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Background: We aimed to describe clinico-pathological characteristics and differences between rightsided (RCC) and left-sided colon cancer (LCC) in Tunisian population. We also analyzed outcome to determine whether location is of prognostic significance. Methods: Clinico-pathological characteristics and Kaplan Meier survival were compared between two groups of LCC [150] and RCC [53] patients with stage II and III adenocarcinoma treated with curative intent between 2003–2014. Results: RCC patients were significantly more likely to be female, (56.6% vs . 39.3%, P=0.029) and to have undifferentiated tumor (87.1% vs . 8.4%, P=0.014), then LCC. After a median follow up of 49 months, 5-year overall survival (OS) was significantly worse in RCC vs . LCC [42% vs . 78%; hazard ratio (HR) =2.07; 95% CI: 1.05–4.09; P=0.03], no difference in relapse free survival (RFS) was observed. Median time to relapse was significantly shorter in RCC (15 months) vs . LCC (24 months), P=0.005. Tumor location significantly impacted survival in stage III, 5-year OS was 45% in RCC, and 63% in LCC, (HR =2.28; 95% CI: 1.01–5.24; P=0.04), there was no impact of tumor location in stage II, (HR =1.94; 95% CI: 0.54–6.93; P=0.29). Conclusions: Prognostic impact of tumor location should be considered as a stratification factor in the future clinical trials.

Background Male breast cancer (MBC) is a rare and neglected disease. Prognostic and predictive factors in MBC are extrapoled from trials conducted on its female counterpart. Objective Since the relationship between the transcription factor Forkhead box M1 (FOXM1) expression and the clinical response to chemotherapy and hormonotherapy in MBC remains unknown, we sought to investigate the predictive value of FOXM1 in MBC. Methods FOXM1 expression was assessed in 130 MBC cases. Clinical significance was analyzed by Kaplan Meier curves, log-rank test and multivariate Cox regression analyses. Results Patients with high FOXM1 expression had a significantly lower response rate to chemotherapy (P = 0.045) and hormonotherapy (P = 0.029) than those with low FOXM1 expression. Multivariate analyses indicated that FOXM1 was an independent prognostic factor for disease free survival in MBC patients (P Conclusions FOXM1 may have a reliable predictive significance in male breast cancer and thus may become an important target for male breast cancer therapy in the near future.

Aim: We reported anatomo-clinical features of brain metastases (BMs) collected in a Tunisian medical oncology department. Patients & methods: We retrospectively identified all cases of BM within a cohort of 7055 patients, treated for a histologically confirmed nonhematological cancer between 2000 and 2016. Data about age, sex and primary tumor were collected. Results: Incidence was 1.9% and mean age was 54 years with a 1.24 sex ratio. BMs were symptomatic in 73.7% of cases after a median time of 16 months. A total of 73.4% patients receiving local therapy, 88% by whole brain radiation therapy and 21.6% had a metastasectomy. Lung and breast cancers were the primary in 80% of the BM. Conclusion: BM showed trends of young with underestimated incidence.

Background: We aimed to describe characteristics of acute pain related to port-a-cath implantation (PACI) in an oncology department. Methodology: We prospectively followed 145 patients who received PACI under local anesthesia. Our study asked patients to rate their pain according to a numerical scale immediately after implantation and within 72 hours. Patient and disease characteristics, PACI data, pain peak, and need for analgesic agents were collected. Patients already taking painkillers were excluded. Results: Median age was 55 years (range = 28–83 years) and 71% were women. Pain after PACI was rated mild by 52.4%, moderate by 35.9%, and severe by 11.7% of patients. Pain peaks were described during introducer insertion (40.7%), venous puncture (23.4%), anesthesia (18.6%), tunneling (5.9%), and suturing (1.4%). Patients with severe pain were significantly more frequently women and had a fast heart rate (≥120 bpm) before PACI (94.1% vs. 68% [P = .018] and 11.8% vs. 3.9% [P = .021], respectively). Within 72 hours of PACI, 56% of patients experienced no pain, 24.1% had mild pain, 6.2% had moderate pain, and 10.3% had severe pain. All patients who needed to use painkillers (39%) used acetaminophen. Conclusions: Women and patients with heart rate ≥ 120 bpm before PACI should probably be considered for systematic painkillers after the implantation.

Aim: We aimed to identify a cutoff value of tumor size (TuS) correlated to prognosis of stage II and III colorectal cancer and to evaluate the prognostic significance. Patients & methods: We retrospectively analyzed 257 patients treated for stage II–III colorectal cancer between 2003 and 2014. We used receiver-operating characteristic to evaluate TuS performance accuracy to predict survival. We identified a cutoff value. We used the Kaplan–Meier method and Cox regression analysis to study survival and prognostic factors. Results: Area under the receiver-operating characteristic curve of TuS was 0.62 ± 0.048. A size of 4 cm was identified as a predictor of survival with a sensitivity of 88.2% and a specificity of 59.2%. We observed 98 patients with TuS ≤4 cm and 159 patients with TuS greater than 4 cm. Patients with TuS greater than 4 cm were more likely to have a cancer located in the colon (81.1 vs 70.4%, p = 0.002) and commonly pT4 (44 vs 22.4%, p = 0.0001). There was no difference in terms of gender, insufficient removed lymph nodes number, number of positive lymph nodes, stage and oxaliplatin administration between both groups. 5-year survival rate of patients with TuS ≥4 cm and TuS less than 4 cm was 76 and 84%, respectively (p = 0.008). Age ≥65 years, stage III, venous invasion and pN+ greater than 3 were significant bad prognostic factors in patients with TuS ≥4 cm in univariate analysis. Stage III was the only independent prognostic factor in multivariate analysis. Administration of chemotherapy was the only factor with significant impact on survival in univariate and multivariate analyses in patients with TuS less than 4 cm. Conclusion: TuS had not only an impact on survival but also interfered with other prognostic factors.

