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BACKGROUND: Previous studies have shown that poor prognostic indicators of inflammatory breast cancer (IBC) include younger age at diagnosis, poorer tumor grade, negative estrogen receptor, lesser degree of pathological response in the breast and lymph nodes. METHODS: This is a retrospective study conducted over a period of 12 years between January 2008 and December 2019 at the medical oncology department at Habib Bourguiba University Hospital in Sfax. We included in this study women with confirmed IBC. We excluded patients with no histological evidence, those whose medical records were unusable. Data collection was done from patient files. The aim of this study was to analyze the factors of poor prognosis of this entity. RESULTS: During a period of 12 years (2008–2019), 2879 cases of breast cancer were treated at Habib Bourguiba hospital in Sfax. 81 IBC were included. The incidence of IBC was 3%. The average age was 52.4 years (26–87 years). Invasive ductal carcinoma was the most frequent histological type (85.7%). Hormone receptor were positive in 64%. Human Epidermal Growth Factor Receptor-2 (HER2) was overexpressed in 35.9% of cases. The proliferation index Ki-67 was analyzed in 34 cases. It was >20% in 24 cases. Luminal A, luminal B, HER2+++, triple negative were found in 13%, 50.7%, 16% and 20% respectively. Metastases at diagnosis were found in 38%. Poor prognostic factors significantly influencing overall survival in univariate analysis were metastatic stage, high SBR grade, lymph node involvement, in particular greater than 3 nodes, negative hormone receptors, triple-negative molecular profile and occurrence of relapse. CONCLUSION: Number of positive lymph nodes greater than 3 and the occurrence of relapse were independent prognostic factors in case of localized IBC. Metastatic stage was associated with a very poor prognosis.

Resume Le recepteur HER2 (Human Epidermal Growth Receptor 2) est un recepteur transmembranaire a activite tyrosine kinase qui est surexprime dans 25 a 30 % des carcinomes mammaires. Son activation est associee a une exageration de la proliferation cellulaire avec une augmentation de la capacite de reparation entrainant une radioresistance accrue. Sur les tissus sains, essentiellement cardiaques, l’activation des recepteurs joue un role cardioprotecteur. Le Trastuzumab, premier anti-HER2 utilise pour traiter les patientes atteintes de cancers du sein avec surexpression des recepteurs HER2, inhibe la cascade de reaction aboutissant a la proliferation des cellules tumorales permettant ainsi de restaurer la radiosensibilite cellulaire. Cependant, l’association du Trastuzumab a la radiotherapie supprime l’effet cardioprotecteur des recepteurs HER2 sur les cellules myocardiques ce qui majore le risque de cardiotoxicite. C’est ainsi que l’association concomitante de ces deux modalites therapeutiques a longtemps ete un sujet de controverse. Les progres realises aussi bien sur le plan technique de radiotherapie que pour les moyens de detection precoce des lesions cardiaques, pourraient limiter la cardiotoxicite de cette association. Nous proposons a travers cette mise au point, une revue de la litterature sur les bases biologiques et le benefice-risque de l’association concomitante de radiotherapie et Trastuzumab dans le traitement adjuvant des cancers du sein non metastatique HER2 surexprime et nous discutons les modalites de son optimisation.

Resume Objectif de l’etude Rapporter les particularites epidemiocliniques, therapeutiques et evolutives des carcinomes canalaires de la parotide. Materiel et methodes Etude retrospective portant sur cinq cas de carcinome canalaire de la parotide primitive ou secondaire, pris en charge a notre service de 2007 a 2019. Resultats Il s’agissait de quatre hommes et une femme d’âge moyen de 61,4 ans. Une patiente avait ete traitee pour un carcinome canalaire infiltrant mammaire. Le motif de consultation etait une tumefaction parotidienne dans quatre cas et une asymetrie faciale dans un cas. Une permeation cutanee a ete trouvee dans un cas. Quatre patients ont eu une parotidectomie totale avec sacrifice du nerf facial dans trois cas et etendue a la peau dans un cas. Un evidement ganglionnaire a ete realise dans quatre cas. Une patiente a eu une biopsie parotidienne diagnostique. Le carcinome canalaire etait primitif dans quatre cas et metastatique d’un cancer mammaire dans un cas. Une radiotherapie postoperatoire a ete realisee pour les quatre patients operes. Le controle local et a distance a ete obtenu dans trois cas. Une recidive locale et meningee a ete observee dans un cas. Pour la patiente ayant un carcinome mammaire, elle avait une progression polymetastatique pulmonaire, osseuse, hepatique et cerebrale. Conclusion Le carcinome canalaire est une forme rare et agressive des cancers parotidiens de haut grade. Il peut etre primitif ou secondaire. Le traitement se base sur la chirurgie et la radiotherapie. Le pronostic est reserve.

