Anticancer Center Research Articles

Coagulase negative staphylococci in Anti-Cancer Center, Batna, Algeria: antibiotic resistance pattern, biofilm formation, and detection of mecA and icaAD genes

Background : Coagulase-negative staphylococci (CoNS) are normal microbial flora found on the skin and mucous membranes of mammals. Considered for a long time as avirulent commensals, these bacteria are now recognized as opportunistic pathogens by virtue of their high resistance to multiple antibiotics and capacity for biofilm formations, which made them important agents of nosocomial and community-acquired infections. The objectives of this study are to determine the antibiotic resistance pattern and biofilm formation, and to detect mecA and icaAD genes in clinical CoNS isolates from Batna’s Anti-Cancer Center (ACC) in Algeria. Methods : A total of 66 CoNS were isolated from different samples and identified by API Staph system. In vitro antibiotic susceptibility testing (AST) of each isolate to selected antibiotics was determined by the disk diffusion method, and minimum inhibitory concentrations (MICs) of oxacillin and vancomycin were determined by E-test. Biofilm formation was assessed by Tissue Culture Plate (TCP) and Congo Red Agar (CRA) methods. The polymerase chain reaction (PCR) was used to amplify mecA gene in 9 oxacillin-resistant and 1 oxacillinsensitive CoNS, and icaAD gene in 9 biofilm forming and 1 non-biofilm forming CoNS. Sequencing of the 16S rDNA of 1 mecA and 1 icaAD positive isolates was performed by the Sanger method. Results : Nine species of CoNS were identified, with Staphylococcus epidermidis (n=29, 44%) and Staphylococcus haemolyticus (n=15, 22.7%) constituting the largest proportion, and isolated mainly from the onco-haematology service unit of the center. The isolates were resistant to penicillin G (98.5%), cefoxitin (80.3%) and oxacillin (72.2%). The TCP method was more sensitive (89.4%) than CRA method (31.8%) in detecting biofilm formation. The mecA gene was detected in 66.7% (6/9) of oxacillin resistant CoNS and the icaAD gene in 55.6% (5/9) of TCP positive CoNS isolates Conclusion : Invitro resistance to methicillin (oxacillin) and biofilm formation were high among the CoNS isolates in this study, but the association of these with respective carriage of mecA and icaAD genes was low. Keywords : Coagulase negative staphylococci, identification, antibiotic resistance, biofilm, PCR

1023P - Use of bevacizumab (Bev) in real life for first-line (fl) treatment of ovarian cancer (OC)/ The GINECO ENCOURAGE cohort of 500 French patients

BackgroundBevacizumab (bev) is approved in Europe (EU) for first line therapy of OC patients (pts). This study aimed to evaluate the use of Bev in real life, with a focus on toxicity. MethodsRepresentative centers in France of French regions and of mode of practice were asked to participate. From 04/13 to 02/15, among the consecutive OC pts treated in each center, were selected those who were newly diagnosed and planned to receive Bev. An independent CRA captured the clinical data at baseline, 6, 12, 18 and 36 months. ResultsA total of 104 centers participated: Private practice (44%), non-academic hospital (31%), academic (11%), anticancer center (14%). 1290 pts were screened, 500 registered and 468 were evaluable. Pts characteristics at baseline were: median age 65 yrs, antihypertensive therapy (26%), anticoagulant (10%), cardiac history (5%), serous histology (83%), interval surgery (47%), complete surgical debulking (74%) and carboplatin-paclitaxel chemotherapy (98%). Only 3.4% were not FIGO stage IIIB-IV. Pts received Bev at 15mg/kg (80%) during a median of 18 cycles (10-21) and 7.8% stopped treatment for toxicity. Main toxicity was HTA requiring new therapy (38%), PRES (1.3%), venous thrombosis (5%), proteinuria (9.8%) and nephrotic syndrome (2.6%). Other toxicities mostly reported include low grade epistaxis, gingivorrhagia, arthralgia, headache and dysphonia. Gastrointestinal perforation, fistula, arterial events and grade 3-4 bleeding were very low: 0.2%, 0.8%, 0,1% and 0.2% respectively. No pts developed congestive heart failure nor died from toxicity. Median PFS was 17.4 months (IC95% [16.4-19.1]) and % of pts alive at 3 years was 62.4% (IC95 % [58.1-67.1]). ConclusionsIn routine practice among French centers, first-line Bev administration is consistent with the EU label in most of the cases. Efficacy and safety in the real life were in line with that reported in trials excepted for a higher incidence of observed HTA and complications, suggesting the importance of increased education on HTA monitoring. Legal entity responsible for the studyARCAGY-GINECO. FundingRoche. DisclosureA. Floquet: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche. O. Tredan: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): BMS; Honoraria (self): MSD. J. Alexandre: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Novartis. C. Garnier Tixidre: Honoraria (self): Lilly; Honoraria (self): AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Pfizer. P. Follana: Advisory / Consultancy: Novartis; Advisory / Consultancy: AstraZeneca; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: AstraZeneca; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Tesaro. C. Levaché: Travel / Accommodation / Expenses: Sanofi. E. Pujade-Lauraine: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Tesaro. F. Selle: Honoraria (self): Roche; Honoraria (self): MSD France; Honoraria (self): PharmaMar; Honoraria (self): Tesaro; Honoraria (self): Clovis; Honoraria (self): AstraZeneca; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD France; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca. All other authors have declared no conflicts of interest.