International audience; PURPOSE: This report compares the risk factors, the tumor phenotypes, and the BRCA1/BRCA2 genotype of early onset breast cancer (EOBC) patients between Southern Europe and North Africa. METHODS: Four hundred and fifty six women with invasive EOBC (

A new case of epithelioid hemangioendothelioma is reported to have occurred to a 67-year-old patient who consulted for right-sided chest pain. The work-up showed multiple right pulmonary lesions associated with bilateral moderate pleural effusion and left-sided pleural thickening and three hypodense nodules in the right lobe of the liver, peritoneal thickening, ascites, and multiple vertebral lytic lesions. The diagnosis of an epithelioid hemangioendothelioma was concluded through a histological examination of a computed tomography scan guided biopsy of the liver. The patient received a primary mono-chemotherapy with Adriamycin (75 mg/m2 every three weeks) and intravenous bisphosphonates without response and general status impairment. The patient died after 16 months of follow-up.

Summary Introduction We aimed to explore the use of complementary and alternative medicine (CAM) and to identify their side effects, when used in cancer patients. We also assessed the communication of the patients and families with the oncologist about this issue. Methods A cross-sectional survey of 120 adult patients treated for cancer in our medical oncology department between January and April 2019, using an anonymous questionnaire to assess complementary and alternative medicine use. Results One hundred twenty patients participated in the survey, among them 102 used CAM (85%). A majority of users were female patients (n = 72, 70.6%), and mean age was 52.4 years ± 11.6. Patients had breast cancer in 48% of cases. Wild herbs were the most commonly used alternative therapy (67.7%), particularly Ephedra foeminea (Alanda) in 52% of cases. Patients’ families incited them to use CAM in 64.7% of cases. Internet and social network (Facebook) were the major sources of information on CAM (79.4%), followed by family and friends (72.5%). Fourteen patients (13.7%) reported nausea and vomiting secondary to CAM use. We reported disruption of liver function in 9.8% of cases, and renal failure in 1.96%, with fatal issue in one patient using Ephedra. Nineteen patients (18.6%) informed their oncologist about the alternative therapy they received. Conclusion The oncologist has to explore the use of alternative therapies with their patients. Communication about CAM should be a part of cancer care. It may protect patients from some dangerous side effects and improve efficacy of conventional therapy.

We investigated human leukocyte antigen (HLA) profiles for Tunisians with nasopharyngeal carcinoma (NPC), their families, and a sample of unrelated healthy Tunisians in order to identify HLA specificities associated with familial NPC. HLA-A, -B, and -DRB1 typing was successful for 36 NPC patients, 72 unaffected family members, and 130 community controls, and the chi square or Fisher exact test was used to compare allele frequencies between cases and controls. We observed a consistent protective effect of HLA-DRB1*10 on NPC development. However, none of the NPC patients or their family members had a positive result for this HLA marker (0% vs 9.2% in controls, P = 0.047). In addition, HLA-A*26 was probably an induction marker, as its allelic frequency was significantly higher among NPC patients than among controls (P = 0.003) and among NPC patients than among at-risk family members (P = 0.067). Logistic regression analysis of the joint effect of selected HLA specificities showed that HLA-A*26 and HLA-A*30 were co-associated and have an important effect on NPC risk. Despite the small size of our cohort, we showed that HLA-A*26-A*30 and HLA-DRB1*10 might be predictive markers for NPC screening of Tunisian families with a high risk of NPC.