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 14years (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. Resumo Introdução: O carcinoma nasofaríngeo tem o maior potencial metastático de todos os tipos de câncer de cabeça e pescoço. O tempo de sobrevida dos pacientes com carcinoma nasofaríngeo melhorou significativamente nas últimas décadas devido ao uso combinado de quimioterapia e radioterapia e os avanços nas técnicas de radioterapia. No entanto, aproximadamente 30% dos pacientes com carcinoma nasofaríngeo têm um prognóstico ruim, principalmente devido a metástases a distância. Objetivo: Identificar a sobrevida e os fatores prognósticos no carcinoma nasofaríngeo metastático. Método: Foi feita uma análise retrospectiva de pacientes tratados por carcinoma nasofaríngeo metastático sincrônico ou carcinoma nasofaríngeo metastático metacrônico por 14 anos (2003-2016). A sobrevida global foi analisada pelo método de Kaplan-Meier e comparada pelo teste de log-rank para toda a população e ambos os grupos de pacientes. A análise multivariada foi feita com o modelo de Cox; valores de p < 0,05 foram considerados como significância estatística. Resultados: Foram incluídos 112 pacientes com carcinoma nasofaríngeo metastático (51 com carcinoma nasofaríngeo metastático sincrônico e 61 com carcinoma nasofaríngeo metastático metacrônico). Em toda a população, a mediana da sobrevida global foi de 10 meses (1–156 meses). Na análise multivariada, sexo feminino, baixo status de desempenho (OMS > 1) e metástase metacrônica foram fatores prognósticos independentes. Nos pacientes com carcinoma nasofaríngeo metastático sincrônico, a mediana da sobrevida global foi de 13 meses (1–156 meses). Na análise multivariada, os fatores prognósticos independentes foram doença não oli-gometastática, toxicidade grave à quimioterapia (G3 – G4) e falta de irradiação nasofaríngea e do sítio metastático. Nos pacientes com carcinoma nasofaríngeo metastático metacrônico, a mediana da sobrevida global foi de 7 meses (1–41 meses). Na análise multivariada, o baixo status de desempenho (OMS > 1) foi um fator prognóstico independente. Conclusão: Pacientes oligometastáticos com carcinoma nasofaríngeo metastático sincrônico tiveram melhor sobrevida. O tratamento locorregional do carcinoma nasofaríngeo primário melhorou a sobrevida em pacientes com carcinoma nasofaríngeo metastático sincrônico que responderam à quimioterapia de indução. A irradiação local dos locais metastáticos melhorou a sobrevida dos pacientes com carcinoma nasofaríngeo metastático. A toxicidade de quimioterapia de grau 3 ou 4 alterou a sobrevida entre pacientes com carcinoma nasofaríngeo metastático sincrônico.

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.

Resume Objectif de l’etude L’objectif de ce travail etait d’evaluer les changements anatomiques des structures glandulaires survenus au cours de l’irradiation des carcinomes nasopharynges et d’etudier leurs impacts dosimetriques. Patients et methodes Vingt patients en cours de radiotherapie pour un carcinome nasopharynge non metastatique ont ete inclus dans cette etude. Apres la planification dosimetrique initiale, une deuxieme scanographie a ete faite a 38 Gy dans les memes conditions. Il a ete releve les changements volumetriques, positionnels ainsi que dosimetriques, entre les deux scanographies pour les structures glandulaires (parotides, glandes sous-maxillaires, thyroide et hypophyse). Resultats Une diminution moyenne du volume des parotides droites et gauches a ete observee (respectivement − 27,9 % et − 27,5 %). Pour les glandes sous-maxillaires, la diminution etait de − 36,1 % a droite et − 27,2 % a gauches. Elle etait de − 18,01 % pour la glande thyroide. Une migration supra-millimetrique dans le sens medial de 2 et 1,15 mm a ete trouvee pour l’isocentre des glandes parotides droite et gauche respectivement. Elle etait correlee avec la reduction du volume tumoral macroscopique ganglionnaire (GTVN) (r = 0,45 et 0,5). Une augmentation statistiquement significative des doses moyennes a ete documentee au niveau des glandes parotides de 1,8 ± 2,3 Gy a droite et de 1,5 ± 2,7 Gy a gauche, de la glande sous-maxillaire droite de 0,35 ± 2 Gy et de la thyroide de 3,79 ± 5,2 Gy. Conclusion Les modifications anatomiques et dosimetriques expliquent en partie les toxicites causees par le rayonnement sur les structures glandulaires et constituent une piste pour l’implementation d’une nouvelle strategie therapeutique qui est la radiotherapie adaptative.

BackgroundThe incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum ofBRCAmutations remains little explored in Tunisian patients in particular in the southern region.MethodsWe sequenced the entire coding regions ofBRCA1andBRCA2genes using next generation sequencing (NGS) in 134 selected patients with BC and/or OC.ResultsAmong the 134 patients, 19 (14.17%) carried pathogenic mutations (10 areBRCA1mutation carriers and 9 areBRCA2mutation carriers) that are mainly frameshift index (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA inBRCA2and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 inBRCA1and 2 inBRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A > T, (K3326*) inBRCA2exon 27.BRCAcarriers correlated significantly with tumor site (p = 0.029) and TNBC cases (p = 0.008). In the groups of patients aged between 31 and 40, and 41–50 years,BRCA1mutations occurred more frequently in patients with OC than those with BC, and converselyBRCA2carriers are mostly affected with BC (p = 0.001, and p = 0.044 respectively).ConclusionsThe overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast/ovarian cancer. We identified recurrent mutations as the c.1310_1313 delAAGA inBRCA2gene and the c.5030_5033 delCTAA inBRCA1gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of BC and/or OC.

AIM The objective of this study is to report the therapeutic results of the preservation strategy in locally advanced laryngeal cancers. PATIENTS AND METHODS Between January 2008 and December 2015, 24 patients with locoregional advanced non-metastatic laryngeal cancer (T2-4/N0-2) were collected retrospectively. Different therapeutic sequences were used: either induction chemotherapy followed by concurrent chemoradiotherapy or induction chemotherapy followed by radiotherapy or concurrent chemoradiotherapy or radiotherapy alone. RESULTS The objective response rate was 85.7%. Overall survival rates at 1 year, 3 years and 5 years were 91.3%, 80.2% and 53.5%, respectively. Administration of induction chemotherapy did not improve overall survival. The 1-year overall survival was 83.3% in the induction chemotherapy group vs 94.1% for those who did not received induction chemotherapy (p = 0.7). CONCLUSION Our study showed the feasibility of this preservation strategy in clinical practice, with acceptable term toxicity.

