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Purpose: Radiation therapy with chemotherapy (CCR) is currently the gold standard treatment for nasopharyngeal carcinoma (NPC). Anatomical changes are mainly due to weight loss. Our prospective study aimed to evaluate the nutritional status and the quality of weight loss in our patients to adapt the subsequent nutritional management of patients during treatment for NPC., Patients and Methods: A prospective, single-center study of 27 patients with non-metastatic NPC treated in our oncology radiotherapy department between August 2020 and March 2021. Data from interrogation, physical examination, and bioelectrical impedancemetry (weight [W], body mass index [BMI], fat index [GI], fat mass [FM], and fat-free mass (FFM]) were collected at the beginning, the mid, and the end of treatment., Results: Weight loss from mid to end of treatment (median=-4kg [-9.4; -0.9]) was greater than that from baseline to mid-treatment (median=-2.9kg [-8.8; 1.8]) (P=0.016). Weight loss during the entire treatment was -6.2kg [-15.6; -2.5] (8.4%). The losses of FM were identical between the beginning-mid treatment and the mid-end treatment; they were respectively -1.4kg [-8.5; 4.2] and -1.4kg [-8.2; 7.8] (P=0.4). FFM losses between the mid- and the end of treatment (-2.5kg [-27.8; 0.5]) were greater than those between baseline and mid-treatment (-1.1kg [-7.1; 4.7]) (P=0.014). Median FFM loss during treatment was -3.6kg [-28.1; 2.6])., Conclusion: The results of our study show that weight loss during CCR for NPC is complex and is not just about loss but about a disruption of body composition. Regular follow-ups by nutritionists are required to prevent denutrition during treatment., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Nasopharyngeal carcinoma diagnosis is often made at a locally advanced stage (75 to 90% of cases) due to its deep localization. Concomitant radio-chemotherapy is the cornerstone of the treatment of locally advanced forms. The advent of intensity-modulated radiotherapy has improved oncological outcomes and reduced toxicity and is currently the gold standard for irradiation technique. For the locally advanced stage, the addition of induction chemotherapy has become the new standard care according to the latest international recommendations to reduce tumor volumes and act early on micro-metastases. Despite these therapeutic advances, the local and especially distant failure rate remains high. This article reviews current treatment strategies and discuss new approaches and perspectives of locoregional and systemic treatment to reduce treatment failures., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The pre- and post-induction chemotherapy tumor volumes of nasopharyngeal carcinomas may be prognostic indicators for adapting the therapeutic strategy. The objective of our study is to assess the prognostic impact of pre- and post-induction chemotherapy volumes in patients treated for locally advanced nasopharyngeal carcinomas., Patients and Methods: This is a retrospective study including 52 patients with locally advanced nasopharyngeal carcinoma treated with 3 courses of induction chemotherapy (TPF) followed by intensity modulated radiotherapy associated with concomitant chemotherapy., Results: The median initial and post induction chemotherapy total volumes were 92.3 and 41.5mL, respectively. At 3 years, the LRFS, DMFS, DFS and OS were respectively 85.9%, 63.5%, 56.8% and 67.8%. In multivariate study, the combination of a high initial volume (>100mL) and post-chemotherapy volume (>35mL) was an independent factor for LRFS, DMFS, DFS and OS. The total baseline volume had a better predictive prognostic value for DFS and OS than the TNM classification (8th edition 2017)., Conclusion: The prognostic weight of tumor and nodal volumes was greater than the TNM classification (8th edition). The pre- and post-chemotherapy tumor volumes allow selecting a high-risk patients' subgroup "high initial and post chemotherapy volumes" in which it would be advisable to offer more intensive treatment regimens., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Nasopharyngeal carcinoma has the highest metastatic potential of all head and neck cancers. The survival time of patients with nasopharyngeal carcinoma has improved significantly in the last decades due to the use of combination of chemotherapy and radiotherapy, as well as advances in radiotherapy techniques. However, appropriately 30% of patients with nasopharyngeal carcinoma suffer a poor prognosis, mainly due to distant metastasis., Objective: The study aimed to identify the survival and prognostic factors in metastatic nasopharyngeal carcinoma., Methods: A retrospective analysis was conducted in patients treated for synchronous metastatic nasopharyngeal carcinoma or metachronous metastatic nasopharyngeal carcinoma for 14 years (2003-2016). Overall survival was analyzed using the Kaplan-Meier method and compared using the log-rank test for the whole population and both groups of patients. Multivariate analysis was performed using the Cox model; p-values < 0.05 were considered to indicate statistical significance., Results: One hundred and twelve patients with metastatic nasopharyngeal carcinoma were included (51 patients with metastatic nasopharyngeal carcinoma, and 61 patients with metachronous metastatic nasopharyngeal carcinoma). In the whole population, the median overall survival was 10 months (1-156 months). In the multivariate analysis, female gender, poor performance status (WHO > 1) and metachronous metastasis were independent prognostic factors. In the metastatic nasopharyngeal carcinoma patients, the median overall survival was 13 months (1-156 months). In multivariate analysis, independent prognostic factors were non-oligometastatic disease, severe (G3‒G4) chemotherapy toxicity and the lack of nasopharyngeal and metastatic site irradiation. In the metachronous metastatic nasopharyngeal carcinoma patients, the median overall survival was 7 months (1-41 months). In multivariate analysis, the poor performance status (WHO > 1) was an independent metastatic nasopharyngeal carcinoma prognostic factor., Conclusion: Oligometastatic patients with synchronous metastatic nasopharyngeal carcinoma had better survival. The locoregional treatment of primitive nasopharyngeal carcinoma improved survival in patients with metastatic nasopharyngeal carcinoma who responded to induction chemotherapy. Local irradiation of metastatic sites improved survival of metastatic nasopharyngeal carcinoma patients. Grade 3 or 4 chemotherapy toxicity altered survival among patients with synchronous metastatic nasopharyngeal carcinoma., (Copyright © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Objectives: The study aimed to investigate the epidemiological and clinical characteristics as well as the therapeutic results in patients with locoregional (LR) relapse after treatment of nasopharyngeal carcinoma (NPC)., Methods: We retrospectively reviewed the medical records of patients with local and/or regional recurrent NPC over 13 years (2003-2015)., Results: Twenty-five patients were treated for local or/and local-regional recurrence of NPC. The rate of LR relapse was 7.2%. The mean age of the patients was 46 ± 13.9 years. The median time to relapse was 25 months. The recurrence was nasopharyngeal in 17 patients, nasopharyngeal and neck lymph nodes in 7 patients, and neck lymph nodes in 1 patient. Fifteen relapsed patients had a locally advanced disease (rT3-rT4). Patients who had initially T1 or T2 tumor had a locally advanced relapsed disease (rT3rT4) in 27.3% and patients whose disease was initially classified as T3 or T4 had a locally advanced relapsed disease (rT3T4) in 85.7% ( P = .005, Fisher test). Twelve patients had chemotherapy after relapse. Chemotherapy was followed by concurrent chemoradiotherapy in 3 patients and by radiotherapy (RT) in 4 patients. Nine patients had concurrent chemoradiotherapy and 1 patient had exclusive RT. The overall survival (OS) at 1 year, 3 years, and 5 years was, respectively, 58%, 18%, and 10%. The OS was significantly higher in patients with good performance status at the time of relapse (World Health Organization = 1; P = .01) and in patients with late relapse (after 2 years; P = .03)., Conclusions: Locoregional relapse rate in our study was 7.2%. Locoregional reirradiation was the mainstay treatment modality in relapsed NPC. Relapsed NPC had a poor prognosis with a 5-year survival rate of 18%. The OS was significantly higher in patients with good performance status and in patients with late relapse (after 2 years).