// Maroua Manai 1, 5, 6, 7 , Jeanne Thomassin-Piana 2, * , Amor Gamoudi 6, * , Pascal Finetti 1, * , Marc Lopez 1 , Radhia Eghozzi 6 , Sinda Ayadi 6 , Olfa Ben Lamine 6 , Mohamed Manai 5 , Khaled Rahal 6 , Emmanuelle Charafe-Jauffret 2, 3 , Jocelyne Jacquemier 2 , Patrice Viens 3, 4 , Daniel Birnbaum 1 , Hamouda Boussen 5, 7 , Max Chaffanet 1 , Francois Bertucci 1, 3, 4 1 Departement d’Oncologie Moleculaire, Centre de Recherche en Cancerologie de Marseille, Aix Marseille Universite, Marseille, France 2 Departement de Bio-Pathologie, Institut Paoli-Calmettes, Marseille, France 3 UFR de Medecine, Aix Marseille Universite, Marseille, France 4 Departement d’Oncologie Medicale, Institut Paoli-Calmettes, Marseille, France 5 Departement de Biologie, Unite de Biochimie et Biologie Moleculaire, Faculte des Sciences de Tunis, Universite de Tunis El Manar, Tunisie 6 Departement d’Oncologie Medicale, Institut Salah Azaiez, Tunis, Tunisie 7 Service d’Oncologie Medicale, Hopital l’Ariana, Tunis, Tunisie * These authors contributed equally to second authors Correspondence to: Francois Bertucci, email: bertuccif@ipc.unicancer.fr Keywords: expression, immunohistochemistry, inflammatory breast cancer, MARCKS, survival Received: July 29, 2016 Accepted: December 14, 2016 Published: December 21, 2016 ABSTRACT Background: Inflammatory breast cancer (IBC) is the most aggressive form of locally-advanced breast cancer. Identification of new therapeutic targets is crucial. We previously reported MARCKS mRNA overexpression in IBC in the largest transcriptomics study reported to date. Here, we compared MARCKS protein expression in IBC and non-IBC samples, and searched for correlations between protein expression and clinicopathological features. Results: Tumor samples showed heterogeneity with respect to MARCKS staining: 18% were scored as MARCKS-positive (stained cells ≥ 1%) and 82% as MARCKS-negative. MARCKS expression was more frequent in IBC (36%) than in non-IBC (11%; p = 1.4E−09), independently from molecular subtypes and other clinicopathological variables. We found a positive correlation between protein and mRNA expression in the 148/502 samples previously analyzed for MARCKS mRNA expression. MARCKS protein expression was associated with other poor-prognosis features in the whole series of samples such as clinical axillary lymph node or metastatic extension, high pathological grade, ER-negativity, PR-negativity, HER2-positivity, and triple-negative and HER2+ statutes. In IBC, MARCKS expression was the sole tested variable associated with poor MFS. Materials and Methods: We retrospectively analyzed MARCKS protein expression by immunohistochemistry in 502 tumors, including 133 IBC and 369 non-IBC, from Tunisian and French patients. All samples were pre-therapeutic clinical samples. We searched for correlations between MARCKS expression and clinicopathological features including the IBC versus non-IBC phenotype and metastasis-free survival (MFS). Conclusions: MARCKS overexpression might in part explain the poor prognosis of IBC. As an oncogene associated with poor MFS, MARCKS might represent a new potential therapeutic target in IBC.

Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. Methods A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. Conclusions In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific. Electronic supplementary material The online version of this article (10.1186/s12967-018-1504-9) contains supplementary material, which is available to authorized users.

The aim of this study was to investigate the association between serum concentrations of a group of organochlorine pesticides/polychlorinated biphenyls with xenoestrogenic potential and the risk of breast cancer in a female population from Tunisia. The relationship between serum levels of the pollutants and the risk of cancer was assessed using logistic regression analyses. In the unadjusted models, β-hexachlorocyclohexane (β-HCH), hexachlorobenzene, heptachlor, polychlorinated biphenyl congeners 138, 153, and 180, and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were positively associated with breast cancer risk. However, when the models were further adjusted for the selected covariates, only β-HCH and p,p'-DDE remained statistically significant, and heptachlor was borderline significant. In addition, analyses using POP concentration tertiles corroborated a positive dose-response relationship that was significant for p,p'-DDE (p-trend=0.020) and borderline significant for heptachlor (p-trend=0.078). A similar trend was also confirmed for β-HCH, in which concentrations≥limit of detection were positively associated with breast cancer risk (vs. concentrationslimit of detection, OR=3.44, p0.05). Finally, the relative influence of each chemical in the presence of the others was assessed by entering the three chemicals in a single model with all covariates, and only β-HCH remained positively associated with the risk of cancer (OR:1.18, 95%CI: 1.05-1.34). Our findings suggest a potential association between exposure to at least one organochlorine pesticide and breast cancer risk. However, our results should be interpreted with caution, and further research is warranted to confirm these findings.

Background: Small cell lung cancer (SCLC) accounts for 20% of lung cancers with aggressive presentation. Therapies for SCLC have lagged behind the current standard treatment, the prevailing state-of-the-art from the early 1980s. The aim of this study is to report the epidemiological, clinical profile, therapeutic protocols, and results of SCLC in Tunisian population. Methods: This is a retrospective study, including 60 patients treated for histologically diagnosed with SCLC between 2011 and 2015. Only patients with eastern cooperative oncology group (ECOG) performance status 0 to 2 were considered. Results: Sixty patients were enrolled in this study. The mean age was 61.8 years (range 45 - 77 years). Fifty-five (95%) patients were active smokers. The most frequent symptoms were cough, chest pain, and dyspnea. SCLC was staged as extensive disease in 40 patients (66.7%) and limited disease in 20 cases (33.3%). For diffuse stages, chemotherapy was possible in 34 (85 %) of patients. We observed 2 (5%) complete responses, 9 (22.5%) partial responses, 3 (7.5%) stable diseases, and 9 (22.5%) progressions. Only 11 patients (27.5%) received second line chemotherapy with a median time to progression of 2.2 months. Five patients died, 1 had partial response, and 3 had progressive disease. One patient received third line chemotherapy. For localized stages, 7 (35%) patients received concomitant radiochemotherapy, 5 (25%) primary chemotherapy followed by concomitant radiochemotherapy, and 8 (40%) sequential treatment. Two (10%) patients had complete response, 8 (40%) partial response, 3 (15%) stable disease, 4 (20%) progressive disease, and 1 patient died. Twelve patients relapsed (60%) with a median time to progression of 2 months. Ten patients received relapse chemotherapy. Four patients died from their disease and 4 had a progressive disease. The median survival was 10 months for the overall population, 12.5 months, and 9 months for localized stages and diffuse stages, respectively. Conclusions: In diffuse SCLC and even with ECOG performance status 0 to 2, first line chemotherapy was feasible in only 85% of cases and second line in only 27.5%. In localized disease, upfront therapy and relapse therapy were possible for 100% and 83% of cases, respectively.

