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BACKGROUND: The phase III PAOLA-1/ENGOT-ov25 study (NCT02477644) showed that addition of olaparib to bevacizumab maintenance improved progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer. We evaluated maintenance olaparib plus bevacizumab in older patients in PAOLA-1. METHODS: Baseline clinical and molecular data, and PFS, were compared between older (aged ≥65 years) and younger patients (

OBJECTIVES: Adding maintenance olaparib to bevacizumab provided a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the randomized, double-blind PAOLA-1/ENGOT-ov25 trial (NCT02477644). We analyzed PFS by clinical risk and biomarker status. METHODS: Patients received olaparib 300 mg twice daily for up to 24 months plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total, or placebo plus bevacizumab. This post hoc exploratory analysis evaluated PFS in patients classified as higher risk (stage III with upfront surgery and residual disease or neoadjuvant chemotherapy; stage IV) or lower risk (stage III with upfront surgery and no residual disease), and by biomarker status. RESULTS: Of 806 randomized patients, 74% were higher risk and 26% were lower risk. After a median 22.9 months of follow-up, PFS favored olaparib plus bevacizumab versus placebo plus bevacizumab in higher-risk patients (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.49-0.74) and lower-risk patients (0.46; 0.30-0.72). Olaparib plus bevacizumab provided a substantial PFS benefit versus bevacizumab alone in the homologous recombination deficiency (HRD)-positive subgroup (higher risk: HR 0.39; 95% CI 0.28-0.54 and lower risk: 0.15; 0.07-0.30), with 24-month PFS rates in lower-risk patients of 90% versus 43%, respectively (Kaplan-Meier estimates). CONCLUSIONS: In PAOLA-1, maintenance olaparib plus bevacizumab provided a substantial PFS benefit in HRD-positive patients with a reduction of risk of progression or death of 61% in the higher-risk group and of 85% in the lower-risk group compared with bevacizumab alone. ispartof: GYNECOLOGIC ONCOLOGY vol:164 issue:2 pages:254-264 ispartof: location:United States status: published

Background and aims: Pancreatic cancer is highly lethal and often diagnosed at an advanced stage. This cohort study analyzes the impact of care pathways, delays, and socio-spatial determinants on pancreatic cancer patients’ diagnosis, treatment, and prognosis. Method: Patients with pancreatic adenocarcinoma newly diagnosed at all stages between January and June 2016 in the AuRA French region were included. The influence on survival of delays of care, healthcare centers’ expertise, and socio-spatial determinants was evaluated. Results: Here, 538 patients were included in 76 centers including 116 patients (21.8%) with resectable, 64 (12.0%) borderline-resectable, 147 (27.6%) locally-advanced tumors, and 205 (38.5%) with metastatic disease. A delay between first symptoms and CT scans did not statistically influence overall survival (OS). In resected patients, OS was significantly higher in centers with more than 20 surgeries (HR 20 surgeries/year p = 0.0081). Regarding socio-spatial determinants, patients living in municipalities with greater access to a general practitioner (HR = 1.673, p = 0.0153) or with a population density below 795.1 people/km2 (HR = 1.881, p = 0.0057) were significantly more often resectable. Conclusion: This cohort study supports the pivotal role of general practitioner in cancer care and the importance of the centralization of pancreatic surgery to optimize pancreatic cancer patients’ care and outcomes. However, delays of care did not impact patient survival.

Background Over 30 million COVID-19 cases have been diagnosed worldwide from late 2019. Among frail persons, cancer patients are at high risk of death from COVID-19. Methods The French prospective cohort ONCOVID-19 enrolled patients with solid or haematological tumour, receiving anticancer treatment and presenting with clinical symptoms suggestive of COVID-19. COVID-19 was confirmed through detectable SARS-CoV2 by RT-PCR (repeated twice if negative first) and/or specific CT-scan. The study aims to assess the 28-day mortality rate after the first COVID test. Results From March 1st to May 21st 2020, 23 French cancer centres and hospitals enrolled 1230 cancer patients with suspicion of COVID-19, including 1162 (94.5%) matching the inclusion criteria. We identified 425 (36.6%) COVID-19 positive patients including 155 (13.3%) diagnosed with CT-scan only, while 737 (63.4%) patients were COVID-19 negative. Death at day-28 occurred in 116/425 (27.8%) COVID-19 positive patients, and in 118/737 (16.3%) COVID-19 negative patients (p