Modern high-precision radiotherapy techniques have recently incorporated the notion of anatomical variations of the patient during treatment and have tried to adapt the treatment planning to them. Adaptive radiotherapy for nasopharyngeal tumors is starting to prove its benefit nowadays. His interest is constantly being evaluated. The variations encountered during the treatment are both geometric and dosimetric. They are represented by a reduction in the macroscopic tumors volume, a change in its position and a consequent dosimetric impact. The changes also concern organs at risk with a reduction of glandular structure volumes, and a different position which increases their doses. Delivered doses to noble structures (brainstem and spinal cord) may also increase. However, difficulties are encountered in its realization. There is a problem to perfectly reproduce the patient position during the second acquisition, which impacts the fusion quality between the two CT scans. This generates an imprecision in the definition of the same treatment isocentre on the second scanner. Also, there is a difficulty in accumulated doses calculation. The indication of adaptive radiotherapy remains a subject of controversy. It should be proposed for a subgroup of patients who could benefit from this new strategy. We present here an update on the state of the art of adaptive radiotherapy for nasopharyngeal cancer., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The aim of this work is to evaluate the anatomical changes of the glandular structures during the NPC IMRT and to study their dosimetric impacts., Patients and Methods: Twenty patients receiving IMRT for NPC were included. For each patient, a second dosimetric CT was performed at a dose of 38Gy, which was fused with the initial planning dosimetric CT. We calculated the volume percent change, the positional and dosimetric variation between the 2 scanners for the glandular structures (parotid, submaxillary, thyroid and pituitary)., Results: We observed a decrease in the volume of right and left parotids (-27.9% and -27.54%). It was correlated with the initial dose planned at its level. For the sub maxillary glands, the decrease was -36.1% on the right and -27.28% on the left. The value of reduction of the thyroid gland was -18.01%. A medial supra-millimeter migration of 2 and 1.15mm was found for right and left parotid glands respectively, correlated with GTV N reduction volume. We found a significant increase in mean doses for the parotid glands. It was 1.8±2.3Gy for the right and 1.5±2.7Gy for the left. For the right sub maxillary gland, the increase was about 0.35±2Gy and 3.79±5.2Gy for the thyroid., Conclusion: The modifications observed for glandular structures during NPC IMRT can explain the different toxicities caused by radiation. It seems also that a careful adaptation of the treatment plan should be considered during therapy., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: We report in this study, the dosimetric and carcinologic results of intensity-modulated technique for the reirradiation of nasopharyngeal carcinomas., Patients and Methods: Eight patients reirradiated with intensity-modulation technique between January 2015 and December 2017 were included. We noted for each patient: the minimum, maximum and average doses, the dose received by 95% (D95%), 98% (D98%) and 2% (D2%) of the volume to be irradiated, the homogeneity and conformity indices and doses to the organs at risk., Results: Target volume coverage was satisfactory with a median of D95% greater than 57Gy (95% of the prescribed dose). The median maximum dose received by the spinal cord and brainstem were 8.2Gy and 18.25Gy, respectively. After a median follow-up of 14.5 months [1-29 months], five patients were in complete remission of their disease. Overall survival at 2 years was 66.7%. An increase in preexisting late toxicity after the first irradiation (now grade 2 or above) was found in four patients (50% of cases)., Conclusion: Intensity-modulation is an attractive technique for reirradiation of the nasopharynx. It allows a better conformity of the dose to the target and a reduction of the doses on the already irradiated critical organs. This offers good control of the disease with fewer severe late toxicities., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: A retrospective study to evaluate the efficacy and safety of the addition of neoadjuvant chemotherapy to concurrent chemoradiotherapy in the treatment of nasopharyngeal carcinoma., Patients and Methods: Data from 62 patients treated for non-metastatic nasopharyngeal carcinoma were analyzed by comparing two groups of patients: a first group of 32 patients treated with 3 cycles of neoadjuvant chemotherapy based on docetaxel, cisplatin and 5-fluoro-uracil every 21 days followed by concurrent chemoradiotherapy (weekly cisplatin 40mg/m 2 with radiotherapy 70Gy, 2Gy per session, 5 sessions per week) and a second group of 30 patients treated with the same concurrent chemoradiotherapy., Results: After a median follow-up of 53.5 months, neoadjuvant chemotherapy showed a significant reduction in the rate of a distant metastatic relapses (3.3% vs. 10%, P=0.03). No significant difference in disease-free survival at 5 years (65.6% vs. 68.8%, P=0.46) or overall survival at 5 years (68.8% vs. 73.3%, P=0.46) was noted between the two groups. Induction chemotherapy was associated with febrile neutropenia of 15.6%. During concurrent chemoradiotherapy, hematological complications were greater in the first chemotherapy group (53% vs. 33%)., Conclusion: Induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil is a safe and effective option in the treatment of nasopharyngeal carcinoma. A better definition of high risk of relapse group would optimize the indications of this chemotherapy in the therapeutic arsenal., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: We represent in this study the long term results of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by concurrent chemoradiotherapy in Tunisian patients with locally advanced nasopharyngeal carcinoma. The objective of our study is to analyse the efficacy as well as the toxicity of this therapeutic protocol., Patients and Methods: Between January 2004 and December 2008, 32 patients with locoregional advanced non metastatic disease (T2b or above and/or N1 or above AJCC 2002) were treated in our institution by three cycles of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy every 21 days followed by concurrent chemoradiotherapy. Conventional radiotherapy was delivered using a cobalt 60 machine during 7 weeks with weekly cisplatin (40mg/m 2 )., Results: Twenty-nine patients (90%) had presented an objective clinical response in lymph nodes after neoadjuvant chemotherapy, with a complete response in 28%. Acute toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy was dominated by vomiting (59%), asthenia (40.6%), diarrhea (34.4%) and febrile neutropenia (15.6%). The complete response rate after the end of treatment was around 80%. The 5 years overall survival and disease-free survival were respectively 68.2% and 67.5%., Conclusion: Our results, in this field of study, are encouraging with acceptable toxicity despite the lack of intensity-modulated radiotherapy technique in our institution during the period of study., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: Concomitant chemotherapy (CT)-radiotherapy (RT) is a standard of care in locally advanced nasopharyngeal carcinoma (NPC) and a role for induction CT is not established., Methods: Patients with locally advanced NPC, WHO type 2 or 3, were randomized to induction TPF plus concomitant cisplatin-RT or concomitant cisplatin-RT alone. The TPF regimen consisted of three cycles of Docetaxel 75 mg/m2 day 1; cisplatin 75 mg/m2 day 1; 5FU 750 mg/m2/day days 1-5. RT consisted of 70 Gy in 7 weeks plus concomitant cisplatin 40 mg/m2 weekly., Results: A total of 83 patients were included in the study. Demographics and tumour characteristics were well balanced between both arms. Most of the patients (95%) in the TPF arm received three cycles of induction CT. The rate of grade 3-4 toxicity and the compliance (NCI-CTCAE v3) during cisplatin-RT were not different between both arms. With a median follow-up of 43.1 months, the 3-year PFS rate was 73.9% in the TPF arm versus 57.2% in the reference arm [hazard ratio (HR) = 0.44; 95% confidence interval (CI): 0.20-0.97, P = 0.042]. Similarly the 3 years overall survival rate was 86.3% in the TPF arm versus 68.9% in the reference arm (HR = 0.40; 95% CI: 0.15-1.04, P = 0.05)., Conclusion: In conclusion, several important aspects can be emphasized: the compliance to induction TPF was good and TPF did not compromise the tolerance of the concomitant RT-cisplatin phase. The improved PFS and overall survival rates needs to be confirmed by further trials.