Molecular profile of lung cancer is well known in developed countries. These countries reached the era of liquid biopsies, immunotherapy, and urine circulating tumor DNA. The discrepancies between developed countries and developing ones are becoming deeper. Because of a lack of data in Tunisia, we tried to analyze the molecular profile of non-small-cell carcinomas and to assess the morphologic subtype of adenocarcinomas according to their mutational profile.We performed molecular analyses in Tunisia and in France of 84 patients who were able to afford the cost of the diagnostic techniques carcinomas diagnosed between 2012 and 2015. The diagnosis was established in our Department of Pathology and the percentage of the tumor cells was estimated by the pathologists. The paraffin-embedded blocks were sent to France, in 41 cases and were analyzed in Tunisia in 43 cases. A next-generation sequencing was performed in France and a real-time polymerase chain reaction (PCR) was performed in our country.During the period of study, 1122 lung cancers were diagnosed and 87 patients were able to afford the molecular analyses cost. The mean age of these patients was 53 years. The sex ratio reached 1.9. The molecular analyses were not performed in three cases because of a low tumor cell rate. EGFR mutations were present in 16 cases: 3 men and 13 women. The adenocarcinomas were classified as acinar in 11 cases and solid in 5 cases. ALK-EML4 translocation was present in six cases. Mutations of BRAF, KRAS, P53, and ERBB4 genes were, respectively, detected in two cases, five cases (3 codon 12), three cases, and one case.This study made us wonder about the possibility of implementing molecular techniques in low-income countries and about the necessity of optimizing the financial resources.

Table S1 Breast cancer loci and variants investigated in the Tunisian population. Table S2 Data sources for in silico analyses of variants with high RegulomeDB scores. Table S3 Allelic frequency of the selected breast cancer polymorphisms and comparison of these frequencies between Tunisian and HapMap populations (Pairwise pvaluesâ

Figure S1 GTEX Boxplots representing the most significant eQTL results for variant rs9911630 in breast mammary tissue. Box plots represent the expression levels of the indicated transcripts with respect to the rs9911630 genotypes. Expression levels are shown for (a) NBR2 gene, (b) CTD-3199â J23.6 gene and (c) LINC00910 gene. Horizontal bars indicate mean expression level per genotype. Additional information on the eQTL p values are reported in Table 1. Figure S2 Alignment of the sequence around rs9911630 with binding site of (a) bmo-miR-3287, (b) ssa-miR-19d-5p and (c) mse-miR-2766. The SNP is shown in red and the allele binding the microRNA is also shown. Figure S3 Contributions of variables (SNPs and populations) in Dim1 and Dim2. The contribution of each tested variable (based on their variants frequencies) in the general variability between the different selected populations shown on the PCA (a) to the first dimension of the PCA (Dim1 for the variability between African and non-African populations â see Fig. 3) and (b) to the second dimension of the PCA (Dim2 for the variability between European and non-European populations). Figure S4 Contributions of each tested population in the general variability between the different selected populations shown on the PCA (a) the first dimension of the PCA (Dim1) and (b) the second dimension of the PCA (Dim2). Figure S5 A map of the linkage disequilibrium in intron 2 of FGFR2 gene containing two SNPs associated with breast cancer risk in the Tunisian population (rs1219648 and rs2981582). (DOCX 263 kb)

Additional file 2: Figure S1. Biological networks and Enriched gene ontology pathways identified by the functional annotation analysis. Enrichment network of the shared candidate disease genes and their upstream regulator based on biological processes using ClueGO Cytoscape plugin. Hyper-geometric (right-handed) enrichment distribution tests, with a p-value significance level of â ¤ 0.05, followed by the Bonferroni adjustment for the terms and leading term groups were selected based on the highest significance. The node size and deeper color indicates greater significance of the enrichment.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) polymorphism in Tunisian breast cancer patients. MMP-2 genotypes were determined by real-time polymerase chain reaction (RT-PCR), and TIMP-2 genotypes were identified using a PCR-restriction fragment length polymorphism (RFLP) method in 210 breast cancer patients and 250 frequency-matched control women. Association of the clinicopathological parameters and the genetic markers with risk of breast cancer was assessed using univariate analyses. We found that the variant MMP-2 genotype (-1306CT or TT) was associated with substantially reduced risk of breast cancer [odds ratio (OR), 0.49; 95 % confidence interval (95 % CI), 0.033-0.73], compared with the CC genotype. For TIMP-2, a moderately reduced risk of the cancer (OR, 0.57; 95 % CI, 0.37-0.87) was also associated with the variant allele (-418GC or CC), compared with the GG common allele. Furthermore, polymorphisms in both genes seem to have additive effects and the highest risk for breast cancer has been observed in those with MMP-2 CC genotype and TIMP-2 GC or CC genotype (p = 0.006). A significant association was also found between the CC genotype and the aggressive forms of breast cancer as defined by advanced stages at the time of diagnosis and metastasis. This is the first report on the association of MMP-2 and TIMP-2 gene polymorphisms in breast cancer in Tunisian population. Our results suggest that the presence of the variant allele in the promoter of MMP-2 or TIMP-2 may be a protective factor for the development of breast cancer.