Editorial introductions

Current Opinion in Oncology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of psychiatry is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Jean A. KlasterskyJean A. KlasterskyProfessor Klastersky was Head of the Department of Medicine at the Institut Jules Bordet in Brussels, Belgium, and Professor of Medicine, Medical Oncology and Physical Diagnosis at the Université Libre de Bruxelles, Belgium, from 1977. He retired from these positions in 2005. Currently, he is the coordinator of the “Programme des Soins Oncologiques” for the Public Hospitals in Brussels and consultant in medical oncology at the Institut Jules Bordet, Belgium. Professor Klastersky was an intern and resident at the University Hospitals of the Université Libre de Bruxelles between 1962 and 1965, where he gained his MD (Docteur en Médecine, Chirurgie et Accouchements). From 1967 to 1968, he was Chief-Resident at Boston City Hospital, USA, and then a Research Fellow and Assistant in Medicine at Thorndike Memorial Laboratory Harvard Medical School, USA. He became Chief of the Section of Infectious Diseases at the Institut Jules Bordet in 1970, before taking up the position of Head of the Department of Medicine in 1977. Professor Klastersky was a founder member of the European Lung Cancer Working Party and was President from 1978 until 2003. He was President (and founder member) of the International EORTC Antimicrobial Therapy Project Group between 1979 and 1987 and the Group's Secretary General from 1987 to 2000. He was President (and founder member) of the Multinational Association for Supportive Care in Cancer (MASCC) from 1990 to 2000. He has been Visiting Professor of Medical Oncology at the Charles University in Prague, Czech Republic, since 1994. Professor Klastersky is a member of the American Society of Clinical Oncology, the American Association of Cancer Research, the European Society of Medical Oncology, the American Society of Microbiology, the Infectious Diseases Society of America, the International Association for the Study of Lung Cancer, the “Royale Académie de Médecine” of Belgium and various other international and national medical and/or oncological societies. Professor Klastersky is the author of over 400 original articles, nearly 400 review articles and 17 scientific books. He is the Editor of Current Opinion in Oncology. Jean-Yves BlayJean-Yves BlayPr. Blay has published over 600 peer-reviewed articles. He was President of the European Organization for Research and Treatment of Cancer (EORTC) from 2009 to 2012. He has also received numerous awards such as the Hamilton Fairley Award in 2012 from the ESMO and the Henry and Mary-Jane Mitjavile prize in 2013 from the National Academy of Medicine. Currently President of the French Sarcoma Group GETO, he is the network leader of the NETSARC network of reference centers for sarcoma treatment certified by the French National Cancer Institute, the former PI of Conticanet (a FP6 network of excellence), and the current PI of the FP7 project EuroSARC). He is the Director of the Integrated Centre for innovation on Cancer Research of Lyon (LYRIC). He is the Network Director of the European Reference Network EURACAN (euracan.org). His research interests focus on clinical and basic research in sarcomas, targeted treatment of cancer, the biology of breast carcinoma and relation between tumor immunologic microenvironment and malignant cells with the goal of clinical applications in the fields of diagnosis, prognosis and treatment. Alain HendliszAlain HendliszDr Alain Hendlisz is a gastro-enterologist. He gained his MD (Docteur en Médecine, Chirurgie et Accouchements) at the Université Libre de Bruxelles, Belgium in 1988 and has been a specialist in gastroenterology since 1993. He earned his PhD in Medical Sciences at the ULB in 2015. He is currently Head of the Gastroenterology Unit at the Institut Jules Bordet, Anti-Cancer Center of the Université Libre de Bruxelles He is a founding member and is currently serving on the Board of the BGDO (Belgian Group for Digestive Oncology). He is a member of the American Society of Clinical Oncology (ASCO), the European Society of Medical Oncology (ESMO), the Société Royale Belge de Gastro-entérologie (SRBG) and European Organization for Research and Treatment of Cancer (EORTC). He is involved as principal investigator or co-investigator in numerous national and international clinical studies.

Proof-of-concept study evaluating a new tool for standardizing radiological assessment of tumor response to treatment in routine clinical practice.

e18079 Background: Internationally recognised criteria to evaluate tumour response, such as Response Evaluation Criteria In Solid Tumors (RECIST) and iRECIST (for immunotherapeutics) are not widely used in clinical practice. The main reason is that communications amongst health professionals are insufficiently standardised. To this purpose, ON’COHUB (MIRIO in France), a newly developed tool, automatically streamlines interactions between oncologists and radiologists to optimise and facilitate response evaluation according to the standard criteria. This study aims to identify the benefits in terms of user satisfaction and to provide preliminary data for the standardisation of the tool. Methods: Five oncologists, 3 radiologists, 1 clinical research associate and 1 clinical project officer used ON’COHUB to assess patients’ tumour responses according to RECIST, in an anti-cancer center, over five months. An oncologist compared patients’ regular radiology reports (n = 110) and ON’COHUB’s reports (n = 106), using the following report quality indicators: information on the patient’s context, target and non-target lesions , baseline, NADIR, and overall evaluation. Then a questionnaire on the user’s satisfaction was administered. Two-tailed chi-square tests were performed to compare patients’ regular radiology reports and ON’COHUB’s reports. Results: ON’COHUB was reported to significantly improve the following quality indicators compared to regular reports: presence of the treatment (99% vs 42%; p < 0,001), follow-up criteria (98% vs 5%; p < 0,001); target lesion and location (100% vs 75%; p < 0,001), size of target lesions (99% vs 67%; p < 0,001), value and date of the baseline (100% vs 0% and 4%, respectively; p < 0,001 for both), value of the baseline lesion by lesion (99% vs 4%; p < 0,001), value and date of the Nadir (97% vs 0%; p < 0,001), global response according to RECIST (100% vs 17%; p < 0,001), value of target lesions response (80% vs 20%; p < 0,001), referential for RECIST calculation (98% vs 2% p < 0,001).Finally, 9 out of the 10 users declared that they would use ON’COHUB on a daily basis. Conclusions: These preliminary data suggest that ON’COHUB may have a positive impact on the quality of the treatment response evaluation in clinical trials and in routine use. These results will be confirmed with the deployment of the interoperability with IT hospital System.