Background Trastuzumab improves therapeutic outcomes among patients with human epidermal growth factor receptor 2-positive breast cancer (BC). However, it is associated with a risk of treatment-induced cardiotoxicity. The aims of this study were to determine the frequency of trastuzumab-induced cardiotoxicity (TIC) in Tunisian patients, to study the effects of trastuzumab on cardiac biomarkers and echocardiographic parameters using the speckle tracking technique and to identify risk factors of occurrence of TIC. Patients and methods Fifty women with newly diagnosed human epidermal growth factor receptor 2-positive BC treated with or without anthracycline followed by taxane and trastuzumab were enrolled, from November 2016 to December 2018, to be evaluated every 3 months during trastuzumab treatment (total of 15 mo) using echocardiograms and blood samples. Left ventricular ejection fraction (LVEF) and peak systolic left ventricular longitudinal myocardial strain were calculated. Ultrasensitive troponin I (TNI) and N-terminal pro-B-type natriuretic peptide (NT pro-BNP) were also measured. Results LVEF decreased from 62±3.12% to 59±3.3% (P=0.005) over 15 months. Seven patients (14%) developed cardiotoxicity, as defined by the European Society of Cardiology; of these patients, 2 (4%) had symptoms of heart failure. Hypertension, left ventricular longitudinal myocardial strain, Log TNI, and NT pro-BNP measured at the completion of anthracyclines were significantly correlated to TIC occurrence. At multivariate analysis, the degree of LVEF decline was the only independent factor correlated to TIC (hazard ratio=2.4; 95% confidence interval=1.2-6.03; P=0.049). This TIC was reversible in 86% of cases. Conclusion In patients with BC treated with trastuzumab, in addition to the evaluation of the LVEF, systolic longitudinal strain, TNI, and NT pro-BNP measured at the completion of anthracyclines are useful in the prediction of subsequent TIC.

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).

Background: To evaluate the patterns of failure in patients treated for head and neck carcinoma of unknown primary and to discuss treatment practices concerning radiotherapy target volumes definition and dose prescription. Methods: Eleven patients presenting a locoregional recurrence after head and neck carcinoma of unknown primary treatment with curative-intent radiochemotherapy performed between 2007 and 2017 in the departments of radiation oncology of 2 French cancer institutes. Images of the computed tomography scan or the magnetic resonance imaging performed at the time of the recurrence were fused with those of the simulation computed tomography scan to delimit a volume corresponding to the recurrence and to define the area of relapse compared to the volumes treated. Results: Irradiation was unilateral in 6 cases and bilateral in 5 cases. The median time to onset of recurrence was 7.24 months (extreme 3-67.7 months). Six patients had only a neck node recurrence, 3 had a neck node and subsequent primary recurrence, and 1 had only a median subsequent primary recurrence. Only 1 patient had synchronous distance progression to local recurrence. All neck node recurrences were solitary and ipsilateral. The subsequent primary recurrences were in the oropharynx in 3 cases and in the contralateral oral cavity in one case. All neck node recurrences were into the irradiated volume. The subsequent primary recurrences were either within or in border of the irradiated volumes. The median of the mean dose, received by neck node recurrences, was 69.9 Gy and that of the mean dose, minimum dose, maximum dose, and dose received by 95% of the volume of recurrence was 66.7 Gy. For the primary relapses, the median of the mean dose was 52.1 Gy and that of the mean dose, minimum dose, maximum dose, and dose received by 95% of the volume of recurrence was 39.9 Gy. Conclusions: All local nodal recurrences occurred at sites that received high radiotherapy doses and doses received by sites of eventual failure did not vary significantly from sites that remain in control.

Resume Objectif Etude retrospective visant a evaluer l’efficacite et la tolerance de l’ajout d’une chimiotherapie neoadjuvante a la chimioradiotherapie concomitante dans le traitement du cancer du nasopharynx. Patients et methodes Les donnees de 62 patients traites pour un cancer du nasopharynx non metastatique ont ete analysees en comparant 2 groupes de patients : un 1er groupe de 32 patients traites par 3 cycles de chimiotherapie neoadjuvante a base de docetaxel, cisplatine et 5-fluoro-uracile tous les 21 jours suivie de chimioradiotherapie concomitante (cisplatine hebdomadaire 40 mg/m2 avec radiotherapie 70 Gy, 2 Gy par seance, 5 seances par semaine) et un 2e groupe de 30 patients traites par la meme chimioradiotherapie concomitante. Resultats Apres un suivi median de 53,5 mois, la chimiotherapie neoadjuvante a montre une reduction significative du taux de rechutes metastatiques a distance (3,3 % vs 10 %, p = 0,03). Aucune difference significative en termes de survie sans maladie a 5 ans (65,6 % vs 68,8 % p = 0,46) ni de survie globale a 5 ans (68,8 % vs 73,3 %, p = 0,46) n’a ete notee entre les 2 groupes. La chimiotherapie d’induction a ete associee a un taux de neutropenie febrile de 15,6 %. Au cours de la chimioradiotherapie concomitante, les complications hematologiques ont ete plus importantes dans le groupe de chimiotherapie premiere (53 % vs 33 %). Conclusion La chimiotherapie premiere type docetaxel, cisplatine et 5-fluoro-uracile est une option efficace et bien toleree dans le traitement des cancers du nasopharynx. Une meilleure definition de groupe a haut risque de rechute permettrait d’optimiser les indications de cette chimiotherapie dans l’arsenal therapeutique.