Resume Objectifs Evaluer les donnees recentes de la litterature concernant les indications therapeutiques dans les cancers du rein localement avances et/ou metastatiques et analyser le benefice des therapies ciblees depuis leur adjonction dans l’arsenal de traitement. Methode Nous avons effectue une revue de la litterature en utilisant les mots-cles suivants, Renal Cell Carcinoma, Target Therapy, Surgery, Metastases, RECIST sur le moteur de recherche Pubmed pour rechercher des articles indexes entre les annees 1999 et 2014. Nous avons retenu les donnees des grandes etudes cliniques des differentes therapies ciblees dont nous avons fait la synthese et rapportons les recommandations actuelles d’utilisation pratique dans les cancers du rein a cellules claires (CRCC) localement avances et/ou metastatiques (LA/M). Resultats Les essais randomises recents de grande taille ont demontre l’efficacite des differentes therapies ciblees dans la prise en charge des CRCC en termes de survie sans progression. Conclusion L’unification et pratiquement « mondialisation » des protocoles doit beaucoup aux propositions therapeutiques, issues des resultats des differentes essais prospectifs et basees sur un niveau d’evidence eleve.

Personalized medicine is the result of the research made on the field of molecular biology. Lung cancer was mainly concerned with the establishment of many oncogenic drivers. Nowadays, the pathologist is facing a dilemma because of the multiplicity of therapeutic targets and molecular ones and the small size of specimen performed. In fact, 75% of lung cancer are diagnosed on biopsic samples. According to the recommendations of the 2013 International Group Study of Lung Cancer (IASLC), sequential analyses of Epidermal growth factor (EGFR) and anaplastic lym- phoma kinase (ALK) are necessary on adenocarcinomas, non small cell carcinomas not otherwise specified and non small cell carcinomas favor adenocarcinomas. Many interrogations are reported concerning the cost effectiveness of the diagnostic techniques and the targeted treatments. We wondered about the further feasibility of such a technique in a low income country by trying to explore the representativity of the samples. In our hospital, bronchoscopic biopsies are diagnostic in 75% of the cases. We receive a mean of 4 samples. 68% of the samples are tumoral. Immuno-histochemistry is performed in 68% of the cases with a mean of 2 antibodies used and 8% of the biopsies are non interpretable because of the small size of specimen. Concerning transthoracic biopsies, 20% are non contributive because of necrosis or the small size. We receive a mean of 1 sample with a mean size of 6 millimeters. Immunohistochemistry is performed in 71% of the cases with the mean of 2 antibodies. In addition to the scientific, pharmacoeconomic and ethic problems induced by targeted therapies in low income countries, each institution should optimize the use of the specimen received and the technical conditions in order to be ready to answer to the IASLC recommendation.

PURPOSE We evaluated the relation between first site of recurrence of early breast cancer and disease profile at presentation and reported survival results, suggesting a personalized diagnostic imaging guidance during follow up. METHODS Among 1400 early breast cancer treated from 2000 to 2010, 324 relapses were divided into 4 groups according to first site: A-locoregional, B-bone, C-Brain and D-visceral. We analyzed redictive factors of each group compared to a control group of 100 non relapsing patients and the remaining groups matched. RESULTS In group A, patients were more likely to have histological tumor size above >2 cm, grade 1-2, HR positive and 0-3 involved lymph nodes. In group B, patients had more commonly grade 2-3, 1-3 positive lymph nodes and HR positive tumors. In group C, patients were more frequently young, with large tumor size, grade3, positive lymph nodes and HER2 positive tumors. In group D, patients were more likely to have tumors>2 cm in size, with nodal involvement, grade 3, HR negative and HER2 positive tumors. Annual recurrence rate in group A, was stable ranging between 15%-18%, within the first 3 years and peaked at 19.4% in the interval [1-2]year in group B. Median survival was 46 months in group A, 43 months in group B, with no significant difference. CONCLUSION Outcome of loco-regional and bone relapses was good, suggesting that both systematic mammography and bone-scan/CT scan for high risk patients (N+, gradeIII) during the first 2-3 years may represent a tailored relevant follow-up protocol for breast cancer patients.

To report the annual hazard of relapse in stages II and III colorectal cancer (CRC) Tunisian patients treated with curative intent. We also aim to evaluate impact of oxaliplatine according to anatomo-clinical features. We collected data about clinico-pathological parameters of 331 CRCs. We analyzed annual hazard of recurrence (locoregional and/or distant) of the overall population and several subgroups: colon cancer vs rectal cancer and stage II vs stage III. We also analyzed impact of adjuvant oxaliplatine on recurrence within these subgroups. Relapse rate was 38.1%, with a mean time to relapse of 27.6 months. We noted 23.8% local recurrence, 69.8% distant recurrence, and 6.4% both. We observed higher local relapse rate in rectal cancer (26.8 vs 3.2%) vs colon cancer (p = 0.004). Stage III had a higher metastatic relapse rate vs stage II (31.6 vs 20.8%, p = 0.043). Annual hazard of recurrence for the overall population showed two peaks: [1–2] year-interval by 10.1% and [3–4] year-interval by 11.3%. Stage III showed significantly higher and earlier recurrence hazard peak compared to stage II (16.3 vs 8.1% in [1–2] year-interval). Oxaliplatine significantly improved annual hazard of recurrence in each year-interval from year 1–4, in colon cancer and in stage III but without impact in rectal cancer and stage II. Extended follow-up to 4 years should be considered in Tunisian population. Impact of oxaliplatine showed same features to reported occidental series.

