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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.

This study aimed to explore the treatment modalities of relapsed osteosarcoma, treatment results, and prognostic factors.We conducted a retrospective study of patients treated for relapsed osteosarcoma between 2005 and 2019. Patient survival was compared according to age, performance status, time to relapse, and surgical treatment at the relapse. Values of p0.05 were considered to indicate statistical significance.We included 49 patients who were treated for osteosarcoma. During the 13-year study period, 16 patients had relapsed osteosarcoma (32.7%). Prognostic factors of relapse were age over 18 years (p = 0.03), axial tumors (p = 0.01), and positive surgical margins (p = 0.018). Nine patients had palliative chemotherapy at the time of relapse. After a median follow-up of 8 months (range: 4-65 months), the overall survival at 1 year, 2 years, and 5 years after diagnosis of the relapse was 46.7%, 31.1%, and 20.7%, respectively. Relapsed osteosarcoma patients who had good performance status, late relapse (after 12 months), as well as surgery of the relapsed disease had better overall survival (OS).Surgical treatment of relapsed osteosarcoma should be performed whenever possible since it improves significantly the survival of patients. Good performance status and late relapse were also associated with better survival.

(1) Background: Germline variants in BRCA1/BRCA2 genes explain about 20% of hereditary breast/ovarian cancer (HBOC) cases. In the present paper, we aim to identify genetic determinants in BRCA-negative families from the South of Tunisia. (2) Methods: Exome Sequencing (ES) was performed on the lymphocyte DNA of patients negative for BRCA mutations from each Tunisian family with a high risk of HBOC. (3) Results: We focus on the canonical genes associated with HBOC and identified missense variants in DNA damage response genes, such as ATM, RAD52, and RAD54; however, no variants in PALB2, Chek2, and TP53 genes were found. To identify novel candidate genes, we selected variants harboring a loss of function and identified 17 stop-gain and 11 frameshift variants in genes not commonly known to be predisposed to HBOC. Then, we focus on rare and high-impact genes shared by at least 3 unrelated patients from each family and selected 16 gene variants. Through combined data analysis from MCODE with gene ontology and KEGG pathways, a short list of eight candidate genes (ATM, EP300, LAMA1, LAMC2, TNNI3, MYLK, COL11A2, and LAMB3) was created. The impact of the 24 selected genes on survival was analyzed using the TCGA data resulting in a selection of five candidate genes (EP300, KMT2C, RHPN2, HSPG2, and CCR3) that showed a significant association with survival. (4) Conclusions: We identify novel candidate genes predisposed to HBOC that need to be validated in larger cohorts and investigated by analyzing the co-segregation of selected variants in affected families and the locus-specific loss of heterozygosity to highlight their relevance for HBOC risk.

Objectives: Several new cancer therapies targeting signaling pathways involved in the growth and progression of cancer cells were developed as personalized medicine. Our study aimed to identify epidermal growth factor receptor (EGFR) mutations for TKI treatment in non-small-cell lung cancer (NSCLC) Tunisian patients. Methods: Analysis of the TKI sensitivity mutations in exons 18 to 21 of the EGFR gene and exon 15 of the B-raf gene was performed in 79 formalin fixed-paraffin embedded (FFPE) NSCLC samples using pyrosequencing. Results: EGFR mutations were detected in 34 cases among 79 (43%), with the predominance of the L861Q in exon 21 found in 35.3% of the cases (12 out of 34). Deletions in exon 19 were found in 8 cases (23.5%), and only one young male patient had the T790M mutation. Three patients harbored composite EGFR mutations (p.E746_A750del/p.L861R, p.E746_S752>V/p.S768I, and p.G719A/p.L861Q). Furthermore, the EGFR mutated status was significantly more frequent in female patients (p = 0.019), in non-smoker patients (p = 0.008), and in patients with metastasis (p = 0.044). Moreover, the B-raf V600E was identified in 5 EGFR negative patients among 39 analyzed samples (13.15%). Conclusion: The p.L861Q localized in exon 21 of the EGFR gene was the most common mutation identified in our patients (35.3%), whereas the “classic” EGFR mutations such as Del19 and p.L858R were found in 23.5% and 11.7% of the cases, respectively. Interestingly, most of p.L861X mutation-carrying patients showed good response to TKI treatment. Altogether, our findings suggest a particular distribution of the EGFR-TKIs sensitivity mutations in Tunisian NSCLC patients.