The Buschke - Lowenstein tumor is a rare sexually transmitted disease. Its location at the anal margin is also very rare. The most incriminated risk factor is human papillomavirus infection. Its clinical form may be confusing with other tumor and infectious lesions. Histologically, it is characterized by a well-differentiated malpighian proliferation. It represents local aggressive behavior. The treatment of reference remains the surgery with healthy margins of excision. Other treatments have been tested, but their effectiveness remains uncertain. We report here a new case of anal margin Buschke - Lowenstein tumor with a review of the literature.

Resume Objectif de l’etude Etude retrospective des caracteristiques anatomocliniques et des aspects therapeutiques des rechutes locales des carcinomes du nasopharynx. Patients et methodes Entre fevrier 1993 et decembre 2013, 40 patients ont ete atteints d’une recidive locale, associee ou non a une recidive ganglionnaire locoregionale. Le traitement de rattrapage consistait en une reirradiation du nasopharynx. La dose totale prescrite lors de la reirradiation etait de 60 Gy. Une chimiotherapie a base de sels de platine etait associee en cas de tumeur localement evoluee et/ou d’atteinte ganglionnaire. Resultats L’âge moyen des patients au moment du diagnostic initial etait de 41,9 ans (26–67 ans). Le delai moyen d’apparition de la rechute locale par rapport a la fin du traitement initial etait de 31,7 mois (6–104 mois). Soixante-cinq pour cent des recidives etaient exclusivement localisees au cavum. Une rechute ganglionnaire etait associee dans 14 cas. Vingt-huit patients ont recu une chimiotherapie. Vingt-cinq patients ont recu une reirradiation du nasopharynx. Avec un recul moyen de 98 mois (12–191 mois), 14 patients etaient vivants et en situation de remission complete. La probabilite de survie globale a 5 ans etait de 40,7 %. L’hyposialie etait la toxicite tardive la plus frequente. Aucune hemorragie n’a ete constatee. Conclusion La reirradiation est la pierre angulaire du traitement de rattrapage des rechutes locales des carcinomes du nasopharynx. L’incidence de la toxicite tardive semble diminuer grâce a l’apport des techniques innovantes, sans compromettre les resultats therapeutiques.

Background and purpose To assess anatomic changes during intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine its dosimetric impact. Patients and methods Twenty patients treated with IMRT for NPC were enrolled in this study. A second CT was performed at 38 Gy. Manual contouring of the macroscopic tumor volumes (GTV) and the planning target volumes (PTV) were done on the second CT. We recorded the volumes of the different structures, D98 %, the conformity, and the homogeneity indexes for each PTV. Volume percent changes were calculated. Results We observed a significant reduction in tumor volumes (58.56 % for the GTV N and 29.52 % for the GTV T). It was accompanied by a significant decrease in the D98 % for the 3 PTV (1.4 Gy for PTV H, p = 0.007; 0.3 Gy for PTV I, p = 0.03 and 1.15 Gy for PTV L, p = 0 0.0066). In addition, we observed a significant reduction in the conformity index in the order of 0.02 (p = 0.001) and 0.01 (p = 0.007) for PTV H and PTV I, respectively. The conformity variation was not significant for PTV L. Moreover, results showed a significant increase of the homogeneity index for PTV H (+ 0.03, p = 0.04) and PTV L (+ 0.04, p = 0.01). Conclusion Tumor volume reduction during the IMRT of NPC was accompanied by deterioration of the dosimetric coverage for the different target volumes. It is essential that a careful adaptation of the treatment plan be considered during therapy for selected patients.

Although its incidence has declined over last half-century, gastric cancer remains the second most frequent cause of cancer death in the world. The ⅔ of the patients are metastatic at diagnosis. The current study aimed to identify some determinants of survival in patients with metastatic gastric carcinoma. MATERIALS AND METHODS It was a retrospective study that involved 49 patients treated with palliative chemotherapy between January 2000 and December 2010. Factors included: age, gender, performance status, metastatic diagnosis onset (at diagnosis or later); specific metastatic sites, number of metastatic localizations, response to chemotherapy, and hemoglobin rate. RESULTS In univariate analysis, factors associated to a better survival were: metastasis at diagnosis, good performance status, response to chemotherapy and single metastatic site. Independent factors in multivariate analysis were: metastasis at diagnosis and single metastatic site. CONCLUSION Our study confirmed many determinants on survival described in the literature.

Purpose To define epidemiological, clinical, therapeutic and prognostic factors influencing survival of breast cancer in young women younger than 35 in southern Tunisia. Material and methods This is a retrospective study of 83 patients younger than 35 years and treated within tumors mammary committee of Sfax. Results The mean age was 31.7 years. T2 stage, high grade with positive node tumors were frequent. Breast surgery was performed for 73 patients. Chemotherapy was neo-adjuvant, adjuvant and palliative for respectively 10, 62 and 13 patients. Radiotherapy was delivered for 65 patients with curative intent and for 8 metastatic patients. Endocrine therapy was adjuvant in 38 patients and palliative in 6 cases. The overall survival (OS) at 5 years was 66.8%. Pejorative prognostic factors in uni-variate analysis were clinical T stage (T3, T4), and the number of involved lymph nodes. Conclusion Despite adequate treatment, the prognosis of breast cancer in young women remains worse. Early diagnosis is necessary to promote outcome.

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.

Resume Les cancers du cavum ont une incidence d’environ 0,5 cas par an et par 100 000 habitants pour les hommes en France, mais sont endemiques dans des regions comme l’Asie du Sud-Est. La prise en charge therapeutique par radiotherapie exclusive, qui a longtemps ete le standard, permet d’obtenir des taux de controle local pour les stades T3-T4 de l’ordre de 50 a 75 % des cas. Les techniques d’irradiation en modulation d’intensite permettent une excellente couverture dosimetrique avec une meilleure protection des organes a risque et doivent etre privilegiees. L’apport d’une chimiotherapie concomitante a l’IMRT ameliore significativement les taux de survie globale qui sont superieurs ou egaux a 75 % a cinq ans dans les stades avances. Dans la pratique courante, une radiochimiotherapie concomitante a base de sels de platine est realisee mais la place des cures neoadjuvantes et/ou adjuvantes est discutee dans le but principal de diminuer les rechutes a distance, des etudes sont en cours. Enfin, la surveillance doit etre axee sur la detection precoce de rechutes locales potentiellement curables et sur la prise en charge des sequelles therapeutiques a long terme.