Background NA chemotherapy (CT) +/- anti-Her2 treatment of operable breast cancer (BC) is considered a standard option in the management of BC. However, pathologic complete response (pCR) rates with CT in HR+/Her2- BC are usually low: 7% (Luminal A) to 16% (Luminal B). Alternatively, NA endocrine therapy (ET) has not been established as a standard treatment because of low pCRs. Methods This is a multicenter phase III, 3rd generation NA trial performed in 34 centers and 7 countries of Middle-East and North Africa (MENA Region). The objective is to investigate the potential role of adding Palbociclib to ET (Fulvestrant +/- Goserelin) compared to ET alone as NA therapy of HR+/Her2- operable BC sensitive to ET. The primary endpoint is pCR with the hypothesis that the addition of Palbociclib would increase the pCR rate from 5% to 15%. Clinical/radiological response, conservative surgery rate, safety, disease-free and OS are secondary endpoints. Exploratory endpoints encompass biomarker serial analysis of liquid biopsies with Quantum Optic and DNA methylation technologies. Results A total of 400 pre and post-menopausal pts with stage II and IIIA are planned to be recruited. Oncotype DX is performed upfront in order to eliminate CT candidates. All pts with a recurrence score (RS) Conclusions SAFIA trial aims to evaluate whether or not the addition of a CDK 4/6 inhibitor to pts sensitive to ET would validate a neo-adjuvant strategy without CT in luminal operable BC. Clinical trial identification NCT03447132. Legal entity responsible for the study International Cancer Research Group (ICRG). Funding Pfizer, AstraZeneca and Genomic Health. Disclosure All authors have declared no conflicts of interest.

Aim: Surgical treatment of hepatic or pulmonary metastases is the optimal therapeutic goal in metastatic colorectal cancer (CRC). Methods: Our retrospective study concerned 70 patients treated for CRC, collected from 2003 to 2015, presenting liver metastases (LM) in 61 cases and pulmonary metastases (PM) in nine cases, treated by surgery for their distant disease. We collected and compared their epidemiologic, anatomoclinical parameters and analyzed several prognostic factors. Results: Metastases were multiple (≥ 4) in 9/61 LM and in 5/9 PM. Patients had synchronous metastases in 32 cases (30 LM/2 PM) and metachronous metastases in 33 cases (32 LM and 11 PM). Surgery for LM consisted of metastasectomy (49/61), segmentectomy (5/61) and hepatectomy for the remaining seven patients; ten patients had also subsequent liver radiofrequency. LM were treated by wedge resection in 6/9 and lobectomy in two cases, radiofrequency was performed in five cases. 56/61 (80%) patients received chemotherapy, mostly FOLFOX protocol as the first-line treatment and targeted therapy in 55% of cases. For the overall population, median OS and PFS were, respectively, 44 and 32 months. We did not observe any significant difference in terms of OS (p = 0.659) and PFS (p = 0.318) between resected LM or/and PM. A better survival was found when there was disease-free interval between the occurrence of the primary and the metastases exceeded 18 months and in patients with less than four metastases. Conclusion: Resection of metastatic disease mostly in liver and lungs improves survival of patients with CRC. The patients with longer disease-free interval and less than four metastases had the best outcomes.

The use of regimens with adjuvant taxanes reduces the risk of recurrence and improves survival in patients with node-positive breast cancer, but the use of taxanes in node-negative breast cancer is still to be defined. The aim of this study is to evaluate the role of taxanes in high-risk node-negative breast cancer. Two categories of studies were reviewed: studies that evaluated both node-positive and node-negative breast cancers, and studies that included only high-risk node-negative breast cancers. Three phase-III studies that evaluated both negative and positive nodes did not show any benefit of the use of taxanes according to the node-negative subgroup analyses, versus two studies (European Cooperative Trial in Operable Breast Cancer [ECTO] et Grupo Espanol de Investigacion del Cancer de Mama [GEICAM]) that showed a significant difference in disease-free survival. In view of these studies, the role of taxanes in node-negative breast cancer is still controversial and the results of the ongoing trials may respond to this subject.

Xeroderma Pigmentosum(XP) is a rare recessive autosomal cancer prone disease, characterized by UV hypersensitivity and early appearance of cutaneous and ocular malignancies. We investigated four unrelated patients suspected to be XP-C. To confirm linkage toXPCgene, genotyping and direct sequencing ofXPCgene were performed. Pathogenic effect of novel mutations was confirmed by reverse Transciptase PCR. Mutation screening revealed the presence of two novel mutations g.18246G>A and g.18810G>T in theXPCgene (NG_011763.1). The first is present in one patient XP50NEF, but the second is present in three unrelated patients (XP16KEB, XP28SFA, and XP45GB). These 3 patients are from three different cities of Southern Tunisia and bear the same haplotype, suggesting a founder effect. Reverse Transciptase PCR revealed the absence of theXPCmRNA. In Tunisia, as observed in an other severe genodermatosis, the mutational spectrum of XP-C group seems to be homogeneous with some clusters of heterogeneity that should be taken into account to improve molecular diagnosis of this disease.