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.

Background Cardiotoxicity following breast cancer radiotherapy (RT) represents one of the most redoubtable toxicities. The Global longitudinal strain measurement (GLS) based on 2D speckle tracking imaging (STI) allows detection of left ventricular (LV) dysfunction at a subclinical stage. The aim of this prospective study was to detect patients at risk of cardiotoxicity using echocardiographic parameters and to determine the association between segmental RT doses and early cardiac toxicity. Material and methods The STI was performed prior to RT and at 3, 6 and 12 months after. The association between subclinical LV dysfunction, defined as a reduction of GLS more than 10% from the initial value, radiation doses to different LV segments and non-radiation factors were performed based on multivariate analyses. Results From June 2017 to August 2018, a total of 103 female patients were included. Sixty patients had left sided RT. Seven patients (7.8%) developed a GSL impairment. The segmental alterations predominated in the anteroseptal and apical LV segments. The mean Dmean in altered segments was significantly higher than in non-altered segments (6.7 ± 8.8Gy-7.8 ± 8.9Gy vs 4.9 ± 7.9–5.4 ± 8.2Gy; p 55 years and obesity were important confounding factors that should be considered during radiotherapy planning. Conclusion The results of our study show that radiation dose is correlated with the subclinical LV segments' alteration. Global heart delineation seems to be insufficient during the breast radiotherapy planning. Segmental delineation of the LV may be an interesting alternative to limit segmental doses and to reduce the risk of subclinical alterations. A mean dose of 5Gy could be proposed in exposed heart segment.

This paper presents a new system for predicting the spatial change of Nasopharyngeal carcinoma(NPC) and organ-at-risks (OARs) volumes over the course of the radiation therapy (RT) treatment for facilitating the workflow of adaptive radiotherapy. The proposed system, called “Tumor Evolution Prediction (TEP-Net)”, predicts the spatial distributions of NPC and 5 OARs, separately, in response to RT in the coming week, week n. Here, TEP-Net has (n-1)-inputs that are week 1 to week n-1 of CT axial, coronal or sagittal images acquired once the patient complete the planned RT treatment of the corresponding week. As a result, three predicted results of each target region are obtained from the three-view CT images. To determine the final prediction of NPC and 5 OARs, two integration methods, weighted fully connected layers and weighted voting methods, are introduced. From the experiments using weekly CT images of 140 NPC patients, our proposed system achieves the best performance for predicting NPC and OARs compared with conventional methods.

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: The incidence of breast/ovarian cancer is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region. Methods: We sequenced the entire coding regions of BRCA1and BRCA2 genes using Next Generation Sequencing (NGS) in 134 selected patients with breast/ovarian cancer. Results: Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshisft indel (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 in BRCA2 and 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 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A>T, (K3326*) in BRCA2 exon 27. BRCA carriers correlated significantly with tumor site (p=0.029) and TNBC cases (p=0.008). In the groups of patients (31-40 y and 41-50 y), BRCA1 mutations occurred more frequently in patients with OC than those with BC, and conversely BRCA2 carriers are mostly affected with BC (p=0.001 and p=0.044 respectively).Conclusions: The 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 in BRCA2 gene and the c.5030_5033 delCTAA in BRCA1 gene 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 breast/ovarian cancer.