International audience; Ethnopharmacological relevance: In French Guiana, traditional phytotherapies are an important part of self-healthcare, however, a precise understanding of the interactions between local phytotherapies and biomedicine is lacking. Malaria is still endemic in the transition area between French Guiana and Brazil, and practices of self-treatment, although difficult to detect, have possible consequences on the outcome of public health policies.Aim of the study: The objectives of this research were 1) to document occurences of co-medication (interactions between biomedicine and local phytotherapies) against malaria around Saint-Georges de l’Oyapock (SGO), 2) to quantify and to qualify plant uses against malaria, 3) and to discuss potential effects of such co-medications, in order to improve synergy between community efforts and public health programs in SGO particularly, and in Amazonia more broadly.Materials and methods: This cross-sectional study was conducted in 2017 in SGO. Inhabitants of any age and nationality were interviewed using a questionnaire (122 questions) about their knowledge and habits regarding malaria, and their use of plants to prevent and treat it. They were invited to show their potential responses on a poster illustrating the most common antimalarial plants used in the area. In order to correlate plant uses and malaria epidemiology, all participants subsequently received a medical examination, and malaria detection was performed by Rapid Diagnostic Test (RDT) and Polymerase Chain Reaction (PCR).Results: A total of 1566 inhabitants were included in the study. Forty-six percent of them declared that they had been infected by malaria at least once, and this rate increased with age. Every person who reported that they had had malaria also indicated that they had taken antimalarial drugs (at least for the last episode), and self-medication against malaria with pharmaceuticals was reported in 142 cases. A total of 550 plant users was recorded (35.1% of the interviewed population). Among them 95.5% associated pharmaceuticals to plants. All plants reported to treat malaria were shared by every cultural group around SGO, but three plants were primarily used by the Palikur: Cymbopogon citratus, Citrus aurantifolia and Siparuna guianensis. Two plants stand out among those used by Creoles: Eryngium foetidum and Quassia amara, although the latter is used by all groups and is by far the most cited plant by every cultural group. Cultivated species accounts for 91.3% of the use reports, while wild taxa account for only 18.4%.Conclusions: This study showed that residents of SGO in French Guiana are relying on both traditional phytotherapies and pharmaceutical drugs to treat malaria. This medical pluralism is to be understood as a form of pragmatism: people are collecting or cultivating plants for medicinal purposes, which is probably more congruent with their respective cultures and highlights the wish for a certain independence of the care process. A better consideration of these practices is thus necessary to improve public health response to malaria.

Background BRAF mutations occurring in 1%–5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSe vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. Patients and methods Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). Results Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%–54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8–6.8), and OS was 10 months (95% CI 6.8–15.7). The vemurafenib safety profile was consistent with previous publications. Conclusion Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. Trial registration ClinicalTrials.gov identifier: NCT02304809.

Background The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. Patients and methods The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. Results A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. Conclusions In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years., Highlights • A reduction of the number of cancer patients attending cancer centers was observed in France from January to July 2020. • This reduction was observed only for newly diagnosed patients. • The reduction of new diagnosis was more pronounced in women, for breast cancer, and prostate cancer, and nonmetastatic cancer. • No compensation was observed for the last months of 2020. The magnitude of delays may be larger in centers within the same country. • An estimation of the excess cancer death resulting from these delays is presented.

Objective : Influenza has been shown to increase the risk for severe bacterial infection, in the tropics the seasonality of influenza epidemics is less marked and this may not be the case. Dengue is often followed by prolonged asthenia and some physicians hypothesized increased susceptibility to infections based on anecdotal observations. Time series of influenza and dengue surveillance were confronted with bacterial sepsis admissions to test the hypotheses. Monthly surveillance data on influenza and dengue and aggregated sepsis data in Cayenne hospital were matched between 24/10/2007 and 27/09/2016. An ARIMA (1,0,1) model was used. Results : The series of the number of monthly cases of sepsis was positively associated with the monthly number of cases of influenza at time t (β=0.001, p=0.0359). Forecasts were imperfectly correlated with sepsis since influenza is not the only risk factor for sepsis. None of the ARIMA models showed a significant link between the dengue series and the sepsis series. There was thus no link between dengue epidemics and sepsis but it was estimated that for every 1000 cases of flu there was one additional case of sepsis. In this tropical setting, influenza was highly seasonal, and improved vaccination coverage could have benefits on sepsis.