BRCA1 and BRCA2 Germline Mutation Analysis in Hereditary Breast/Ovarian Cancer Families from the Aures Region (Eastern Algeria): First Report.

Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. In this study, we aimed to investigate the mutation spectrum of BRCA1 and BRCA2 genes in hereditary breast/ovarian cancer (HBOC) families from the Aures region (eastern Algeria). High risk breast/ovarian cancer families were selected from overall 1162 consecutive patients collected from cancer registry of anticancer center of Batna. Breast cancers were diagnosed between 2011 and 2015. Recurrent mutations on BRCA1 and BRCA2 previously found in Algerian patients were screened using PCR-direct sequencing in 113 HBOC families. In addition, for the first time in Algeria, HBOC patients were analyzed by NGS using a cancer panel of 30 hereditary cancer genes or BRCA1/2 genetic test. Six distinct deleterious mutations in BRCA1 and BRCA2 and a new VUS in PALB2 were detected in ten patients. Two distinct BRCA2 pathogenic variants c.1813dupA and c.8485C > T detected in two young female triple negative breast cancer (TNBC) patients, respectively, with a family history of male breast cancer, are reported here for the first time in Algerian population. Interestingly, we also detected a BRCA exon 15 deletion in two unrelated young female TNBC patients with strong family history of breast/ovarian cancer. Our study showed differences in the distribution of the mutation spectrum of BRCA genes between the Aures region and the north central region of Algeria. Our results will contribute in the implementation of genetic counseling and testing for patients and families at risk of hereditary breast and ovarian cancer.

Real World Management of Patients with Acute Myeloid Leukemia: Results from French Cancer Population-Based Registries

Introduction:Cancer registries are required for the analysis of incidence and mortality rates and trends but are also useful as complement to clinical studies to support decision on individual patient management. Acute myeloid leukemia (AML) is more common in older people, with a continuous slow rise in young adulthood turning into rapidly increasing incidence by age from approximately 50 years. Clinical studies have criteria for inclusion and exclusion, which impose selection. This has less implication in younger patients because most of them receive intensive treatment, fewer have secondary AML, and few have severely impaired performance status. Many clinically relevant questions cannot be answered in randomized studies, because of limited patient numbers, problems with randomization, or resource availability.Population-based registries provide a way to achieve new information through the study of geographic differences. Healthcare authorities are interested in geographic variation to ensure equal level of health care for the citizens and the general population to know where to go for the best of care.The aim of this study was to describe the management and outcomes of adult AML patients diagnosed and reported to 3 different regional cancer population-based registries considered representative of the whole French population between years 2006 and 2012.Patients and methods:A total of 1106 patients were available in the 3 registries (446 in Gironde department, 472 in Basse-Normandie, and 188 in Côte d'Or department); 584 (53%) were males, age at diagnosis was comparable between the 3 departments with median of 66 years (range: 18-99), 431 (39%) were less than 65 years old and 437 (39%) were older than 75 years. Therapy-related AML was diagnosed in 126 (11%) patients, cytogenetic analysis was not homogeneously performed among the three departments, and also among those who had it done (N=815, 74%), 29% were normal, and from the remaining with abnormal cytogenetics, 69 (8%) were favorable prognosis, 121 (15%) intermediate, and 359 (44%) were unfavorable.Results:Two-third of patients (N=725, 66%) were followed in university hospitals, 7% in anti-cancer centers and the rest were followed in other hospitals. Among the total population, 915 (83%) were treated for their AML, most of them were <75 years old, and the rest of patients were not treated or received palliative care, only 67% of patients > 75 years were treated. There was no statistical difference in terms of overall survival (OS) between males and females (p=0.99). When stratifying according to age < 60, 60-65, 66-75 and > 75 years, OS probability at 5 years was 50% (95%CI: 44-56), 20% (95%CI: 12-27), 16% (95%CI: 11-21), 2% (95%CI: 1-4) respectively. OS was not different between the 3 departments. Information about inclusion in clinical trials was available for 50% of patients, among them 174 (19%) were included in clinical trials and 284 (31%) not. There was a clear significant survival advantage for patients included in clinical trial independently from age, p<0.001. OS was significantly better for patients treated in university hospitals and anti-cancer centers than those followed in other centers p<0.001. When evaluating the impact of period of treatment, survival outcome significantly improved during years 2010-2012 compared to years 2006-2009, p=0.04 only for patients aged less than 65 years, while patients older than 65 years did not have survival improvement over time, p=0.41. In addition patients who received allogeneic hematopoietic cells transplantation (allo-SCT) had a better OS, p=0.01. In multivariate analysis, age <65 years (HR=0.45, 95% CI: 0.38-0.54, p<0.001), favorable cytogenetics (HR=0.26, 95% CI: 0.15-0.45, p<0.001), unfavorable cytogenetics (HR=1.61, 95% CI: 1.32-1.97, p<0.001) and allo-SCT (HR=0.49, 95% CI: 0.38-0.64, p<0.001) significantly impacted OS.Conclusion:This analysis allowed to point out some disparities in the real world management of AML patients. Interestingly, the fact that survival outcome for patients treated in clinical trials is different from the rest of the population reflects an important point to consider by health authorities. In addition, we observed a lack of improvement over time for older patients that needs more attention. A prognostic evaluation is ongoing to verify patients deemed eligible for allo-SCT to find out among them the proportion of those really transplanted. DisclosuresTroussard:Gilead: Other: scientific advisory board. Michallet:Octapharma: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy; Novartis: Research Funding.