Purpose: Retrospective analysis of clinical aspects and therapeutic results of nasopharynx cancer local failures., Patients and Methods: Forty patients with local failure with or without nodal involvement of nasopharyngeal carcinoma were treated between 1993 and 2013. Reirradiation of nasopharynx was delivered at the dose of 60Gy. Platinum-based chemotherapy was indicated in case of locally advanced disease and/or associated nodal failure., Results: The mean age at diagnosis of primitive tumour was 41.9 years (26-67 years). The mean time of relapse occurrence was 31.7 months (6-104 months). Sixty five percent of failures were confined to the nasopharynx. Nodal failure was seen in 14 cases. Twenty-eight patients had chemotherapy. Twenty-five patients had reirradiation of nasopharynx. Mean follow-up was 98 months (12-191 months). Fourteen patients were still alive and in complete remission. Five-year survival was 40.7%. Xerostomia was the most frequent late toxicity. No haemorrhage was seen., Conclusion: Reirradiation is the mainstay treatment of nasopharyngeal local failure. Late toxicity seems to decrease with novel techniques of reirradiation., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Aberrant expression of miR-10b has been described in many cancers but remains unexplored in nasopharyngeal carcinoma (NPC). Therefore, we aimed to study the miR-10b expression level in 43 NPC biopsies collected from Tunisian patients and three NPC xenografts. Then, we investigated the correlation between miR-10b expression and its upstream regulators LMP1/Twist1 as well as its adjacent gene HoxD4. We showed that miR-10b was significantly up-regulated in NPC biopsies compared to non-tumor nasopharyngeal tissues (fold change 153; p = 0.004) and associated with advanced clinical stage and young age at diagnosis (p = 0.005 and p = 0.011, respectively). In addition, over-expression of miR-10b was positively associated with the transcription factor Twist1 as well as the EBV oncoprotein LMP1 (fold change 6.32; p = 0.014, fold change 6.58; p = 0.01 respectively). Furthermore, higher level of miR-10b was observed in tumors with simultaneous expression of LMP1 and Twist1, compared to those expressing only Twist1 (fold change 2.49; p = 0.033). Meanwhile, the analysis of the link between miR-10b and its neighbor gene HoxD4 did not show any significant correlation (Fisher test p = 0.205; Mann-Whitney test p = 0.676). This study reports the first evidence of miR-10b over-expression in NPC patients. Furthermore, our findings can support hsa-miR-10b gene regulation through LMP1/Twist1 in NPC malignancy.

Neuroendocrine carcinoma of the head and neck is a rare entity. The parotid gland is the most commonly affected site. A nasopharyngeal site has not been previously described. We report a 35-year-old patient who consulted for tinnitus and nasal obstruction. The assessment found a nasopharyngeal tumour T4N0M0. The patient underwent 6 cycles of chemotherapy based on VP16 and cisplatin, followed by radiotherapy at a dose of 70 Gy to the nasopharynx and 50 Gy to the neck. The evolution was marked by clinical improvement and radiological stability. Six months after the end of treatment, the patient had a local and meningeal relapse. He received palliative care. He died 19 months after the end of treatment., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Cancer of the nasopharynx is an uncommon malignancy in France (incidence  =  0.5/year/100,000 men) but is endemic in areas like in South-East Asia. Exclusive radiation therapy used to be the standard and results in local control rates for T3-T4 tumors around 50-75 %. Intensity-modulated radiotherapy (IMRT) improves tumor coverage with a sparing of organs at risk and has to be privileged. Concurrent chemotherapy with IMRT achieved significant survival benefice with 5-year overall survival above 75 %. Concurrent radiochemotherapy with platinum is the most frequent scheme but induction and adjuvant chemotherapies are discussed to reduce distant failure: studies are currently ongoing. Follow-up aims to detect early local failures with a chance of cure and to manage long-term toxicities.

To further explore the epigenetic changes in nasopharyngeal carcinoma (NPC), methylation-sensitive arbitrarily primed PCR was performed on NPC biopsies and nontumor nasopharyngeal samples. We have shown mainly two DNA fragments that appeared to be differentially methylated in NPCs versus nontumors. The first, defined as hypermethylated, corresponds to a CpG island at the 5'-end of the tetratricopeptide repeat domain 40 (TTC40) gene, whereas the second, defined as hypo-methylated, is located on repetitive sequences at chromosomes 16p11.1 and 13.1. Thereafter, the epigenetic alteration on the 5'-TTC40 gene was confirmed by methylation-specific PCR, showing a significant aberrant methylation in NPCs, compared to nontumors. In addition, the bisulfite sequencing analysis has shown a very high density of methylated cytosines in C15, C17, and X666 NPC xenografts. To assess whether TTC40 gene is silenced by aberrant methylation, we examined the gene expression by reverse transcription-PCR. Our analysis showed that the mRNA expression was significantly lower in tumors than in nontumors, which is associated with 5'-TTC40 gene hypermethylation. In conclusion, we found that the 5'-TTC40 gene is frequently methylated and is associated with the loss of mRNA expression in NPCs. Hypermethylation of 5'-TTC40 gene might play a role in NPC development; nevertheless, other studies are needed.

Metastasis to the central nervous system, either through a hematogenous route or through the cerebrospinal fluid, is extremely rare in nasopharynx cancer. We aim to expose clinical aspects, therapeutic features and prognosis of nasopharyngeal carcinoma with brain metastases. We retrospectively reviewed the medical history of about 420 patients with nasopharyngeal carcinoma treated during 17 years at the university hospital of Sfax (Tunisia). Among them, three patients had brain metastasis. We excluded patients with direct extension to the brain. Tumours of the nasopharynx were locally advanced. The first patient had brain metastases at the initial diagnosis. The two other patients had brain metastases at 10 and 16 months during the follow-up. Ocular signs were the symptoms. Lesions were unique in two patients. Synchronous bone metastases were recorded in the three cases. All patients had whole brain radiation therapy and palliative chemotherapy. All patients had a progression of the disease and died. Brain metastases in nasopharynx cancer represent a rare event. Prognosis is poor, depending on age, surgical excision and synchronous metastases. Survival does not exceed 6 months., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To compare therapeutic results of nasopharyngeal carcinoma between adults and children., Patients and Methods: Three hundred and seventy seven patients with nasopharyngeal carcinoma received a radiotherapy between 1993 and 2007. Sixty-nine of them were 20years old or less. Two hundred and sixty eight patients received a chemotherapy (neoadjuvant or concomitant)., Results: Overall survival and disease-free survival at 5 years were 67 % and 59.4 % in all patients, respectively. Overall survival rates at 5 years in children and adults were 66 % and 64 %, respectively (P=0.17), disease-free survival rates at 5 years were 66 % and 57 %, respectively (P=0.17). Local failures occurred more frequently in adults than in children (1.4 % versus 14 %). However, metastatic events were frequently seen in children. Late toxicities were important in children, xerostomia was the most common one., Conclusion: Despite locally advanced disease in children, therapeutic results were better than in adults but not statistically significant. The use of treatment combination (chemotherapy and radiotherapy) in juvenile nasopharyngeal carcinoma may explain our findings., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Mediterranean area (MA) represents a zone of intermediate incidence (1-5/100,000) for NPC, the highest frequency being observed in North Africa (NA) where it is characterized by a bimodal age repartition due to a first adolescence peak. In MA and NA, NPC remain diagnosed at advanced stages which impact poorly on overall and disease-free survival. It's therapy in MA followed the progresses and standardisation of protocols, based on concomitant chemoradiotherapy (CCRT) alone or preceded by induction chemotherapy (ICT) in advanced (N2-3, T3-4) stages, while localized cases are managed irradiation alone. NPC overall an disease-free survival improved, due to the use of combined chemo and radiotherapy., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