International audience; To implement future malaria elimination strategies in French Guiana, a characterization of the infectious reservoir is recommended. A cross-sectional survey was conducted between October and December 2017 in the French Guianese municipality of St Georges de l'Oyapock, located along the Brazilian border. The prevalence of Plasmodium spp. was determined using a rapid diagnostic test (RDT) and a polymerase chain reaction (PCR). Demographic, house locations, medical history, and biological data were analyzed. Factors associated with Plasmodium spp. carriage were analyzed using logistic regression, and the carriage localization was investigated through spatial cluster analysis. Of the 1,501 samples analyzed with PCR, positive results totaled 90 and 10 for Plasmodium vivax and Plasmodium falciparum, respectively. The general PCR prevalence was 6.6% [5.3-7.9], among which 74% were asymptomatic. Only 13/1,549 were positive by RDT. In multivariate analysis, participants older than 15 years, living in a remote neighborhood, with a prior history of malaria, anemia, and thrombocytopenia were associated with an increased odds of Plasmodium spp. carriage. High-risk clusters of P. vivax carriage were detected in the most remote neighborhoods on the village outskirts and two small foci in the village center. We also detected a hot spot for both P. vivax and P. falciparum symptomatic carriers in the northwestern part of the village. The present study confirms a wide-scale presence of asymptomatic P. falciparum and P. vivax carriers in this area. Although they were more often located in remote areas, their geographic distribution was spatially heterogeneous and complex.

(1) Objectives: French Guiana is the French territory most affected by sickle cell disease (SCD). This study investigates the associations between different environmental factors relative to climate, infectious outbreaks, and emergency visits or weekly hospital admissions for vaso-occlusive crisis (VOC). The identification of risk factors would lead to better patient care and patient management, and more targeted prevention and therapeutic education for patients with SCD in French Guiana. (2) Methods: This study was performed using data collected from the medicalized information system and emergency medical records of Cayenne General Hospital, between 1 January 2010 and 31 December 2016. ARIMA models were used to investigate the potential impact of weather conditions and flu epidemics on VOC occurrence. (3) Results: During the study period, 1739 emergency visits were recorded among 384 patients, of which 856 (49.2%) resulted in hospitalization, 811 (46.6%) resulted in hospital discharge, and 72 (4.2%) in another orientation. Decreased temperature and decreased humidity were both independent factors associated with an increase of VOC cases (p = 0.0128 and p = 0.0004, respectively). When studying severe VOC (leading to hospitalization, with or without prior emergency visit), 2104 hospital admissions were recorded for 326 patients. The only factor associated with severe VOC, in the multivariate analysis, was flu epidemics (p = 0.0148). (4) Conclusions: This study shows a link between climate, flu epidemics, and VOC in French Guiana. Patient&rsquo, s awareness of risks related to climate and flu epidemics should be encouraged, as home prevention measures can help avoid painful crises. Moreover, physicians should encourage patients to get immunized for influenza every year.

Resume Vingt-cinq a soixante-cinq pour cent des patientes presentent une douleur chronique apres cancer du sein. Le traitement associe medicaments antalgiques et techniques psychocorporelles. Hypothese L’osteopathie ameliore le controle des douleurs et la qualite de vie des patientes. Methode Etude randomisee prospective monocentrique comparant un traitement antalgique standard (bras A) a un traitement antalgique standard + osteopathie, debute entre un et douze mois apres la chirurgie. Objectif principal Intensite de la douleur (EVA a trois mois [j90]). Objectifs secondaires Douleur (EVA) a six et douze mois, consommation d’antalgiques, anxiete/depression (HADS-Hospital Anxiety and Depression Scale), qualite de vie (QLQ-C30). Quatre-vingt patientes prevues pour une difference EVA de deux points (alpha bilateral 5 %, puissance 90 %). Resultats Vingt-huit patientes (14 par bras) ont ete incluses d’avril 2011 a fevrier 2014, imposant l’arret de l’etude. A j90, le niveau de douleur a l’EVA n’etait pas different entre les deux bras (p = 0,258), de meme qu’a six et douze mois. L’evolution du score de depression HADS entre l’inclusion et j90 etait plus favorable dans le bras B (p = 0,049). Le score global de qualite de vie etait meilleur dans le bras B a j90 (p = 0,015), ainsi que le sous-score douleur (p = 0,021). Discussion Les patientes sont demandeuses de therapies complementaires. Peu d’etudes existent. Notre etude s’est heurtee a des difficultes majeures de recrutement, ce qui limite l’interpretation des resultats. Malgre l’absence de difference sur l’objectif principal, des elements (QV, depression) sont a noter en faveur de l’osteopathie. Des etudes multicentriques sont necessaires.