548P - Can we improve cost effectiveness of oncology clinical trials workflow? A prospective RECIST 1.1 study

Background: Oncology clinical trials require reliable imaging data management, however recurring nonconformity issues are commonly reported. Radiological workload is increasing, which reduces radiologist’s availability and potentially affects diagnostics quality. In this study, we compared performances of an institutional standard radiological workflow (SW) and a novel “hybrid workflow” (HW). Methods: We prospectively studied imaging data of 40 patients included in a RECIST 1.1 clinical trial (Apr-Dec, 2017) at Centre Antoine Lacassagne (CAL), Nice, France. 97 time-points were reviewed by 7 radiologists and one trained technologist. Nonconformities using the SW were retrieved from CALs’ 2015 archives. SW involved radiologists who used the Advantage Workstation platform without electronic reporting system (General Electric, USA). For the HW, radiologists performed all baseline evaluations and the technologist did the subsequent generic measures on follow ups. Radiologists then checked the technologist’s findings, before confirming the evaluations. The HW used LMS (Median Technologies, France) featuring an electronic reporting system. An independent body compared SW and HW reading time and nonconformity occurrences. Results: Using SW, 19 types of nonconformities were found: blank report (13%); unsigned report (11%); undocumented change of tumor burden (10%); undocumented new lesions (9%); missing/wrong patients’ visit date (7%); undocumented tumors location (5%); error in tumor burden change (5%). SW and HW nonconformities affected 55% (179/323) and 5% (2/40) of reports respectively (p < 0.001). HW nonconformities were: one wrong login name entered in the LMS platform and one erroneous time point numbering. SW required, on average, 11’30” [10’06”; 13’20”] to perform the radiological analysis per timepoint. HW required 1’35” [40”; 5’08”] for radiologists, and 12’18” [11’12”; 14’18”] for the technologist. Conclusions: HW significantly reduced the number of trial nonconformities and saved 87% of radiologists’ time while keeping their expertise in the final decisions. HW could represent an efficient cost reduction opportunity associated with imaging trial quality improvements. Legal entity responsible for the study: Antoine Lacassagne Anticancer Center. Funding: Has not received any funding. Disclosure: H. Beaumont, C. Klifa: Employee: Median Technologies. All other authors have declared no conflicts of interest.

Editorial introductions

Editorial introductions

Risk factors of cancer occurrence after surgery of oral intraepithelial neoplasia: A long-term retrospective study.

Oral intraepithelial neoplasia (OIN) is a premalignant lesion of oral mucosa graded I through III according to the importance of atypic cells and the thickness of the dysplastic layers. The aim of this study was to evaluate the long-term clinical course of OIN lesions and identify predictive factors of outcomes. The clinical, surgical, and follow-up data of the patients consecutively treated for OIN by primary surgical removal in a referral anti-cancer center from November 1998 to March 2009 were retrospectively analyzed. The main outcome parameters were the 10-year disease-free survival (DFS), cancer-free survival (CFS), overall survival (OS), and disease-specific survival (DSS) rates (Kaplan-Meier). Thirty-one patients were included. Patients with positive or close margins (n = 15) had a significantly lower 10-year CFS rate (46.7% vs. 92.38%; P = .004) than patients with negative margins. This predictive factor remained significant in multivariate analysis (hazard ratio, 9.157; 95% confidence interval, 1.4-60.6). There was no significant difference in the 10-year DFS (33.3% vs. 48.7%; P = .2), DSS (92.8% vs. 100%; P = .1), and OS (92.8% vs. 69.6%; P = .2) rates between these two groups. Neither the initial OIN grade nor other clinical or surgical parameters were found to be significant predictors of outcomes. In this long-term follow-up study on histologically proven OIN treated by primary surgery, positive or close margins status was the only independent predictive factor of progression to cancer. Therefore, we warmly recommand performing re-resection rather than surveillance in cases with positive margins. Oral intraepithelial neoplasia grading or lesion size were not significant predictors of outcomes. 4. Laryngoscope, 2546-2551, 2018.

Malnutrition in patients with breast cancer during treatments (Algeria, 2016)

The aim of this study was to estimate the prevalence of malnutrition in Algerian patients with breast cancer during their treatments at an Anti-Cancer Center in Batna (Algeria). This was a cross-sectional, descriptive survey carried out during 7 months with patients with breast cancer during their treatments, regardless of the disease stage. The evaluation of their nutritional status was carried out according to three approaches: Nutrition Risk Index (NRI) or Buzby Index; objective assessment of nutritional status; Patients Generated-Subjective Global Assessment (PG-SGA). One hundred and sixty-seven patients were included. One of two patients had a total first treatment access period ranging from five months to more than three years from the date of onset of the first symptom seen. More than four of five patients had cancer at invasive (presence of nodules) or metastatic stage. In our study, the NRI allowed to estimate to 53% the prevalence of severe or moderate malnutrition against 63.5% according to the objective method of evaluation. According to the PG-SGA score, 77.2% of the patients were at high risk of malnutrition and 97% needed interventions and/or nutritional recommendations. The high prevalence of malnutrition was, in part, due to the fact that patients presented to treatment at locally advanced or metastatic stages. In order of early detection of situations at risk of malnutrition, the assessment of nutritional status should be an integral part of the overall taken care of patients with breast cancer. L’objectif de cette étude était d’estimer la prévalence de la dénutrition chez des algériennes atteintes de cancer du sein durant leurs traitements dans un Centre Anti-Cancer de Batna (Algérie). Il s’agissait d’une enquête transversale à visée descriptive réalisée durant 7 mois auprès de femmes atteintes de cancer du sein durant leurs traitements. L’évaluation de leur état nutritionnel a été réalisée selon trois approches : Nutrition Risk Index (NRI) ; évaluation objective de l’état nutritionnel ; Patients Generated-Subjective Global Assessment (PG-SGA). Cent-soixante-sept patientes ont été inclues. Une patiente sur deux avait un délai total d’accès aux premiers traitements allant de quatre mois à plus de trois ans à partir de la date de survenue des premiers signes. Plus de quatre patientes sur cinq avaient un cancer au stade invasif ou au stade métastatique. Dans notre étude, le calcul du NRI a permis d’estimer à 53 % la prévalence de dénutrition sévère ou modérée contre 63,5 % selon la méthode d’évaluation objective. Selon le score PG-SGA, 77,2 % des patientes étaient à haut risque de dénutrition et 97 % avaient besoin d’interventions et ou de recommandations nutritionnelles. La prévalence élevée de dénutrition était certainement, en partie, due au fait que les patientes se présentaient aux traitements à des stades localement avancé ou métastatique. Dans le but de dépister précocement les situations à risque de dénutrition l’évaluation de l’état nutritionnel devrait faire partie intégrante de la prise en charge globale des patientes atteintes de cancer du sein.