A 30-year-old woman, with a history of nasopharyngeal carcinoma, which was treated by radiotherapy nine years previously, presented with occasional diplopia and recent headaches. A nasopharyngeal biopsy showed no recurrence. The imaging revealed a sphenoidal sinus mucocele. Endoscopic marsupialization of the mucocele allowed clinical improvement. A 56-year-old woman presented, five years after radiotherapy for nasopharyngeal carcinoma, with a fronto-orbital mass. CT-scan revealed a fronto-ethmoidal mucocele. Nasopharyngeal biopsy showed tumour recurrence. Marsupialization of mucocele was performed. Recurrence of the carcinoma was treated by radiotherapy and chemotherapy. Sphenoidal sinus mucocele developing after radiotherapy for nasopharyngeal carcinoma has rarely been reported. CT scan and MRI are useful tools in making the diagnosis. Biopsy is required to diagnose recurrence or associated radio-induced tumor. Endoscopic approach gives good results., (Copyright © 2011. Published by Elsevier SAS.)

Objectives: To analyze retrospectively the risk factors for occurrence of thyroid toxicity after radiotherapy for nasopharyngeal cancer and to demonstrate the necessity of a long-term post-therapeutic screening., Patients and Methods: Between 1993 and 2004, 239 patients with non-metastatic nasopharyngeal carcinoma were treated by conventional radiotherapy with or without chemotherapy. Radiotherapy was delivered by a standard fractionation (2 Gy/fraction, 5 fractions/week) for 157 patients and hyperfractionation (1.6 Gy/fraction, 2 fractions/day, 5 days/week) for 82 patients. An evaluation of thyroid late toxicity was performed according to tumor stage, age, gender, time after treatment, irradiation method and association or not with chemotherapy., Results: After a median follow up of 111 months, 72 patients (30%) had primitive and/or pituitary thyroid dysfunction. Fifty-seven patients (24%) experienced hypothyroidism, peripheral in 92% of cases (biological 73%, clinical 19%) and central in 8% of cases. Hypothyroidism was detected at a mean 37 months follow up. All patients received replacement treatment with l-thyroxin. The actuarial rate of hypothyroidism was 18.1%, 24.3% and 35% at respectively 3, 5 and 10 years. Only female gender was found as a risk factor for occurrence of hypothyroidism in univariate analysis. However, younger age and advanced tumor stage were associated with a higher risk but the difference was not significant (P = 0.08 for each). There was no difference for other factors: nodal stage, modality of radiation and chemotherapy treatment. The multivariate analysis did not show any risk factor., Conclusion: Thyroid dysfunction after radiotherapy for nasopharyngeal carcinoma is frequent and requires systematic screening to begin adequate treatment earlier. Only gender has been identified as risk factor in univariate analysis in this study., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Activation of the wingless-type (Wnt) signaling pathway is common in cancers. The Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist that acts by binding to Wnt ligands. We examined by methylation-specific PCR (MSP), whether WIF-1 is inactivated in 68 nasopharyngeal carcinomas (NPC), and 10 normal mucosa. We showed that the WIF-1 promoter was methylated in 89.7% of tumors, whereas all normal mucosa were unmethylated. The WIF-1 methylation was associated with the tumor, node, and metastasis (TNM) (p = .003) and the age (p = .014). The Wnt-5a mRNA was higher in tumors and correlated with TNM (p = .012). The methylation of WIF-1 contributes to the activation of the Wnt pathway in NPC.

In order to study the association of HLA-A, -B and/or DRB1, DQB1 and the nasopharyngeal carcinoma (NPC), 141 patients affected with NPC were typed for the HLA class I by serology method of microlymphocytotoxicity. Among these patients 101 were genotyped for HLA class II system by the PCR-SSP technique. HLA typing results were compared to those of 116 controls. We found that the HLA-A31 and -A33 antigens were significantly more expressed in patients than in the controls (P = 0.016 and 0.010, respectively) and the HLA-A19 antigen, was significantly more frequent in patients when compared to the controls (P = 0.007). The HLA-DRB1*03 and DRB1*13 alleles were significantly more frequent in patients as compared to the controls. The DRB1*01 allele was expressed with a frequency of 20.69% in the controls whereas it was only detected in 3.96% of the NPC patients. Furthermore, the DQB1*05 allele was expressed at a frequency which was significantly less important in affected patient (P = 0.03), whereas, the DQB1*02 allele was more frequent in patients (P = 0.643 x 10(-4)). Thus our study revealed a significant increase of HLA-A31, A33, A19, B16, B53 and DRB1*03, DRB1*13 and DQB1*02 alleles in our patients. These markers could play a predisposing role in the development of NPC. In contrast, a decrease of HLA-B14, -B35 and DRB1*01 and DQB1*05 alleles was found suggesting a likely protective effect.

Purpose: We retrospectively analyzed anatomoclinic, therapeutic and evolutive particularities of 74 young patients (< or =20 years) with nasopharyngeal carcinoma treated between 1993 and 2005., Patients and Methods: Initial work-up included a fiberoptic nasofibroscopy with biopsy, tomodensitometry and/or MRI of nasopharynx and neck, chest X-ray, abdominal ultrasonography and bone scan. Patients were treated with either primary chemotherapy (epirubicin and cisplatin) followed by radiotherapy or concomitant radiochemotherapy (five fluorouracil and cisplatin). Radiotherapy was delivered to a total dose of 70 to 75 Gy to nasopharynx and involved cervical lymph nodes and 50 Gy to the remainder cervical areas., Results: The median age was 16 years. Sixty-three percent of patients had undifferentiated tumors. Sixty-six percent had locally advanced tumor. With a median follow-up of 107 months, one patient presented a local relapse, 24 patients developed distant metastases with a median delay of 7 months. The 5 years overall survival and disease-free survival were 66 and 65 %. Late complications were dominated by dry mouth and endocrine disorders., Comments: Pediatric nasopharyngeal carcinoma is characterized by an early metastatic diffusion. Local control is excellent but with severe late toxicities. New techniques of radiotherapy and new molecules of chemotherapy could improve these results., (2010. Published by Elsevier SAS.)

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. Immunohistochemical 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 young patients. An improvement of the prognosis can be waited with concomitant chemotherapy and intensity modulated radiotherapy. However, randomized multi institutional studies are necessary to standardize the treatment of the NPC in childhood.

Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.