Resume Objectif Etudier les caracteristiques epidemiologiques, cliniques et anatomopathologiques, ainsi que les resultats therapeutiques des lymphomes osseux primitifs localises. Patients et methodes Entre fevrier 1993 et fevrier 2013, quatre patients atteints de lymphome osseux primitif localise, ont ete pris en charge par le comite des hemopathies malignes des centres hospitaliers universitaires de Sfax en Tunisie. Les decisions therapeutiques etaient prises en reunion de concertation pluridisciplinaire prenant en consideration l’âge du patient, son etat general, le stade de sa maladie, la concentration de lactate deshydrogenase (LDH) et ses conditions socioeconomiques. Une evaluation de la reponse au traitement etait faite apres la chimiotherapie et apres la fin de la radiotherapie. La surveillance apres traitement etait clinique, biologique et radiologique Resultats L’âge moyen des malades etait de 59,5 ans. Le sex-ratio etait de 3. Les localisations osseuses etaient la clavicule, le femur, l’humerus et la mandibule. Tous les malades etaient atteints d’un lymphome B a grandes cellules de stade I. Le lymphome osseux se traduisait par une lesion osteolytique avec rupture corticale et extension aux parties molles dans trois cas. Il y avait chez un patient un aspect de fracture deplace instable de l’extremite inferieure de l’humerus droit. Le traitement a consiste en une chimiotherapie suivie d’une radiotherapie. Trois patients etaient en situation de remission complete avec un recul moyen de 76 mois. Conclusion Le traitement du lymphome osseux primitif repose sur l’association chimiotherapie (avec ou sans anti-CD20) et de radiotherapie, son pronostic est excellent quand il est localise.

Paratesticular rhabdomyosarcoma is a rare tumor. Multimodality treatment should involve surgery, radiotherapy and chemotherapy, which are indicated according to risk groups. Risk group stratification depends on pretreatment staging and definitive histology. Patients older than 10years or those with suspected lymph nodes on imaging have higher incidence of lymph node involvement. Prognosis is excellent for localized tumors, survival rates exceed 90%. We report a case of embryonal paratesticular rhabdomyosarcoma treated in our institution.

Resume Objectif Comparer les resultats therapeutiques de deux groupes de patients, adultes et enfants, traites pour un carcinome du nasopharynx. Patients et methodes Trois cents soixante-dix-sept patients atteints d’un carcinome du nasopharynx ont ete irradies entre 1993 et 2007. Parmi eux, 69 etaient âges de moins de 20 ans. Deux cent soixante-huit patients ont recu une chimiotherapie neoadjuvante ou concomitante. Resultats Les probabilites de survie globale et de survie sans progression de tout le groupe a cinq ans etaient respectivement de 67 % et 59,4 %. Celles de survie globale a cinq ans etaient respectivement de 66 % et 64 % (p = 0,17) dans le groupe enfants et adultes, celles de survie sans progression a cinq ans de 66 % et 57 % (p = 0,17). Les rechutes etaient plus frequentes chez les adultes (1,4 % contre 14 %), mais les rechutes metastatiques etaient plus frequentes chez les enfants. La toxicite tardive etait plus marquee chez les enfants et representee essentiellement par la xerostomie, sans difference significative. Conclusion Les resultats therapeutiques etaient meilleurs dans le groupe des enfants malgre la frequence des formes localement evoluees, sans atteindre le seuil de signification. L’association de radiotherapie et de chimiotherapie pourrait expliquer nos resultats therapeutiques.

The extranodal non-Hodgkin lymphomas of maxillofacial soft tissues are rare. We report two cases of maxillofacial soft tissue non-Hodgkin lymphoma treated with chemotherapy followed by localized radiotherapy with complete remission after 3 and 6 months. We study the clinical, radiological and histopathological features as well as the treatment and the prognosis of extranodal non-Hodgkin lymphomas maxillofacial muscles.

BACKGROUND: Mammary neuroendocrine carcinoma (NEC) displays morphological features including mucinous type. OBJECTIVE: To describe clinicopathological of NEC with mucinous differentiation. METHODS: A total of 15 cases of mammary NEC with mucinous differentiation were reviewed. RESULTS: All patients in this study were women aged from 37 to 78 year olds (median 68.1 years). The tumors ranged in size from 1.2 cm to 16 cm (mean 3.74 cm). The amount of extracellular mucin varied from 10% to 90%. Histological grade was I in 7 cases and II in 8 cases. Immunohistochemically, estrogen receptor (ER) and progesteron receptor (PR) were expressed in 12 and 14 cases, respectively. All tumors were negative for Her-2. Ki-67 proliferative index was lesser than 1% in all cases and no cases had demonstrated p53 overexpression. Three patients died of disease with a follow-up of 3 to 6 months. One patient was alive with metastasis at 96 months. Ten patients were disease free (follow-up range from 15 to 125 months). CONCLUSIONS: Mammary NEC with mucinous differentiation affects mostly older women. All tumors were low grade and immunoreactive for ER/PR and negative for Her-2. Mammary NEC with mucinous differentiation seems associated with well survival parameters.