Thromboembolic (TE) complications in germ cell tumor (GCT) patients: Should use of peripherally inserted central catheters (PICC-Line) be pursued?

571 Background: Patients with GCT receiving cisplatin-based chemotherapy are at high risk of TE events (TEE). Several risk factors have been reported previously, such as cisplatin, Lactate Deshydrogenase, body surf area (BSA)... Methods: we conducted a retrospective study of all patients (pts) with GCT, treated with platinum salts and followed at the university hospital and anticancer center of Bordeaux (June 2007 - January 2015). The following characteristics were recorded: age, performans status, BSA, histological type, site of primitive tumor, stage, prognosis (IGCCCG classification), size of retroperitoneal lymphnode, LDH, type of venous pathway (peripheral vein, implantable venous access port or PICC-Line), prophylaxis of anticoagulant or not, TEE and median time to onset. Results: 206 pts were selected. Thirty-six (17.4%) had one or more venous or arterial TEE during or within 3 months of the end of chemotherapy: 26 deep vein thromboses, 13 pulmonary embolisms and 4 arterial accidents (2 acute limb ischemia and 2 acute coronary syndromes). The median time between treatment initiation and occurrence of TEE was 38.5 days [7-248]. Among the 12 pts with PICC-line, 6 (50%) had a TEE, including 4 cases of pulmonary embolism. In addition to the presence of a PICC-line (OR 4.62 [1.28, 15.56]), factors associated with an increased TE risk in univariate analysis were the use of implantable venous access port (OR: 3.97 [1.81; 9.12]), size of retroperitoneal adenopathy ≥ 2 cm ([2-5 cm]: OR: 24.39 [4.50 - 454.39]; &gt; 5cm : OR : 26.25 [5,00 - 484.5]), stage II (OR : 10.19 [1,9 - 188.96]), stage III (OR :27.2 [5.34 - 479.9]), prognosis group (good : OR : 11.16 [2.16 - 205.04]) ; intermediate : OR : 31.50 [4.81 – 624.20] ; unfavorable : OR : 33.35 [5.7 – 637.34]), VIP (etoposide-ifosfamide-cisplatin) protocol (OR :6.35 [1.51 – 28.15]) and high LDH level (OR :3.88 [1.63 – 10.34]). Conclusions: These results suggest a significant association between PICC-line and the occurrence of TEE in univariate analysis. PICC-line is not risk-free and should be used sparingly in pts with GCT whose treatment objective remains primarily a cure at the cost of less toxicity.

Patterns of Daily Practice of Hormone Therapy in Unfavorable and Favorable Intermediate-Risk Prostate Cancer: Results of the French PROACT Survey

The management of intermediate-risk (IR) prostate cancer (PCa) remains controversial for a subgroup of patients considered as heterogeneous in terms of prognosis. For unfavorable or favorable-IR PCa optimal therapy approach remains to be defined. Two randomized trials have shown improved biochemical control outcomes using external beam radiation therapy (EBRT) and hormone therapy (HT) over EBRT alone. However, physician’s decision to propose HT is not based on a robust rational for a routine practice. Thus, we decided, as academic and private group, to conduct the PROACT survey on pattern and preferences of daily practice in unfavorable and favorable IR PCa patients. The web-questionnaire was distributed to the GETUG, French radiotherapy and the French Association of Urology members. Responses from individual members were registered between January and December 2016. The questionnaire included 4 sections to describe: (i) specialists who prescribe treatments, decisions validation manner and use of guidelines; (ii) definition of IR subsets of patients; (iii) EBRT parameters and the choice of type/duration/sequence of HT and the prescribed drugs; (iv) cardiovascular (CV) and metabolic initial evaluation and follow-up practice. Among the 82 responses recorded, 79 (96%) were radiation oncologists from private or anti-cancer center (72%). HT and irradiation technique/dose/volumes is validated in a specific board meeting in only 45% and 54% of the centers. For prognosis, 76% of the centers declared to identify a subset of IR-patients for a dedicated strategy. The majority of centers consider PSA>15 (77%) and/or Gleason 4+3 (87%) as the main parameters for unfavorable IR definition. Overall, 41% of the centers declared to perform systematically a CV evaluation before HT prescription while 61% take into account the CV history/status to define the type of HT. In addition, CV status (80%) and age (39%) were declared as the main parameters for a specific drug choice. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR. EBRT following hypofractionated schedules is used in only 10% and 14% of the centers and pelvic irradiation in 59% and 18% of the centers for unfavorable and favorable IR-patients, respectively. In terms of follow-up, 80%, 70% and 77% of the centers declared to systematically take into account patients’ weight, lipidic profile and CV status, respectively for follow-up under HT. To our knowledge this is the first survey on the patterns of practice of HT in IR prostate cancer. PROACT survey indicate that ¾ of the French centers declare to identify a subset of unfavorable IR-patients for a specific management. Only 10% of the centers use hypofractionated schedules (2-4Gy/fraction) and half of them include pelvic nodes for unfavorable IR cases. CV status of the patients is considered by the majority of centers as the main factor to determine the type of the drug to use and follow-up after therapy.