Purpose: A retrospective analysis of risk factors for late neurological toxicity after nasopharyngeal carcinoma radiotherapy., Patients and Methods: Between 1993 and 2004, 239 patients with non metastatic nasopharyngeal carcinoma were treated by radiotherapy associated or not to chemotherapy. Radiotherapy was delivered with two modalities: hyperfractionated for 82 patients and conventional fractionation for 157 patients. We evaluated the impact of tumour stage, age, gender, radiotherapy schedule and chemotherapy on neurological toxicity., Results: After a mean follow-up of 107 months (35-176 months), 21 patients (8.8%) developed neurological complications, such as temporal necrosis in nine cases, brain stem necrosis in five cases, optics nerve atrophy in two cases and myelitis in one case. Five- and ten-year free of toxicity survival was 95 and 84% respectively. Young patients had greater risk of temporal necrosis, and hyperfractionated radiotherapy was associated with a significantly higher risk of neurological complications (14.6% vs 5.7%, p=0.02). On multivariate analysis, hyperfractionation and age were insignificant., Conclusion: Late neurological toxicity after radiotherapy for nasopharyngeal carcinoma was rare. Younger age and hyperfractionation were considered as risk factors of neurological toxicity in our study.

PI3Ks (phosphatidylinositol 3-kinases) are lipid kinases that regulate signalling pathways involved in cell proliferation, motility, and adhesion. Somatic mutations and amplification of the PIK3CA gene have been reported in various types of human cancers. However, little is known about the frequency and prognosis role of PIK3CA activation in nasopharyngeal carcinoma (NPC). This study was conducted with the aim to screen for PIK3CA mutations in the two hot spot regions (exons 9 and 20) and to investigate for the PIK3CA gene amplification combined with the expression analysis of the phosphorylated Akt (pAkt). We showed that among 88 specimens, none had mutation in the helical domain (exon 9) and only one (1.13%) had mutation in the kinase domain (exon 20). On the other hand, PIK3CA gene amplification was found in 21.6% of cases and was strongly associated with distant metastasis (P = 0.002), lymph node involvement (P = 0.032), and advanced tumor stage (P < 0.001). Moreover, patients with PIK3CA copy number gain have a significant reduced overall survival time (P log rank = 0.02). We concluded that PIK3CA gene amplification is frequent in NPC and occurs in the advanced stage of NPC. Moreover, our finding emphasizes the association of PIK3CA gene amplification with worse prognosis in nasopharyngeal carcinoma.

Serological tests for Epstein-Barr virus (EBV) have been used for many years as diagnostic predictors of nasopharyngeal carcinoma. It has been shown previously that the conventional immunofluorescence assay has a limited diagnostic value, especially in young patients from North African area. In the search for more reliable immunoglobulin (Ig) G or IgA antibody markers for the diagnosis of nasopharyngeal carcinoma, immunoblot analysis was performed using a full spectrum of EBV proteins. Sera were collected from 108 patients with nasopharyngeal carcinoma and three control groups composed of 18 patients with lymphoma, 18 other patients with autoimmune diseases and 55 healthy EBV carriers. It was observed that the IgA Epstein-Barr nuclear antigen 1 (EBNA1), IgA early antigen (EA)-p138 and IgG EA-p138 antibodies represent the most specific anti-EBV responses in either young or older patients with nasopharyngeal carcinoma which yield higher positive rates compared to the three control groups. Since the IgA EBNA1 response showed the highest sensitivity value for the detection of nasopharyngeal carcinoma, a novel enzyme-linked immunosorbent assay (ELISA) was established using a GST-EBNA1 protein expressed in bacteria, containing the P-threonine EBNA1 subtype cloned from DNA EBV sequence of C15 xenograft cells. Detection rates were 85.7% and 94.9% in young and older patients with nasopharyngeal carcinoma respectively, while only 3.6%, 11.1%, and 16.6% in healthy EBV carriers, patients with lymphoma and patients with autoimmune diseases, respectively. Thus, IgA EBNA1 ELISA may be useful for early diagnosis and mass screening of nasopharyngeal carcinoma in Tunisia even in young patients., (2009 Wiley-Liss, Inc.)

Nasopharyngeal carcinoma affects preferentially young adults and is characterized by a high rate of node and visceral metastases that explains a part of therapeutic failure. We report a case of thyroid metastasis of a nasopharyngeal carcinoma. A 50-year-old patient had been treated of a nasopharyngeal carcinoma (T4 N2M0). Four years after a concomitant chemoradiotherapy, he presented with a compressive mass in the thyroid loge associated to cervical nodes. He underwent a total thyroidectomy and the definitive result concluded to an carcinome indifférencié de type nasopharyngé (UCNT) thyroid metastasis. A new concomitant chemoradiotherapy was delivered and consequently the tumor disappeared. Secondly, several node recurrences occurred. Metastasis of UCNT in thyroid gland is exceptional. Several problems are related to its aetiopathogenesis and to its treatment that is not systematized in the literature. The prognosis like for all metastatic forms of nasopharyngeal cancer is unfavorable.

Epigenetic modification is one of the mechanisms leading to gene silencing in neoplastic cells. By methylation-specific PCR, we analyzed the promoter methylation of three cancer-related genes: Ras Association domain Family 1A (RASSF1A), Death Associated Protein kinase (DAP-kinase) and Retinoic Acid Receptor beta2 (RARbeta2) in two NPC xenografts (C15 and C17), 68 primary NPC tumors, and nine normal nasopharyngeal epithelia. We showed that C15 and C17 displayed a complete promoter methylation of RASSF1A, RARbeta2 and DAP-kinase genes. In primary NPC tumors, the incidence of promoter methylation was very high for all three tested genes: 91% for RASSF1A, 88% for both RARbeta2 and DAP-kinase whereas all normal nasopharyngeal epithelia were unmethylated. Interestingly, our study revealed that aberrant promoter methylation of the three genes were statistically associated with the lymph node involvement (p < 0.0001). In addition, hypermethylation of RASSF1A was correlated with age at diagnosis (p = 0.047) and T stage (p = 0.037) while the RARbeta2 hypermethylation was associated with histological type (p = 0.011). Taken together, our results demonstrate that silencing of RASSF1A and RARbeta2 expression by promoter hypermethylation is associated with highly differentiated tumors, advanced tumor stage and the presence of lymph node metastasis. To assess the functional significance of the epigenetic silencing of RARbeta2 and DAP-kinase in NPC, we analysed the expression of two downstream target genes COX-2 and p53 by reverse PCR (RT-PCR) and immunohistochemistry (IHC). We revealed a significant association between expression of COX-2 and loss of RARbeta2 through aberrant methylation (p = 0.003) in NPC biopsies. We concluded that the inactivation of RASSF1A, RARbeta2 and DAP-Kinase by hypermethylation is a key step in NPC tumorigenesis and progression.

Cyclooxygenase 2 (COX-2) an inducible form of COX is frequently up-regulated in many human tumours. The expression of COX-2 in nasopharyngeal carcinoma (NPC) and its relationship to clinicopathological features were studied in Tunisian patients. COX-2 mRNA was detected in 91% of tumour tissues. Immunohistochemical analysis showed that COX-2 protein was strongly detected in tumour cells and the staining was mainly cytoplasmic. In contrast, COX-2 mRNA and protein were very low or undetectable in normal nasopharyngeal mucosa. Our result showed a significant association of COX-2 overexpression with the lymph node involvement, however, no correlation was observed with age, tumour stage, histological type and distant metastasis. Moreover, we showed that all tumour specimens co-overexpressed COX-2 and the EBV oncoprotein LMP1 corroborating the fact that LPM1 is known to induce COX-2. Altogether, our data suggests that the COX-2 is overexpressed in NPC biopsies and that is linked to the lymph node involvement.