We report the case of a long survival after the treatment of a squamous cell carcinoma of the gallbladder. The patient is a 58-year-old man, who was treated by cholecystectomy, followed by postoperative radiotherapy of the tumour bed at a dose of 45Gy, combined with 5-fluoro-uracil chemotherapy. After 18 years, the patient is alive in complete remission. The end point of this work was to study the clinical and therapeutic characteristics of squamous cell carcinoma of the gallbladder and its prognosis through this case and a review of literature.

Tumour suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer initiation. The aim of this study was to assess the extent of methylation of APC gene promoter in 91 sporadic and 44 familial cases of Tunisian patients with breast cancer (BC) in. The frequency of APC promoter methylation is somewhat similar for sporadic and familial breast cancer cases, (52.1%, and 54.5% respectively). For sporadic breast cancer patients, there was a significant correlation of APC promoter hypermethylation with TNM stage (p = 0.024) and 3-year survival (p = 0.025). Regarding the hormonal status (HR), we found significant association between negativity to PR and unmethylated APC (p= 0.005) while ER and Her2/neu are not correlated. Moreover, unmethylated APC promoter is more frequent in tumours expressing at least one out the 3 proteins compared to triple negative cases (p= 0.053). On the other hand, aberrant methylation of APC was associated with tumour size (p = 0.036), lymph node (p = 0.028), distant metastasis (p = 0.031), and 3-year survival (p = 0.046) in the group of patients with familial breast cancer. Moreover, patients with sporadic breast cancer displaying the unmethylated profile have a significant prolonged overall survival compared to those with the methylated pattern of APC promoter (p log rank = 0.008). Epigenetic change at the CpG islands in the APC promoter was associated with the silence of its transcript and the loss of protein expression suggesting that this event is the main mechanism regulating the APC expression in breast cancer. In conclusion, our data showed that the loss of APC through aberrant methylation is associated with the aggressive behavior of both sporadic and familial breast cancer in Tunisian patients.

Background: The Ewing sarcoma (ES) represents 10 to 15% malignant bone tumors and 40 to 45% pediatric malignant bone tumors. The aim of this review is to clarify the therapeutic results and prognostic factors of this entity. Methods: A systematic review of the literature was performed. Studies focused on the management of ES were considered for inclusion. Result: ES represents a model of multidisciplinary approach. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between the pediatric and medical oncologists. The overall 5- year survival of Ewing localized tumors was 70% versus 30% in metastatic ES. Conclusion: The treatment of ES includes neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The role of high-dose chemotherapy is still debated.

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.

The prognosis of breast carcinoma is related to a large variety of clinical and pathological factors. Currently, only oestrogen (ER) and progesterone (PR) receptors and human epidermal growth factor receptor 2 (HER2) are used in routine pathological assessment as biomarkers. The aim of this study was to evaluate the prognostic impact of epidermal growth factor receptor (EGFR) expression individually and in combination to classical biomarkers (HER2, ER, and PR), and its relation to tumors with triple negative profile in Tunisian breast carcinoma.Immunohistochemistry was used to estimate the rate expression of these receptors. Univariate and multivariate analyses were used to explore the prognostic significance of EGFR in this study.The expression rate of EGFR was 28.6%. EGFR expression was inversely correlated to that of ER (P0.001). Significant correlations between the expression of EGFR and the high histological Scarff-Bloom-Richardson (SBR) grade (P = 0.038) and also with tumors size (P = 0.041) were observed. The triple negative profile (TN: ER-/PR-/HER2-) was present in 17.3% of cases. EGFR overexpression was positively associated with this clinical aggressive profile (P0.001). Survival analysis showed that EGFR expression was associated with poor survival of patients (P = 0.004). In multivariate analysis, EGFR expression (P = 0.035) was found to be independent prognostic factors (significantly correlated to survival).EGFR overexpression was observed in 28.6% of Tunisian breast carcinoma, associated with unfavorable prognosis and with triple negative tumors. Systemically evaluation of EGFR in breast carcinoma could benefit especially to TN subgroup from EGFR targeting agents.

Objectif de l’etude L’objectif etait de developper et de valider un programme sous Matlab pour l’analyse des fichiers dynalog-Varian dans le cadre de la mise en œuvre d’une procedure de controle de qualite de routine des plans de traitements par irradiation avec modulation d’intensite. Materiel et methode Nous avons utilise des fichiers dynalog qui sont enregistres tous les 50 ms par le controleur du collimateur multilames Millennium 80 de Varian afin de suivre en temps reel le bon deroulement des radiotherapies dynamiques. Ces fichiers contiennent plusieurs informations relatives aux parametres d’irradiation : la dose, les positions des lames planifiees et reelles, l’angle du bras et du collimateur. Nous avons opte pour Matlab qui est un logiciel tres productif pour l’analyse des donnees, le programme est concu pour l’utilisation des fichiers dynalog et la quantification des erreurs relatifs aux positionnements des lames, les erreurs du gap et de vitesse. Nous avons etudie 250 fichiers dynalog relatifs a des patients traites par modulation d’intensite pour des tumeurs de la prostate. Resultats Plus de 99 % des lames presentent des erreurs inferieures a 1 mm. Des erreurs entre 1 et 1,5 mm ont ete detectees dans certains cas ; le programme permet de mettre en evidence la lame presentant un seuil d’erreur fixe par l’operateur. La vitesse des lames est de l’ordre de 20 mm/s ; une acceleration ou un ralentissement explique aussi une erreur dans la position des lames. Les erreurs des positions de lames varient en fonction de l’angle du bras a cause du de la gravite. Conclusion Le developpement d’un programme d’analyse des fichiers dynalog est un outil simple et efficace pour l’evaluation de la qualite de realisation des plans dynamiques.