Abstract 271: Clinicopathological and molecular study of breast cancer in Algerian women from the Aures region: Data from the anti-cancer center of Batna

Abstract Background:Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. The aim of this study was to analyze the different proportions and distribution of breast cancer molecular subtypes and to determine their associations with some clinical and pathological characteristics in women from the Aures region. We also screened for the prevalence of BRCA1 germline mutations in HBOC patients. Materials and Methods: Clinical and tumor characteristics data of 1144 breast cancer patients were collected from cancer registry of anticancer center of Batna. Breast cancers were diagnosed between 2011 and 2015. Breast cancer subtypes definitions were as follow: Luminal A (ER+ and/or PR+,HER2-), Luminal B (ER+ and/or PR+,HER2+),TNBC (ER-, PR-,HER2-) and HER2+ (ER-, PR-, HER2+). We also compared patients with TNBC and those with other breast cancer subtypes. Differences between the two groups with regard to clinicopathologic parameters: age at diagnosis, menopausal status, histological type, histological grade, breast feeding and oral contraception were examined using Chi square test. BRCA1 was screened by PCR direct sequencing in 22 HBOC patients including all exons where a mutation was previously found in Algerian population (exons 3, 5, 11). Results: The mean age at diagnosis cancer was 48.5 years. Proportions of luminal A, luminal B, TNBC and HER2+ breast cancer subtypes were 47.29%, 21.94%, 21.24% and 9.52%, respectively. We noted a significant difference in the distribution of age at diagnosis among the four cancer subtypes (P = 0.04). Invasive Ductal Carcinoma was the most common histological type in all breast cancer subtypes. Tumors with histological grade 2 and 3 were more common in patients for the four breast cancer subtypes. Our data showed significant differences between premenopausal and postmenopausal status (P=0.00) and tumor histological grade (P&amp;lt;0.03) between TNBC and non TNBC patients. The proportion of premenopausal status was higher in TNBC and non TNBC. Among tumor with histological grade III, TNBC accounted for 33.33% for all TNBC patients and non TNBC accounted for 30.23% for all non TNBC patients. The three BRCA1 recurrent mutations c.83_84delTG, c.181T&amp;gt;G and c.798_799delTT have not been detected in our present study. Conclusion: We report here for the first time, the distribution of molecular subtypes of breast cancer and some clinical and pathological characteristics in a cohort of female breast cancer patients from the Aures region. Interestingly, the proportion of TNBC subtype in women found in our study is similar to African-American breast cancer patients and higher than reported in white women in Europe and America. Further studies are needed to determine the outcome of the different breast cancer subtypes in the Aures region. Large studies of the screening of BRCA1 and BRCA2 genes are on going for the implementation of the genetic testing. Citation Format: Farid Cherbal, Chiraz Mehemmai, Khadidja Gassi, Abdelmoumene Guedioura, Yosr Hamdi, Wassila Benbrahim, Rabah Bakour. Clinicopathological and molecular study of breast cancer in Algerian women from the Aures region: Data from the anti-cancer center of Batna [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 271. doi:10.1158/1538-7445.AM2017-271

Epidemiology of pancreatic cancer

Introduction: With a dramatic increase of incidence and a very poor prognosis, the treatment of pancreatic cancer remains a challenge. Unfortunately, the majority of cases are diagnosed at an advanced stage, where palliative chemotherapy can be administered to alleviate the symptoms and prolong life. Although pancreatic carcinogenesis has not yet been explained, familial aggregation, tobacco smoking, and hypercaloric intake are associated with pancreatic carcinogenesis. Till date, either prevention or screening programs could yet be proposed. Methods: This is a retrospective study for patients following in medical oncology department of anti-cancer center Blida between January 2010- December 2013. The aims of study are to reported the epidemiologic profile for patients with pancreatic cancer Results: 70 patients were following in the department, the median age was 59.8 years [21-80], and sex ratio was 2. Family history of cancer was 16.7%, 29.7% Had diabetes in their antecedents, tobacco smoking was present in 42.8% of cases, 29% of obesity, the most common reasons for consultation were pain in 45.2% and jaundice in 16.4% with an average consultation time of 03 months. The histological type was adenocarcinoma in 95.3% of patients, stage IV and III in 77.5% and 14.3% at diagnosis Conclusion: As the cancer of the pancreas becomes symptomatic the diagnosis is made with a late stage, which testifies to the gravity of this cancer, to improve this situation prevention keeps an important place by acting on the risk factors such as smoking and the obesity

Contribution of BRCA1 and BRCA2 Germline Mutations to Early Algerian Breast Cancer.

Breast cancer is the most common female malignancy and the leading cancer mortality cause among Algerian women. Germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast cancer have not been clearly identified within the Algerian population. It is necessary to study the BRCA1/2 genes involvement in the Algerian breast cancer occurrence. We performed this study to define germline mutations in BRCA1/2 and their implication in breast cancer among young women from eastern Algeria diagnosed or treated with primary invasive breast cancer at the age of 40 or less who were referred to Anti-Cancer Center of Setif, Algeria. Case series were unselected for family history. Eight distinct pathogenic mutations were identified in eight unrelated families. Three deleterious mutations and one large genomic rearrangement involving deletion of exon 2 were found in BRCA1 gene. In addition, four mutations within the BRCA2 gene and one large genomic rearrangement were identified. Novel mutation was found among Algerian population. Moreover, five variants of uncertain clinical significance and favor polymorphisms were identified. Our data suggest that BRCA1/2 mutations are responsible for a significant proportion of breast cancer in Algerian young women.