Background: Aberrant methylation of tumor suppressor gene (TSG) promoters has been extensively investigated in nasopharyngeal carcinomas (NPC) from South East Asia but not from North Africa., Patients and Methods: The methylation status of p16, deleted in lung and esophageal cancer (DLEC1), zinc finger, MYND-type containing 10 (BLU) and E-cadherin gene promoters was investigated in 44 Tunisian NPC biopsies and three NPC xenografts, by methylation-specific PCR (MSP) combined with a quantitative assessment of some of the samples., Results: The frequencies of aberrant promoter methylation were similar to previous figures reported for Asian series: p16 27/44 (65%), DLEC1 38/44 (86.3%), BLU 15/44 (34.1%) and E-cadherin 35/44 (79.5%). Although in other malignancies, aberrant promoter hypermethylation increases with patient age, it was at the same high frequency in the juvenile and adult forms of Tunisian NPCs. However, there was a strong association between aberrant methylation of E-cadherin promoter and lymph node invasion (p < 0.01). In addition, aberrant methylation of the BLU promoter was significantly correlated with an undifferentiated histological type (p = 0.03)., Conclusion: Aberrant methylation of tumor suppressor genes occurs with the same high frequency in NPCs from North Africa as in South East Asia, regardless of patient age.

Background: The current retrospective study aimed to identify some determinants of survival in metastatic NPC., Methods: The study concerned 95 patients with metastatic nasopharyngeal carcinoma treated between 1993 and 2001. Statistical comparison between patients subgroups survival was carried out employing the log-Rank test (statistical significance was defined as p45 years and25 years), gender, performance status at diagnosis of metastatic disease (PS 0-1 or 2-3), time of metastasis diagnosis(at presentation or later), number of metastatic sites (single or multiple), specific metastatic sites(bone, liver, lung, distant nodes), number of bone metastasis (single or multiple), disease free survival (DFI) (6 months), prior chemotherapy, radiotherapy of metastatic sites., Results: Negative prognostic factors in univariate analysis were: poor PS (>or=1), multiple metastatic sites, multiple bone metastasis, previous chemotherapy, visceral or node metastasis and non irradiated metastasis. Poor PS, multiple metastatic sites, and prior chemotherapy were independently significant negative prognostic factors in multivariable analysis., Conclusions: In this study we identified new prognostic factors in univariate and multivariate analysis. A regular and careful follow-up of patients treated for NPC is then recommended in order to detect early metastatic dissemination (with minimal localizations) while patients have still a good PS.

A common polymorphism at codon 72 of TP53, the gene encoding the tumor suppressor protein p53, encodes either arginine or proline. These variants may be associated with tumor susceptibility since they interfere with the ability of TP53 to activate apoptosis, and might account for ethnic variation in cancer frequency. Using a polymerase chain reaction-restriction fragment length polymorphism assay, we tested peripheral blood samples from 115 patients with nasopharyngeal carcinoma (NPC) and from 83 healthy individuals. Patients with NPC (Arg/Arg = 38.26%, Arg/Pro = 41.73%, and Pro/Pro = 20%) showed a significantly different percentage of the Pro/Pro genotype, compared with the control population (Arg/Arg = 39%, Arg/Pro = 54%, and Pro/Pro = 7%) (P = 0.0307). No significant difference was observed between TP53 codon 72 polymorphism and age, sex, histological grade, and metastasis. These results provide evidence that individuals with the Pro/Pro genotype have an increased risk of developing NPC in Tunisia.

Epstein-Barr virus (EBV) is constantly present in undifferentiated and poorly-differentiated nasopharyngeal cancer. Thus, tumour-associated viral antigens are potential targets for immunotherapy. Recently, both preclinical and early clinical studies have shown that various strategies can enhance EBV-specific immunity. Moreover, significant anti-tumour effect has been observed, and was generally correlated with biological response. The present review discusses the rational for EBV-targeted immunotherapy and summarises the latest developments in this area.

Background and Purpose: Nasopharyngeal carcinoma (NPC) is generally responsive to radiation therapy. However therapeutic results after conventional radiotherapy remain relatively poor especially for patients with locoregional advanced NPC. The aim of this study was to evaluate the impact of a split course bifractionated radiotherapy regimen in a phase III randomised trial., Patients and Methods: From January 1997 to September 2003, 154 patients with M0 histologically proven NPC were treated in our institution. They were staged according to the American Joint Committee on Cancer - International Union Against Cancer (AJCC-UICC) 1986 TNM classification. Patients with locally advanced nodal disease (N2-N3) received induction chemotherapy. All patients were randomised to receive either conventional radiotherapy at 2 Gy/fraction/day, 5 days/week to 70 Gy/7 weeks or split course bifractionated radiotherapy at 1.6 Gy/fraction, twice daily, 5 days/week to 70.4 Gy/6 weeks. Response and toxicity were evaluated according to the WHO and RTOG criteria., Results: Patients were well balanced between the two arms. The complete remission rate was 91% in conventional radiotherapy arm and 93% in bifractionated radiotherapy arm (p=0.3). There was more grade II-III skin fibrosis in experimental arm with a 5 year actuarial probability of 66% vs 52% (p=0.04). Locoregional and distant relapses occurred in 34% of cases in conventional arm and 38% in experimental arm (p=0.28). With a median follow-up of 56 months, the 5 year overall survival and the disease free survival rates were, respectively (71% and 61%), in conventional arm and (62% and 60%) in bifractionated arm, the difference being statistically non significant., Comments: The present trial comparing conventional radiotherapy to a split course bifractionated radiation therapy failed to demonstrate significant improvement in locoregional control and survival in experimental arm which was associated with more grade II-III skin fibrosis.

Purpose: To determine the level and prognostic significance of c-kit expression in the two age groups of North African nasopharyngeal carcinomas., Patients and Methods: A retrospective study of 99 NPC specimens from Tunisian patients was investigated by immunohistochemistry. Immunohistochemical data were correlated with Epstein-Barr virus LMP1 expression and pathological, clinical and survival parameters., Results: c-kit was detected in 79% of the cases for patients under 30 years of age (juvenile form) but in only 56% of specimens in patients over 30 years (P=0.039) and was significantly over-expressed for patients with lymph node involvement (P=0.015). LMP1 score was 5.78 (+/-1.84) for c-kit negative tumors compared to 8,23 (+/-2.39) for c-kit positive tumors (P=0.002). Multivariate analysis including age, lymph nodes involvement and LMP1 expression as co-variables, showed that only age (P=0.027) and LMP1 expression (P=0.005) were significantly correlated to the c-kit expression., Conclusion: c-kit is highly expressed in the juvenile form of North African nasopharyngeal carcinomas. There is a significant association between LMP1 and c-kit expression. The contrasted levels of C-kit expression in the two age groups strengthen the hypothesis that these clinical forms result from distinct oncogenic mechanisms.