Infiltrating ductal carcinoma (IDC) of the breast is a result of genetic alterations that affect the regulation of the cell cycle check-point and apoptosis. The aim of the present study was analysis using immunohistochemical localization of mouse double minute-2 (mdm2), p16INK4a, p53, bax and bcl-2 markers in Tunisian patients with breast IDC and to determine if there was correlation with the major clinico-pathological parameters and with survival of patients. We showed that the expression of p53, p16INK4a, mdm2, bcl-2, and bax was observed in 46.3%, 20.7%, 38%, 50% and 11.9% of cases, respectively. Statistical analysis revealed that positive expression of mdm2 was associated with larger tumors (P=0.013), whereas bax positivity was more prevalent in younger patients and in tumors of smaller size (P=0.008 and P=0.012 respectively). Furthermore, the expression of p16INK4a correlated with advanced grade (P0.0001), triple negative tumors (ER-/PR-/HER2-, P=0.001) and mdm2 expression (P=0.017). The absence of nuclear p53 accumulation was predictive of good prognosis as well as when it was associated with negative expression of p16INK4a. Our findings suggest that among the biomarkers tested, p16INK4a might have a useful clinical and prognostic significance in infiltrating ductal carcinoma of the breast.

Obesity is associated with worse breast cancer outcomes in Western and Asian women. The present study was to determine the relation of body mass index (BMI) to disease-free survival (DFS) in Tunisian patients with operable breast cancer. We retrospectively reviewed data from 223 patients with operable breast cancer treated with primary surgery and adjuvant epirubicin-based chemotherapy. Patients were categorized into lower-BMI (2; N=114) v higher-BMI (>27.5 kg/m2; N=113). Patients’and disease characteristics, including tumor size and lymph node status, were similar between the 2 groups. With a median follow-up of 56 months, there were 42 and 30 DFS events in the lower- and higher-BMI group, respectively (adjusted hazard ratio (HR): 0.74; 95% CI, 0.43 to 1.26; p=0.26). A significant interaction (p

Many biomarkers for breast cancer prognosis have been proposed during the last two decades, among which HER2 and oestrogen receptors are of common use in routine clinical practice. However, in recent years, BCL2 has been recognized as an important prognostic parameter in human breast cancer, although its clinical utility is well established. The aim of this study was to examine the protein expression patterns of BCL2, HER2, oestrogen (ER) and progesterone receptors (PR) and to evaluate their correlation with survival and other prognostic parameters such as tumour size, histological grade and metastasis. We used a retrospective study including 84 Tunisian women with breast cancer. Immunohistochemistry was used to measure protein expression levels of several biomarkers. Association with conventional biopathological factors was analysed by SPSS (version13). The expression rates of BCL2, HER2, ER and PR were, respectively, 69, 62, 58.3 and 51.2%. In univariate analyses, BCL2 was highly correlated with both PR (P < 0.001) and ER (P = 0.006) and also with HER2 expression (P = 0.001). The triple negative profile showed a significant association with SBR (P = 0.016) and BCL2 expression (P = 0.02). In multivariate analyses, a significant association was maintained between BCL2 and both PR and ER (P = 0.02 and P = 0.004, respectively). Survival analysis showed that BCL2 expression was positively correlated with patients survival (P = 0.032). A Bayesian network analysis of all the variables confirmed the high value of BCL2 expression as a predictor of survival. As conclusion, BCL2 expression seems to be a very useful factor that should be in combination with HER2 and ER in breast cancer prognosis.

Resume Objectif de l’etude La mesure de la dose delivree en cours d’irradiation est un element cle du controle de qualite en radiotherapie. L’objectif de ce travail etait, d’une part, de mesurer la dose a l’entree des faisceaux d’irradiation lors du traitement des cancers des voies aerodigestives superieures et, d’autre part, de la comparer avec la dose calculee. Patients et methodes Vingt patients ont ete l’objet de cette evaluation. Dans un premier temps, une etude sur fantome a ete realisee afin d’etalonner et de determiner les differents facteurs de correction des diodes utilisees pour la dosimetrie in vivo. La mesure de la dose a l’entree a ete effectuee pour tous ces patients qui sont traites dans des conditions de traitement isocentrique par deux faisceaux lateraux opposes de photons gamma de 60Co. Resultats La dosimetrie in vivo a ete pratiquee pour 100 faisceaux. L’analyse des resultats obtenus a montre que l’ecart moyen entre la dose mesuree a l’entree et la dose calculee etait de 0,12 %, avec un ecart type de 1,84 %. Dans 95 % des mesures, l’ecart etait inferieur a 3 %. Pour un seul faisceau, l’ecart entre la dose mesuree et la dose calculee etait superieur a 5 %. Conclusion Les erreurs dues aux operations humaines et aux defaillances techniques et informatiques sont de nature aleatoire ou systematique. La dosimetrie in vivo permet de prevenir ces erreurs et d’en limiter la frequence.

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.

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.

The mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct clinical pathologic entity that develops in diverse anatomic locations such as the stomach, salivary gland, thyroid, lung, skin and breast. However, colorectal involvement is extremely rare. To our knowledge, only ten cases of primary rectal MALT lymphoma have been reported in the literature. We report a 46-year-old woman with rectal MALT lymphoma, which regressed after radiotherapy. The patient had rectal bleeding. Colonoscopy showed a pseudonodular and ulcerated big fold in the rectum. Microscopic and immunohistologic studies of the biopsy specimen showed typical features of low grade MALT lymphoma. Upper endoscopy showed chronic gastritis with lymphoid follicles but without any infiltration of lymphoma cells. Helicobacter pylori infection was confirmed by histology. No extra-intestinal involvement was found on the staging evaluation, which included computed tomography (CT) of the abdomen, chest, pelvis and a bone marrow biopsy. We attempted to eradicate H. pylori with a 7-day course of omeprazole, amoxycillin, and metronidazole. Eradication was proved successful by endoscopy. Repeated colonoscopy 4 months after the end of treatment showed that the rectal tumor had not regressed. Biopsy specimens confirmed the persistent infiltration of lymphoma cells. The patient was considered to be a non-responder to eradication therapy and was indicated for radiotherapy. He underwent a total of 34 Gy. Complete regression was confirmed by colonoscopic and histologic examination at 2 months after the end of treatment. He was followed up closely with colonoscopy, but no relapse of these lesions was detected after 12 months.