Fistula-associated anal cancer in the setting of Crohn’s disease

Diagnostic accuracy of inflammatory markers as early predictors of infection after elective colorectal surgery: results from the IMACORS study Pablo Ortega-Deballon, MD, PhD, Olivier Facy, MD, PhD, Brice Paquette, MD, David Orry, MD, Christine Binquet, Patrick Rat, MD University Hospital of Dijon, Dijon, France; University Hospital of Besancon, Besancon France; Georges-Francois Leclerc Anticancer Center, Dijon, France

Abstract 5284: Triple-negative breast cancer in Algerian population: clinicopathological and molecular study

Abstract Background:Triple-negative breast cancer (TNBC),defined by the absence of estrogen receptor (ER), progesterone receptor (PR),and human epidermal growth factor receptor 2 (HER2) expression, accounts for 12% to 20% of all breast cancers.Its prevalence differs between races.TNBC shows substantial overlap with basal-type and BRCA1-related breast cancers and it is associated with early recurrence of disease and poor outcome.In the current study, we sought to compare some clinical and tumor characteristics of breast cancer patients with or without TNBC. We also screened for the prevalence of germline BRCA1 mutations in TNBC patients. Materials and Methods: Clinical and tumor characteristics data of 3403 breast cancer patients were collected from cancer registries of anticancer center of Blida, public hospital of Oued Amizour, anticancer center of Batna and public hospital of Rouiba. Breast cancers were diagnosed between 2007 and 2014. All histopathologic and immunohistochemical diagnoses were reviewed by pathologists. Patients were divided in two groups: those with TNBC and those with other breast cancer subtypes. Differences between the two groups with regard to clinicopathologic parameters: age at diagnosis, menopausal status, histological grade and histological type, were examined using Chi-square test. BRCA1 was screened by PCR-direct sequencing in 56 TNBC patients (26 with a family history of breast cancer and 30 sporadic cases) including all exons where a mutation was previously found in Algerian population (exons 2, 3, 5, 11). Results: The median age at diagnosis for TNBC and non-TNBC patients was 46.96 years and 49.01 years, respectively.The overall prevalence of TNBC was 21.65% (737/3403). Our data showed significant differences in the distribution of age at diagnosis (P&amp;lt;0.0005) and tumor histological grade (P&amp;lt;0.0001) between TNBC and non-TNBC patients.Among tumor with histological grade III,TNBC accounted for 50.54% for all TNBC patients and non-TNBC accounted for 25.28% for all non-TNBC patients.Premenopausal women accounted for 60.71% and 58.9% for all TNBC patients and all non-TNBC patients, respectively. Our data analysis revealed no difference in the distribution of histological tumor type between the two groups.Two BRCA1 mutations, c.83_84delTG and c.2125_2126insA have been detected in two young TNBC patients with a family history of breast cancer. Interestingly, the mutation c.2125_2126insA has been detected in 4 relatives of TNBC proband.Conclusions:This largest Algerian population-based study showed that the prevalence of TNBC in Algerian women is similar to that in African-American patients and higher than reported in white women in Europe and America. The high prevalence of TNBC in Algerian women compared to western countries could be linked to environmental factors and genetic background. Further research is needed to determine long term survival rates in the two groups of breast cancer patients. Citation Format: Farid Cherbal, Hadjer Gaceb, Chiraz Mehemmai, Insaf Saiah, Rabah Bakour, Abdelhalim Ould-Rouis, Tarek Touahria, Hassen Mahfouf, Samia Daoudi, Wassila Benbrahim, Kada Boualga. Triple-negative breast cancer in Algerian population: clinicopathological and molecular study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5284. doi:10.1158/1538-7445.AM2015-5284

Distribution of molecular breast cancer subtypes among Algerian women and correlation with clinical and tumor characteristics: a population-based study.

Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. Molecular classification of breast cancer is an important factor for prognosis and clinical outcome. There are limited data regarding molecular breast cancer subtypes among Algerian women. The objective of the present study was to analyze the proportion and distribution of molecular subtypes and to determine their associations with some clinical and tumor characteristics: age at diagnosis, menopausal status, histological type and histological grade. The study population included 3014 female breast cancers. We analyzed breast cancers from cancer registries of academic medical oncology service of public hospital of Rouiba, anticancer center of Blida, and anticancer center of Batna. Breast cancers were diagnosed between 2008 and 2013. Molecular subtype classification was done based on immunohistochemical surrogates for ER (Estrogen receptor), PR (Progesterone receptor) and HER2 (human epidermal growth factor receptor-2) status obtained from medical records for 3014 breast cancer patients. Breast cancer subtypes definitions were as follow: Luminal A (ER+ and/or PR+, HER2-), Luminal B (ER+ and/or PR+, HER2+), TNBC (ER-, PR - , HER2-), HER2+ (ER-, PR-, HER2+). Molecular subtypes were correlated with the clinicopathological characteristics of the tumors. The mean age at diagnosis cancer was 48.5 years. Proportions of the luminal A, TNBC, luminal B and HER2+ breast cancer subtypes were 50.59%, 20.80%, 19.67% and 8.92%, respectively. We noted a significant difference in the distribution of age at diagnosis among the four cancer subtypes (P= 0.004). Luminal A, Luminal B, TNBC and HER2+ subtypes were significantly different by premenopausal and postmenopausal status (P= 0.01). Invasive Ductal Carcinoma was the most common histological type in all breast cancer subtypes. Tumors with histological grade 2 and 3 were more common in patients for the four breast cancer subtypes. For the first time, we report the distribution of molecular breast cancer subtypes and their associations with some clinicopathological characteristics in a large cohort of Algerian women. In our current study, the median age of diagnosis for all breast cancer subtypes was younger than the average age in Europe and America. Luminal A was the most common sub- type in our patients followed by TNBC. The proportion of luminal A subtype was lesser than reported in white women with breast cancer in Europe and America. The proportion of TNBC subtype in Algerian women was higher compared with Caucasian women of European ancestry. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for Algerian breast cancer patients.