Many studies suggest that the focal distribution of nasopharyngeal carcinoma (NPC) may be influenced not only by host genetics, diet and environments but also by interplay with Epstein-Barr virus (EBV) genetics. Specific EBV gene variants (the A and C types, the BamHI f configuration, a C terminal 30 bp deletion and a N terminal loss of an XhoI site in the BNLF1 gene) have been explored in high incidence areas in southern Asian NPC patients. In contrast, in Tunisia where NPC represents the most frequent type of Head and Neck cancer the distribution of these polymorphisms remains poorly investigated. In order to characterize the epidemiology of EBV variants in Tunisian NPC patients, we have investigated the A or B type of the EBV nuclear antigen (EBNA)2 gene, the C or D type of the BamHI W1/I1 region, the F/f variants of the BamHI F region and the presence or the absence of the XhoI site, 30 bp deletion and Taq1 site in the BNLF1 gene in 47 NPC biopsies, 12 being younger than 30 and 35 older than 30. Our results show a unique genetic profile of the tumor EBV strains regarding the A and D types, the prototype F and retention of the XhoI restriction site in the N terminal region of BNLF1 gene. With regard to the C terminal region of this gene, four genetic profiles were detected: (1) the occurrence of the 30 bp deletion in association with the Taq1 site in 39 cases (83%), (2) the presence of the Taq1 site by itself in 5 cases, (3) the occurrence of the 30 bp deletion by itself in 2 cases and (4) the occurrence of a new deletion of 81 bp covering the 30 bp deletion in association with the Taq1 site in one case. With the exception of the 81 bp deletion, which has not been previously described in the literature, the summarized results have shown the same genetic profile in Tunisian NPC tumor isolates as tumor isolates from other North African and Mediterranean countries. Hence, the observed EBV polymorphisms are not fully specific of to the Tunisian NPCs. Nevertheless, the notion of a divergence between North African and Asian tumor EBV isolates is reinforced by this study.

Purpose: The objective of this retrospective study was to discuss the epidemioclinical criteria and the therapeutic results of metastatic nasopharyngeal carcinoma., Patients and Methods: The current study concerned 95 patients with histologically proven nasopharyngeal carcinoma who were metastatic at diagnosis or who had developed late metastasis. We reviewed the epidemioclinical records of all the patients. Patients were treated with chemotherapy (BEC regimen: bleomycin, epirubicin and cisplatin or PBF regimen: bleomycin, 5-fluorouacil and cisplatin) and radiotherapy of pauci metastatic localizations (single or double) or bone metastasis with high risk of compression or fracture+/-associated with locoregional radiotherapy for patients who were metastatic at diagnosis. Response was assessed according to the WHO criteria. Overall survival was calculated according to the Kaplan-Meier method. A long-term disease-free survival was defined from 36 months., Results: There were 34 patients who were metastatic at diagnosis and 61 patients who had developed late metastasis. The mean age was 41.5 years (sex-ratio: 3.1). Bone metastases were the most frequent (83%). Objective and complete response rates were respectively 75% and 70%, and 32% and 16% for BEC and PBF regimens. Twenty-five patients received radiotherapy for pauci metastatic localizations, among whom 19 patients who were metastatic at diagnosis received locoregional irradiation. The overall survival probability was of 15% for three years. Eleven patients were long survivors (extremes: 36 and 134 months)., Conclusion: Therapeutic results were comparable to those reported in other series using platin combination chemotherapy. Radiotherapy of metastasis yielded to long-term survival.

Nasopharyngeal carcinoma (NPC) occurs with a striking geographic distribution, it is endemic in certain areas of Southeast Asia and North Africa. NPC is tightly linked to Epstein-Barr virus (EBV), however, only a small subset of EBV genes are expressed, among them the latent membrane protein 1 (LMP1). LMP1 is considered as the main EBV oncoprotein and its 30 bp deleted-variant has been reported to be more prevalent in biopsies of NPC. We have assessed the 30 bp deletion and the XhoI polymorphisms of the BNLF1 gene in 30 peripheral bloods of NPC patients and 62 nasopharyngeal biopsies, 42 being confirmed as undifferentiated nasopharyngeal carcinoma and 20 are normal nasopharyngeal epithelium cells. Our results show that 100% of individuals retained the XhoI restriction site. A rare NPC variant, having a 69 bp deletion in the C-terminus region of the BNLF1 gene, covering the 30 bp deletion, was found in two NPC biopsies. The deleted 30 and 69 bp deleted-variants are significantly (p = 0.006) more frequent in NPC (71.42%) than in control biopsies (52%). In peripheral blood of NPC patients, the deleted-variants (47%) are also lower than in tumor tissues (p = 0.0004), suggesting that the deletion could be associated with a risk of tumor genesis. Direct repeats, located at the extremities of the 30 and 69 bp deletions, should be involved in this process. We propose that other deletions could be found since another similar direct repeat is present at the vicinity of the former ones.

Purpose: The aim of this work is to study the epidemiological, clinical and evolutive characteristics of the erysipela in patients treated for nasopharyngeal carcinoma (NPC)., Patients and Methods: Between January 1993 and June 2003, 212 patients were treated for NPC in the radiotherapy department of Sfax hospital. Twenty-two patients among them have presented an erysipela. A neoadjuvant chemotherapy was used for 16 patients with N2-N3 disease. Locoregional radiotherapy was delivered for all of patients., Results: The mean age was 35 years (range: 10 and 69), sex-ratio was 1.2. The median delay between the appearance of erysipela and the end of the treatment was 16 months. The main localisation was the face. The main clinical manifestations were fever in 86% of cases and erythema in 77% of cases. Immediate evolution was favorable in all cases after antibiotherapy. Recurrences were observed in 45% in cases., Conclusion: Erysipela is a common skin infection readly found in patients with venous insufficiency. In our study we found a significant correlation between the frequency of erysipela and dystrophic complications. The incidence of erysipela in the face and cervical region after radiotherapy is unknown.

Purpose: 1/ To evaluate the incidence of hypothyroidism following radiotherapy in the management of breast and nasopharyngeal carcinomas, 2/ to define the role of a systematic post therapeutic screening., Patients and Methods: From January 1996 through March 2001 a systematic evaluation of the clinical and the biological thyroid function was performed on a cohort of 84 patients that received supraclavicular irradiation. Selected patients had either a mammary (37 cases) or a nasopharyngeal (47 cases) carcinoma. Initial work up included thyroid inspection and palpation, and biological tests: serum FT4 and TSH levels, radioimmunochemistry, completed by dynamic thyroid stimulation, using TRH, in case of border line low T4 or isolated high TSH levels. Tests were repeated every three months the first year, and then every six months. Replacement therapy with L Thyroxin was administered in case of hypothyroidism., Results: All selected patients had a normal function initially. With a mean two years follow up (1-5 years), 24 patients (29%) experienced hypothyroidism, half of whom (13 cases) being purely biological. Five patients (11%), with a nasopharyngeal carcinoma, presented also with associated pituitary failure. Clinical symptoms were minor or mild in all cases. Hypothyroidism was detected at a mean 21 months follow up. In 2 patients, hypothyroidism disappeared spontaneously within 6 months. Possible predictive factors were evaluated: age of the time of radiation, gender, percentage of irradiated thyroid, total dose, dose per fraction, tumour type and chemotherapy. Only age appeared significantly correlated with thyroid dysfunction (range: 10-30 years, P=0.002)., Conclusion: Hypothyroidism is a frequent and certainly underestimated complication following radiotherapy of the neck. In such patients, a systematic clinical and biological evaluation every three months the first year, and then every six months until five years is recommended.