Matrix metalloproteinase-2 (gelatinase A) is a well-known mediator of cancer metastasis, but it is also thought to be involved in several aspects of cancer development, including cell growth and inflammation. In the present study, we investigate whether MMP-2 SNP, MMP-2 mRNAs, and MMP-2 protein are associated with the susceptibility to colorectal cancer in the Tunisian population. The TaqMan allele discrimination assay and DNA sequencing techniques were used for genotyping; MMP-2 expression of each genotype was analyzed by semiquantitative RT-PCR, and MMP-2 protein expression was analyzed by immunohistochemistry staining. Our result showed that the levels of MMP-2 mRNA expression in patients containing the CC genotype were much higher compared with cells with the CT genotype. The frequency of the MMP-2 CC genotype was significantly higher in colorectal cancer patients when compared with controls (OR=1.94; 95% CI, 1.117-3.680). A higher intensity of staining of MMP-2 was observed in regions of invasion of the muscularis mucosa compared with superficial portions of the tumor. In addition, we found a significant progressive increase in total MMP-2 plasma levels with progression from adenomatous polyps through advancing Dukes stages (P=0.0001). Our data suggest that MMP-2 may be associated with colorectal cancer development and invasion in the Tunisian population; moreover, SNP and levels of MMP-2 could be a predictive value for colorectal cancer prevention and invasiveness.

Human epidermal growth factor receptor-2 (HER2) is amplified in 25-30% of breast cancers and is associated with aggressive disease and poorer survival. Multiple anti-HER2 targeted therapies have dramatically changed management and outcome of this subgroup, both in adjuvant and metastatic settings. Despite the improvement of survival thanks to trastuzumab, unclear mechanisms of resistance occur, which has led to the development of new anti-HER2 therapies such as lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1). The optimal sequence of the available drugs is still not well established. All this progress raises the question of toxicity that need to be managed, especially with longer survival of patients. In this article, we review different anti-HER2 therapies used in HER2-positive m etastatic breast cancer.

International audience; Tissue inhibitors of metalloproteinases (TIMPs) appear to affect many aspects of cancer biology, playing a crucial role in cell signaling by regulating cell growth, apoptosis, invasion, metastasis, angiogenesis, and genomic instability. In the present study, we investigate whether TIMP-2 SNP, TIMP-2 mRNAs, and TIMP-2 protein is associated with susceptibility to colorectal cancer (CRC) in Tunisian population. Taqman and DNA sequencing techniques were used for genotyping, TIMP-2 expression of each genotype was analyzed using semiquantitative RT-PCR and TIMP-2 protein expression was analyzed using immunohistochemistry staining. Our results showed that significantly elevated CRC risk was found in individuals with CC genotype (odds ratio 1.959; 95% confidence interval, 1.055-3.637). Moreover TIMP-2 mRNA expression in the colorectal cell carcinomas was significantly higher compared with the normal colorectal tissue (0.487±0.015 vs. 0.210±0.013) (P

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.

Aim The objective is to report the correlation between pathology and molecular subtype classifications of breast cancer in Tunisian women. Methods This retrospective study concerned data of 966 breast cancer cases collected from 2007 to 2009 at Salah Azaiz Institute of Tunis. These cases were classified by an immunohistochemistry test for estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2) status in the four molecular subtypes, namely luminal A, luminal B, HER2+ and triple negative. The molecular classifications were correlated with the clinicopathological characteristics of the tumors. Results Luminal A (50.7% of cases) was the most common subtype, with triple negative subtype 22.5%, luminal B 13.4% and HER2+ 13.4%. Triple negative and HER2+ subtypes were significantly associated with large tumor size (>5 cm, P

Targeted therapies (TT) represent since 10 years, an interesting progress in oncology for many cancers in adjuvant, neoadjuvant or palliative situation. The development of this new class of drugs, with an original mechanism of action, their easy administration, mainly per os, and a particular toxicity profile different from "classical" chemotherapy (CT) leads them entering in the therapeutic arsenal of breast, digestive tract, lung and hematologic cancers, in association with CT. Medical oncologists took rapidly the train of TT, managing a new and original skin, digestive, cardiovascular, endocrine and pulmonary toxicity profile, that remains relatively less important than "classical" CT.

Resume Introduction Le lymphome primitif du grele (LPG) est le deuxieme lymphome malin non hodgkinien (LMNH) digestif apres celui de l’estomac. Objectif Evaluer l’evolution epidemiologique, anatomoclinique et therapeutique des LPG en Tunisie sur une experience acquise durant plus d’un quart de siecle. Patients et methodes Notre etude retrospective a collige les patients, chez qui le diagnostic de LPG a ete prouve histologiquement entre 1981 et 2008, inclus a l’institut Salah Azaiz. La cohorte de 210 patients a ete divisee en deux groupes : le premier groupe de 152 patients traites de 1981 a 1992 (A) et le second (B) de 58 cas traites de 1993 a 2008. Nous avons etudie les donnees epidemiologiques, anatomocliniques, histologiques et les resultats therapeutiques. Resultats Outre la baisse de l’incidence annuelle des LPG, nous avons observe une nette transition, d’une predominance des lymphomes de type immunoproliferative small intestinal disease (IPSID) encore appeles « Mediterraneen » diffus du grele vers une frequence relative plus importante des formes « occidentales ». La chirurgie exploratrice et/ou de reduction tumorale, largement pratiquee dans le groupe A, a disparu au profit de la chimiotherapie premiere ( p Conclusion Les LPG en Tunisie ont subi une triple transition : epidemiologique, histologique et therapeutique.