In this paper, we propose a method for predicting dose distribution images of patients with Nasopharyngeal carcinoma (NPC) from contoured computer tomography (CT) images. The proposed system is based on our previous method [1]. The first phase is to obtain the feature maps of 2D dose images of each beam from contoured CT images of a patient by convolutional deep neural network model. In the second phase, dose distribution images are predicted from the obtained feature maps by the integration network. Our modified system predicted dose distribution images accurately. From the experimental results using 80 NPC patients' images, the average number of pixels that satisfy the dose constraints of tumors and OARs regions is 81.9 % and 86.1 %, respectively. The proposed system had a global 3D gamma passing rates varying from 82.1 % to 97.2 % for all regions and an overall mean absolute errors (MAEs) was 1.0 ±1.2. From the obtained results, our modified system is superior to the results obtained in our previous system results and conventional methods. Contribution-The use of the predicted 7-beam weights, as input, into our CNN network leads to improve the predicted dose distribution. Contribution-The use of the predicted 7-beam weights, as input, into our CNN network leads to improve the predicted dose distribution.

The HER2 receptor (Human Epidermal Growth Receptor 2) is a transmembrane receptor with tyrosine kinase activity that is over-expressed in 25-30 % of breast carcinomas. Its activation is associated with an exaggeration of cell proliferation with an increase in repair capacity resulting in increased radioresistance. On cardiac tissues, HER2 receptor activation plays a cardio-protective role. Trastuzumab, the first anti-HER2 drug used to treat patients with breast cancer overexpressing HER2 receptor , inhibits the cascade of reactions resulting in the proliferation of tumor cells, thus restoring cellular radiosensitivity. However, the combination of Trastuzumab with radiation therapy also removes HER2 receptor cardio-protective role on myocardial cells which increases the risk of cardiotoxicity. Thus, the concomitant association of these two modalities has long been a subject of controversy. Recent advances in radiation therapy technology and early detection of cardiac injury may limit the cardiotoxicity of this combination. Through this review, we developed the biological basis and the benefit-risk of concomitant combination of radiotherapy and Trastuzumab in adjuvant treatment of breast cancers overexpressing HER2 and we discuss the modalities of its optimization.

Male Breast Cancer (MBC) is a rare and aggressive disease that is associated with genetic factors. Mutations in BRCA1 and BRCA2 account for 10% of all MBC cases suggesting that other genetic factors are involved. The aim of the present study is to screen whole BRCA1 and BRCA2 exons using the Ampliseq BRCA panel in Tunisian MBC patients with family history. Furthermore, we performed exome sequencing using the TruSight One sequencing panel on an early onset BRCA negative patient. We showed that among the 6 MBC patients, only one (MBC-F1) harbored a novel frameshift mutation in exon 2 of the BRCA2 gene (c.17-20delAAGA, p.Lys6Xfs) resulting in a short BRCA2 protein of only 6 amino-acids. We selected 9 rare variants after applying several filter steps on the exome sequencing data. Among these variants, and based on their role in breast carcinogenesis, we retained 6 candidate genes (MSH5, DCC, ERBB3, NOTCH3, DIAPH1, and DNAH11). Further studies are needed to confirm the association of the selected genes with family MBC.

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.

The forkhead box (FOXA) family of transcription factors regulates gene expression and chromatin structure during tumorigenesis and embryonic development. Until now, the relationship between FOXA1 and the nasopharyngeal carcinoma (NPC) has not yet been reported. Therefore, our purpose is to analyze the expression of FOXA1 in 56 NPC patients compared to 10 normal nasopharyngeal mucosae and to correlate the expression with the clinicopathological features. Besides, we investigated the association between FOXA1 and LMP1 gene expression, as well as the EMT markers namely the E-cadherin and Twist1. Among 56 NPC tissues, 34 (60.7%) cases were positive for FOXA1. Furthermore, we noticed that FOXA1 expression correlated with TNM (p=0.037), and age at diagnosis (p=0.05). Moreover, positive expression of FOXA1 is likely to be associated with prolonged disease-free survival and overall survival rates. On the other hand, we observed a positive association between the expression of E-cadherin and FOXA1 (p=0.0051) whereas Twist1 correlated negatively with FOXA1 (p=0.004). Furthermore, knowing that LMP1 plays a key role in the pathogenesis of NPC, we explored the association of FOXA1 with the LMP1 gene expression in both NPC cell lines and tissues. We found that, in the C666-1 which displays low levels of LMP1, the expression of FOXA1 is high, and inversely in the C15 cell line that expresses a high level of LMP1, the level of FOXA1 is low. Besides, in accordance to our results, we found that in NPC tissues there is a negative association between LMP1 and FOXA1. In conclusion, our results suggest that the overexpression of FOXA1 is associated with a nonaggressive behavior and favorable prognosis in NPC patients. FOXA1 could contribute in the EMT process through key factors as E-cadherin, Twist1, and LMP1.