Background: Undifferentiated nasopharyngeal carcinomas are rare in a majority of countries but they occur at a high incidence in South China and to a lesser extent in North Africa. They are constantly associated with the Epstein-Barr virus (EBV) regardless of patient geographic origin. In North Africa, the distribution of NPC cases according to patient age is bi-modal with a large group of patients being around 50 years old (80%) and a smaller group below 25 years old. We and others have previously shown that the juvenile form of NPC has distinct biological characteristics including a low amount of p53 and Bcl2 in the tumor tissue and a low level of anti-EBV IgG and IgA in the peripheral blood., Results: To get more insight on potential oncogenic mechanisms specific of these two forms, LMP1 abundance was assessed in 82 NPC patients of both groups, using immuno-histochemistry and semi-quantitative evaluation of tissue staining. Serum levels of anti-EBV antibodies were simultaneously assessed. For LMP1 staining, we used the S12 antibody which has proven to be more sensitive than the common anti-LMP1 CS1-4 for analysis of tissue sections. In all NPC biopsies, at least a small fraction of cells was positively stained by S12. LMP1 abundance was strongly correlated to patient age, with higher amounts of the viral protein detected in specimens of the juvenile form. In contrast, LMP1 abundance was not correlated to the presence of lymph node or visceral metastases, nor to the risk of metastatic recurrence. It was also independent of the level of circulating anti-EBV antibodies., Conclusion: The high amount of LMP1 recorded in tumors from young patients confirms that the juvenile form of NPC has specific features regarding not only cellular but also viral gene expression.

Nasopharyngeal carcinoma (NPC) in Tunisia is characterized by its bimodal age distribution involving juvenile patients of 10-24 years and adult patients of 40-60 years. Three serological techniques were compared for primary diagnosis (N = 117) and post-treatment monitoring (N = 21) of NPC patients separated in two age groups. Immunofluorescence assay (IFA) was used as the "gold standard" for detection of IgG and IgA antibodies reactive with Epstein-Barr virus (EBV) early (EA) and viral capsid (VCA) antigens. Results were compared with ELISA measuring IgG and IgA antibody reactivity to defined EBNA1, EA, and VCA antigens. Immunoblot was used to reveal the molecular diversity underlying the anti-EBV IgG and IgA antibody responses. The results indicate that young NPC patients have significantly more restricted anti-EBV IgG and IgA antibody responses with aberrant IgG VCA/EA levels in 78% compared to 91.7% in elder patients. IgA VCA/EA was detected in 50% of young patients versus 89.4% for the elder group (P < 0.001). Immunoblot revealed a reduced overall diversity of EBV antigen recognition for both IgG and IgA in young patients. A good concordance was observed between ELISA and IFA for primary NPC diagnosis with 81-91% overall agreement. Even better agreement (95-100%) was found for antibody changes during follow-up monitoring, showing declining reactivity in patients in remission and increasing reactivity in patients with persistent disease or relapse. ELISA for IgA anti-VCA-p18 and immunoblot proved most sensitive for predicting tumor relapse. VCA-p18 IgA ELISA seems suitable for routine diagnosis and early detection of NPC complication., ((c) 2005 Wiley-Liss, Inc.)

Objective: To collect second cancers occurring in the head and neck area after treatment by chemotherapy and/or radiotherapy for undifferentiated nasopharyngeal carcinoma in Tunisia., Patients and Methods: This is a retrospective study of patients developing second cancers after treatment for nasopharyngeal UCNT by radiotherapy and/or chemotherapy. To be retained in this study, second tumour had to be histologically different from the initial UCNT, localised in the irradiated area and occurring after a minimal delay of 3 years., Results: We collect 11 cases of second cancers occurring among 2346 patients treated from 1984 to 2001 in Tunisia (0.46%). Patients have been treated for nasopharyngeal UCNT mainly advanced T3-T4 (72%) or N2-N3 (63%). Median age was 20 years (11 to 48) with a sex-ratio of 0.3 (3 M/8 F). Treatment protocol included primary chemotherapy in 4 cases (adriamycin-cisplatin) or adjuvant (in 4) associated to the loco-regional irradiation at a mean dose of 72 Gy (70 to 75). Median delay of second cancer occurrence was 9 years (3 to 17). Tumors were epidermoid carcinomas in 4 cases, fibrosarcomas (2), osteosarcomas (2), glioblastoma (1) and basocellular carcinomas in 2. Second tumors have been treated by surgery alone in 4 cases and chemotherapy alone in 7 patients. No patient have been reirradiated. Median survival was 17 months, 4 patients died and 7 are still alive including 4 in complete remission (24+, 36, 36 and 48+ months) and 3 with progressing disease (8, 16 and 18 months)., Conclusion: Even very rare, second cancers after treatment for UCNT need to be detected and have a poor prognosis.

Standard therapy for nasopharyngeal carcinoma (NPC) in children has generally followed the guidelines established for adults. We report here, the treatment outcomes in 32 children and adolescents with NPC and we discuss treatment approaches. Between 1993 and 1997, 32 NPC patients aged

Aims: The thyroid dysfunction after radiotherapy has led to evaluate the dose received by thyroid during nasopharynx and breast carcinoma irradiation. This evaluation was facilitated by in vivo dosimetry. The aims of this work were to evaluate the thyroid dose and to compare released dose at the reference point in the two localizations., Patients and Methods: A total of 30 patients were evaluated: 18 patients with nasopharynx carcinoma and 12 patients with breast carcinoma were included in the final analysis. In the first group, the total thyroid but the isthmus was irradiated. On the other hand, in the second group, only one thyroid lobe was included into the target volume. All patients have been treated by gamma rays of cobalt 60 and the thyroid absorbed dose was measured by semiconductor dosimeters (Scanditronix DPD6). These dosimeters were calibrated in the same geometric conditions of the irradiation., Results: The measured absorbed dose of the thyroid parenchyma was equal to the calculated absorbed dose at the target that has been specified at a depth of -3 cm. Under the block, the isthmus received 5.1 +/- 0.9 Gy (9.9 +/- 1.8%) in nasopharynx carcinoma irradiation. However, in breast carcinoma irradiation, the distal thyroid lobe and the isthmus received 2.9 +/- 0.7 Gy (6.55 +/- 1.56%) and 3.69 +/- 0.77 (8.39 +/- 1.76%), respectively., Conclusions: This study shows that the thyroid received a dose equal to the prescribed dose in both nasopharynx and breast cancer patients. It is recommended to follow the function of the thyroid gland in these patients.

Nasopharyngeal carcinomas (NPCs) are consistently associated with the Epstein-Barr virus (EBV). As Bcl-2 and Bcl-X are co-expressed in EBV-transformed B-lymphocytes, we attempted to determine their status in malignant NPC cells. A retrospective series of 100 NPC specimens from untreated Tunisian patients was investigated by immuno-histochemistry. Twenty seven of the patients were below 30 years old and therefore classified in the "juvenile" form of north African NPCs. Bcl-2 and Bcl-X expression was assessed semi-quantitatively using a score based on the percentage of positive cells and staining intensity. Intense Bcl-X expression was detected in malignant cells of 100% biopsy samples with similar scores for patients below 30 years or those aged 30 or over. Bcl-2 was detected in 89% biopsies but its expression differed considerably between the samples. The average Bcl-2 score was much lower for patients under 30 years (4.4+/-1.5 compared to 6.5+/-2 for older patients; P<10(-6)). Multivariate analysis demonstrated that no other clinical parameter, except the primary tumor size, was correlated to the Bcl-2 score. Bcl-X and Bcl-2 are co-expressed in 89% of NPCs whereas their expression is mutually exclusive in other head and neck carcinomas (particularly squamous cell carcinomas, SCC). The constantly high expression of Bcl-X is consistent with it being induced by the EBV protein Epstein-Barr nuclear antigen 1 (EBNA1), as recently reported in a murine model. The contrasted levels of Bcl-2 expression in the two age groups strengthen the hypothesis that these clinical forms result from distinct oncogenic mechanisms.