Background Breast cancer is the most frequent malignant neoplasm affecting Tunisian women. It represents 25 to 35% of all female cancers. There is no published study about the features of Her-2 overexpressing breast carcinomas in North African women. Objective The aim of this study is to assess the prognostic significance of pathological features in a cohort of a Her-2 overexpressing breast carcinoma originating from the region of south Tunisia. Methods This study investigated a series of 100 patients followed from January 2006 to December 2011 for a Her-2 positive invasive breast carcinoma. Pathological features included in this study were: histological type, histological grade, tumor size, vascular invasion, perineural invasion, mitotic index, lymph nodes stage, positive lymph node capsular effraction, inflammatory infiltrates, nipple involvement and hormone receptors status. Results Multivariate analysis showed that pT stage, pN stage, capsular effraction, vascular invasion, perineural invasion and Nipple involvement were independent prognostic factors for overall survival and disease free survival in patients free from distant metastasis at diagnosis. For patients with synchronous metastasis, there is no independent pathologic prognostic factor for survival. Conclusions Our study demonstrates that pathological features are important prognostic factors for non metastatic Her-2 overexpressing breast carcinomas. This supports the idea that HER2-positive disease is a heterogeneous entity. We believe that these findings reinforce the need to identify molecular predictors of benefit and resistance to anti-Her-2 based therapies.

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 ⩽20 years (mean age 15 years) were treated in our institution; they represented 18% of all NPC cases seen during the same time period. 27 patients had no metastases at diagnosis; 26 of these were treated with primary chemotherapy combining epirubicin and cisplatin. Radiotherapy was then delivered to 22 patients at a mean dose of 70 Gy, either conventionally (6 patients) or bifractionated (16 patients). 5 patients had metastases at diagnosis and were treated with chemotherapy combining epirubicin, bleomycin and cisplatin before definitive radiotherapy. The objective response rate (OR) after chemotherapy was 90.9% at the primary site, with a 13.6% complete response (CR) rate. At nodal sites, the OR was 95.5% and the CR was 31.8%. Local control was obtained in all patients after definitive radiotherapy with a medium follow-up of 43.7 months. Late toxicity affecting quality of life was found in 26% of the children who were irradiated, especially among those under 15 years of age (skin fibrosis, 27%; trismus, 27%; hypothyroidism, 14%). No locoregional relapses were observed. Distant metastases occurred in 33% of cases, with a median delay of 4.7 months from the end of treatment. The 2- and 5-year overall survival (OS) rates were 76 and 56%, respectively. Disease-free survival (DFS) was 65% at 2 and 5 years. Therapeutic outcomes for childhood NPC were similar to those in adults, but with more radiotherapy-induced toxicity. New chemotherapeutic combinations and new radiotherapeutic techniques should be sought to improve both survival and quality of life.

Resume Objectif. – Le dysfonctionnement de la glande thyroidienne apres radiotherapie nous a conduit a evaluer la dose recue par celle-ci lors de l’irradiation cervicale pour un cancer du cavum et l’irradiation susclaviculaire pour un cancer du sein en utilisant la dosimetrie in vivo a semiconducteurs. L’objectif de ce travail etait d’une part d’evaluer la dose recue au parenchyme thyroidien et d’autre part, de la comparer a la dose delivree au point de reference du volume cible des 2 localisations. Patients et methodes. – Trente patients ont ete l’objet de cette evaluation, dont 18 sont traites pour un cancer du cavum et 12 pour un cancer du sein. Dans le premier cas, la thyroide etait irradiee en totalite, a l’exception de l’isthme, mais dans le second, un seul lobe thyroidien faisait partie du volume irradie. Tous les malades ont ete irradies par un appareil de telecobaltherapie et, par consequent, les dosimetres utilises etaient de type DPD6 et etalonnes individuellement dans les conditions d’irradiation. Resultats. – L’analyse des resultats de la dosimetrie in vivo a montre que la dose mesuree au niveau du parenchyme thyroidien etait de 100,8 % de la dose prescrite specifiee a –3 cm de profondeur de la region cervicale, soit 44,3 Gy en cas de cancer du sein et 51,9 Gy en cas de cancer du cavum. La dose au niveau de l’isthme cache etait de 5,03 ± 1,08 Gy (10,07 ± 2,18 %), 5,1 ± 0,9 Gy (9,9 ± 1,8 %) et 3,7 ± 0,77 Gy (8,4 ± 1,76 %), respectivement dans le cas du cancer du cavum. La dose au niveau du lobe controlateral au champ susclaviculaire dans le cas du traitement du cancer du sein etait de 2,9 ± 0,7 Gy (6,55 ± 1,55 %). Conclusion . – Cette etude nous montre que le parenchyme thyroidien, considere comme organe a risque, recoit une dose voisine de celle prescrite au niveau du volume cible des deux types de cancer si elle fait partie de ce volume. Par consequent, il est necessaire de faire une surveillance reguliere des patients, traites par irradiation pour ces deux tumeurs, a la recherche d’un deficit fonctionnel de la glande thyroidienne.

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 −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.