Abstract 3833: Molecular subtypes of breast cancer in Algeria: a population-based study of 3014 women

Abstract Background:Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. Molecular classification of breast cancer is an important factor for prognosis and clinical outcome.To our best knowledge,few studies have been reported on molecular subtypes of female breast cancer in Algeria.The objective of the present study was to evaluate age at diagnosis,distribution,prevalence, and association with menopausal status, histological type and histological grade of molecular subtypes of breast cancer in Algerian women.In addition, we screened for the prevalence of BRCA1 mutations in TNBC patients with and without family history of breast cancer. Methods: We analyzed breast cancers from cancer registries of academic medical oncology service of public hospital of Rouiba, anticancer center of Blida, and anticancer center of Batna.Breast cancers were diagnosed between 2008 and July 2013. ER (oestrogen receptor), PR (progesterone receptor) and HER2 (human epidermal growth factor receptor-2) status were obtained from medical records for 3014 patients.Breast cancer subtypes definitions were as follow:Luminal A (ER+ and/or PR+,HER2-), Luminal B (ER+ and/or PR+,HER2+),TNBC(ER-,PR-,HER2-), HER2+ (ER-,PR-,HER2+). 20 TNBC patients with family history of breast cancer and 33 sporadic TNBC women were screened by using PCR-direct sequencing for 3 common BRCA1 mutations c.83_84delTG, c181T&amp;gt;G and c.798_799delTT detected in previous studies in Algerian population. Results: The median age at diagnosis of 3014 patients with breast cancer was 48.5 years. The prevalence of the Luminal A, TNBC, Luminal B and HER2+ were 50.59%,20.80%, 19.67% and 8.92%,respectively.Luminal A, Luminal B, TNBC and HER2+ subtypes were more prevalent among premenopausal women (29.24%, 13.26%, 12.19% and 4.80%) compared with postmenopausal women (21.74%, 7.31%, 7.89% and 3.87%). Invasive Ductal Carcinoma was the most prevalent histological type in all breast cancer subtypes at any age. Tumors with histological grade 2 were more prevalent in younger patients for the four breast cancer subtypes. High prevalence of histological grade 3 was showed in older patients. The BRCA1 mutation c.83_84delTG was detected in one young TNBC patient with a family history of cancer. Conclusion: For the first time, we report the distribution of molecular subtypes of breast cancer and some clinical characteristics in a large cohort of Algerian women. In our current study, the median age of diagnosis for all breast cancer subtypes was younger than the average age in Europe and America.Interestingly, TNBC subtype was the second most prevalent in our patients,and the prevalence of luminal subtype was lesser than reported in white women with breast cancer in Europe and America. The high prevalence of TNBC reported here could be linked to Sub-Saharan African genetic elements of Algerian population.Screening for BRCA1 mutations in large series of TNBC patients is ongoing. Citation Format: Farid Cherbal, Hadjer Gaceb, Chiraz Mehemmai, Rabah Bakour, Kada Boualga, Wassila Benbrahim, Hassen Mahfouf. Molecular subtypes of breast cancer in Algeria: a population-based study of 3014 women. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3833. doi:10.1158/1538-7445.AM2014-3833

942TiP - Encourage: the Use in Routine Practice of Bevacizumab in First-Line Therapy for Patients with Ovarian Cancer– a Gineco Prospective Cohort Study

ABSTRACT Background: The two phase III first-line trials GOG 218 and ICON 7 met their primary progression free survival endpoint, leading to an European Union approval in december 2011 of bevacizumab in combination with carboplatin and paclitaxel during 6 cycles, followed by a maintenance period for a total time of 15 months for the treatment of patients with FIGO IIIb-IV stage ovarian cancer. The ENCOURAGE prospective, multicenter cohort study has been developped to describe bevacizumab administration in ovarian cancer, in the daily practice, outside of trials with their usual patient selections and specific follow-up methods Trial design: A total number of 500 patients with ovarian cancer, treated with bevacizumab in first-line, in 100 French centers, will be included. Investigators will record the reasons why they indicate or exclude bevacizumab administration in the first-line treatment strategy of each of their patients with ovarian cancer. The primary endpoint is to report the cardio-vascular, renal and digestive toxicity of bevacizumab delivered in a wide scape of French centers (academic or not hospitals, private clinics, anticancer centers). The secondary endpoints include evaluation in real life of bevacizumab use in ovarian cancer treatment in first-line (the characteristics of the treated population, the reason of non administration of bevacizumab in first line), the modalities of use and the monitoring pratices. At last, the efficacy of the bevacizumab treatment strategy will be also evaluated by analysing the progression free survival in both first line and relapse with or without bevacizumab. From April 2013, to April 2014, more than 200/500 patients have been registered. Disclosure: I.L. Ray-Coquard: Roche, Pharmamar, Amgen, AstraZeneca board and lecture; A. Floquet: Investigator fees and congress participation support in Roche Clinical Studies; J. Alexandre: I am a member of an advisory board concerning bevacizumab. All other authors have declared no conflicts of interest.