Because nasopharyngeal carcinoma (NPC) has a close association with Epstein-Barr virus (EBV), measuring serum EBV DNA and anti-EBV serum marker concentrations could be a feasible method for NPC diagnosis, monitoring and probably screening especially in a community at risk. The aim of this study was to determine the EBV pattern in sporadic NPC and in high risk NPC Tunisian families in order to evaluate their risk factors and help for NPC screening. The rates of anti-EBV antibodies and EBV DNA were determined in the serum of 47 healthy members randomly selected from 23 NPC multiplex families with two or more affected members, 93 healthy Tunisian community controls chosen with the same age, sex and geographic origin as unaffected individuals and 66 EBV positive sporadic NPC patients whose serum was available before and after treatment. Unexpectedly, significant lower concentrations of anti-EA (Early Antigen) IgG and anti-VCA (Viral Capsid Antigen) IgG were found in unaffected members from NPC families than in healthy controls while viral loads were negative in all the tested sera. For sporadic NPC patients, anti-EA IgG and anti-VCA IgA concentrations were significantly higher than in healthy controls and these rates decreased after treatment. The level of EBV DNA load varied according to the condition of the tumour. This study suggests that in the Tunisian NPC families, screening for malignancy is based on serum concentrations but not on EBV DNA load while in the sporadic NPC group, serologic markers and EBV DNA load are complementary for diagnosis and follow-up.

Resume Introduction Les angiosarcomes du sein sont des tumeurs vasculaires rares. Elles representent 0,4 % de l’ensemble des tumeurs malignes du sein et 3 a 9 % des sarcomes mammaires. Patients et methode Il s’agit d’une etude retrospective portant sur dix cas d’angiosarcome (neuf femmes et un homme) du sein colliges au service d’immuno-histocytologie de l’hopital Salah Azaiez sur une periode de 31 ans entre 1977 et 2007. Resultat La moyenne d’âge etait de 40 ans. Le mode de decouverte a ete un nodule du sein avec un etat general conserve dans tout les cas. La taille moyenne de la tumeur etait de 5,5 cm. La mammographie a revele une masse bien limitee dans cinq cas. Une mastectomie a ete pratiquee chez huit patients associee dans quatre cas a une radiotherapie et dans un cas a une chimiotherapie. Le traitement conservateur a ete indique dans deux cas. L’examen histologique a montre un aspect typique d’angiosarcome dans huit cas. La survie sans recidive allait de quatre mois a 13 ans. Deux patientes ont ete perdues de vue apres le diagnostic d’angiosarcome. Quatre de nos patients n’ont pas developpe de recidive locale ou de metastase a distance. Deux patientes ont developpe une recidive locale ou de metastase a distance. Deux patientes ont developpe une recidive locale apres huit et 18 mois. Une patiente a developpe une metastase osseuse apres 29 mois. Conclusion Les angiosarcomes du sein sont des tumeurs rares qui posent un probleme diagnostique differentiel avec les angiomes. En consequent, une surveillance rapprochee et reguliere s’impose pour les tumeurs vasculaires.

The original version of this article unfortunately contained a mistake. The given name and family name were swapped.

Due to the significant advances in the diagnosis and treatment of breast cancer seen in the last decades, increased survival rates and better outcomes of patients are being observed. The role of radiotherapy remains pivotal in the treatment of early breast cancer. In the adjuvant setting, whole breast irradiation remains the standard of care using a relatively well standardized radiation technique. The recent technology advances and 3D conformal radiotherapy allow for better volumes definition resulting to increased organ at risk--sparing and therefore treatment optimization. Sophisticated techniques and emerging options (such as accelerated partial breast irradiation) are not routinely used yet outside of a clinical trial. Moreover, new drugs and targeted therapies have recently been introduced to the clinical practice for treatment individualization according to the specific tumours' prognosis and/or prediction of the drugs' efficacy based on new biological tools. Regarding the synergistic effect of these molecules with ionizing radiation, rigorous prospective evaluation of combined therapy is important to ensure improved long-term benefit/risk ratio. In this review, the significant advances of radiotherapy and combined therapy in the new era of breast cancer management will be discussed.

Purpose We conducted a phase II, open-label, multicenter study to evaluate the efficacy, safety, and tolerability of daily lapatinib plus weekly paclitaxel in treatment-naïve patients with inflammatory breast cancer (IBC). Patients and Methods The primary end point was pathologic complete response (pCR). Secondary end points included combined clinical response rate (based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria and clinically evaluable skin disease criteria). Patients were assigned to either cohort A (human epidermal growth factor receptor 2 [HER2] 2+ or 3+ by immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH] –amplified ± epidermal growth factor receptor [EGFR] expression) or cohort B (HER2-negative/EGFR-positive). A subpopulation of cohort A considered HER2-positive by the current definition of overexpression (3+ by IHC or FISH-amplified) was also analyzed. Patients received lapatinib at 1,500 mg/d for 14 days, then lapatinib at 1,500 mg/d plus weekly paclitaxel (80 mg/m2) for 12 weeks, followed by surgical resection or additional chemotherapy. Results Forty-nine women were enrolled (cohort A, n = 42; cohort B, n = 7). Cohort B was terminated because of slow accrual and lack of efficacy observed in IBC patients with HER2-negative/EGFR-positive tumors enrolled onto the parallel study, EGF103009. pCR occurred in 18.2% (95% CI, 5.2% to 40.3%) of cohort A patients. Combined clinical response rate was 78.6% (95% CI, 63.2% to 89.7%) in all cohort A patients and 78.1% (95% CI, 60.0% to 90.7%) in the HER2-positive subset. Common adverse events included diarrhea, rash, alopecia, and nausea (> 50% of patients in both cohorts). The incidence of grade 3 diarrhea was 55%. Conclusion Lapatinib monotherapy for 14 days followed by lapatinib plus paclitaxel for 12 weeks provided clinical benefit in IBC patients with HER2-overexpressing tumors without unexpected toxicity.