal type (UCNT) and 18 pts (19%) a differenciated carcinoma of the nasopharynx. 31 pts had stage IVA disease and 62 pts had stage IVB. Toxicity, tumor response, and survival at 5 years (median follow up 49.5 months) were assessable in 90 pts. After 270 cycles, grade 3–4 toxicities (WHO) were: neutropenia (12 %), febrile neutropenia (2%), anemia (1%), nausea and vomiting (23%), diarrhea (8%), mucositis (1%), reversible alopecia (70%). Two pts had onycholysis. Response rates for the 90 pts were: complete response 32.2% (29 pts), partial response 54.4% (49 pts), stable disease 11.1% (10 pts), and progressive disease 2.2% (2 pts). The overall response rate (ORR) was 86.6% and 89% amongst the UCNT. After radiotherapy, 88 pts had a complete response and one patient had stable disease. DFS and OS at 5 years were 52% and 55%, respectively. Conclusions: DC chemotherapy followed by radiation therapy is an effective regimen for the treatment of advanced UCNT and has an acceptable safety profile. These data need to be compared with concurrent chemoradiotherapy to assess the best strategy for the management of advanced UCNT. No significant financial relationships to disclose.