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.

Ewing's sarcoma is a malignant tumor that mainly affects young patients. It represents 10% of primary malignant tumors of the bone and 3% of malignant tumors of the child. Cranial localization is extremely rare representing less than 1% of all the localizations. We report a case of a 10-year-old girl who presented with an intracranial hypertension syndrome with left parietal mass of progressive installation. The X-ray skull showed a lytic lesion with irregular margins involving the left parietal bone. Brain magnetic resonance imaging revealed extensive parietal bone destruction involving both the inner and outer tables. The girl was operated in emergency. Histological examination concluded to Ewing's Sarcoma. The resection was incomplete (R1). The girl received induction's chemotherapy. The cerebral scanner evaluation showed no abnormalities. Then, she received consolidation's chemotherapy with concomitant local radiation therapy. Currently, the girl is in complete remission with a seven-month decline.

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.

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.

In the paper, we propose a new deep learning-based method for segmenting nasopharyngeal carcinoma (NPC) in the nasopharynx from three orthogonal CT images. The proposed method introduces a cascade strategy composed of two-phase manners. In CT images, there are organs, called non-target organs, which NPC never invades. Therefore, the first phase is to detect and eliminate non-target organ regions from the CT images. In the second phase, NPC is extracted from the remained regions in the CT images. Convolutional neural networks (CNNs) are applied to detect non-target organs and NPCs. The proposed system determines the final NPC segmentation by integrating three results obtained from coronal, axial and sagittal images. Moreover, we construct two CNN-based NPC detection systems using one kind of overlapping patches with a fixed size and various overlapping patches with different sizes. From the experiments using CT images of 70 NPC patients, our proposed systems, especially the system using various patches, achieves the best performance for detecting NPC compared with conventional NPC detection methods.

In Intensity-modulated radiation therapy, the planning of the optimal dose distribution for a patient is a complex and time-consuming process. This paper proposes a new automatic method for predicting of dose distribution of Nasopharyngeal carcinoma (NPC) from contoured computer tomography (CT) images. The proposed method consists of two phases: (1) predicting the 2D optimal dose images of each beam from contoured CT images of a patient by convolutional deep neural network model, called OTNet, and (2) integrating the optimal dose images of all the beams to predict the dose distribution for the patient. From the experiments using CT images of 80 NPC patients, our proposed method achieves a good performance for predicting dose distribution compared with conventional predicted dose distribution methods.

Introduction Breast cancer and pregnancy is rare. It is defined by the discovery of breast cancer during pregnancy or within one year after delivery. Throughout this study, we analyzed the characteristics of this entity with review of the literature. Materials and methods We report through a retrospective study of breast cancer in pregnant women, a series of 11 cases collected at the oncology department in Sfax between 1994 and 2012. Result The average age of our patients at diagnosis was 35 years. The average term of pregnancy was 22 weeks. Nine cases were diagnosed during pregnancy. The pregnancy outcome was well with babies in a good health, in 10 cases. The prognosis was excellent with complete remission after a mean follow of 39 months in 7 cases (2years-9years). Conclusion The diagnosis of breast cancer in pregnant women is often delayed because of physiological changes of pregnancy and the young age which explain the poor prognosis of this entity. The prognosis was excellent in our series compared to the literature.