International audience; BACKGROUND: Prisoners in French Guiana, a French territory located in South America, have a HIV and hepatitis B prevalence of 4%. Body modifications such as penile implants, tattoos, and body piercings are common among detainees, increasing the risk of blood-borne virus transmission.METHODS: We conducted a cross-sectional randomised survey in which the primary objective was to estimate the prevalence of high risk 'bloody practices' (penile implants, tattoos, body piercings) in French Guiana's only correctional facility. The secondary objective was to describe the risk factors for penile implants, the procedures and motivations for insertion, the reported complications, their risk factors and adverse impact on condom use.RESULTS: Of the 221 male inmates interviewed, 19% had tattoos or body piercings while incarcerated, and 68% had penile implants, of which, 85% had been inserted inside the correctional facility. Addictive behaviors such as cannabis use and alcohol addiction (positive AUDIT-C score), early age at first sexual intercourse, and the number of incarcerations correlated positively with having inserted one or more penile implants while incarcerated. In contrast, having reported previous psychiatric hospitalizations and having a high knowledge score for HIV/AIDS and sexually transmitted infections (STIs) were negatively correlated with the insertion of penile implants while incarcerated. Penile implants were inserted in poor hygienic conditions, usually using the sharp lid of a canned food container, with 18% of early complications, mostly haemorrhage and edema. Condom use was negatively impacted for 52% of men with penile implants.CONCLUSIONS: Our results highlight the need for prevention interventions which should aim at increasing knowledge levels and at implementing comprehensive risk-reduction measures.

International audience; OBJECTIVE:The overall rate of suicide in French Guiana is estimated at 6 per 100,000, a rate that is lower than in mainland France. Given the frequent reports of suicide in Amerindian communities, our hypothesis was that this figure fails to capture a more contrasted reality. Our objective was to refine estimates and determine suicide rates in remote villages of French Guiana.METHODS:We included patients for whom a suicide attempt or suicide was mentioned in medical records. The Health centers were grouped into two zones according to geographical remoteness.RESULTS:The highest suicide rates observed in the remote Amerindian villages of Camopi and Trois Sauts were, respectively, 118 and 78/100,000. The median age at the time of suicide was significantly younger in remote zones [23 years (95% CI 21.59-25.06)] than in non-remote zones-[27 years (95% CI 24.47-29.31)]. The most frequent methods were hanging (78%) and intoxication (22%).CONCLUSIONS:The suicide rate in remote areas in French Guiana was eight times higher than in France. The suicide of young people in remote areas in French Guiana and specifically in Amerindian villages must be better understood and prevented with contextualized and adapted care.

Summary Background Fungal infections remain a major contributor to the opportunistic infections that affect people living with HIV. Among them, histoplasmosis is considered neglected, often being misdiagnosed as tuberculosis, and is responsible for numerous deaths in Latin America. The objective of this study was to estimate the burden of HIV-associated histoplasmosis compared with tuberculosis in Latin American countries. Methods For this modelling study, we estimated prevalence of previous exposure to Histoplasma capsulatum , HIV-associated histoplasmosis annual incidence, and number of deaths in 2012 in Latin American countries based on historical histoplasmin skin test studies in the general population, with an antigen dilution level of more than 1/10. Studies were identified in a literature search. Data on HIV-associated tuberculosis were extracted from the WHO notifications and outcomes tables and data on people living with HIV were extracted from the UNAIDS report for the year 2012. We systematically propagated uncertainty throughout all the steps of the estimation process. Findings Among 1310 articles identified as of June 1, 2015, 24 articles were included in the study, representing 129 histoplasmin skin test studies led in the general population of Latin American countries. For the year 2012, we estimated a range of 6710 (95% CI 5680–7867) to 15 657 (13 254–18 357) cases of symptomatic HIV-associated histoplasmosis in Latin America. Hotspot areas for histoplasmosis prevalence (>30%) and incidence (>1·5 cases per 100 people living with HIV) were Central America, the northernmost part of South America, and Argentina. According to realistic scenarios, we estimated a range of 671 (95% CI 568–787) to 9394 (7952–11 014) deaths related to histoplasmosis, compared with 5062 (3777–6405) deaths related to tuberculosis reported in Latin America. Interpretation Our estimates of histoplasmosis incidence and deaths are high and consistent with published data. For the first time, the burden of histoplasmosis is estimated to be equivalent in incidence and even higher in deaths when compared with tuberculosis among people living with HIV in Latin America. Funding None.

Introduction Malgre une diminution constante du nombre de cas de paludisme observes depuis les annees 2000 en Guyane, des foyers endemiques persistent notamment a sa frontiere avec le Bresil. Les objectifs de ce travail etaient de decrire les connaissances des habitants de la commune frontaliere de Saint-Georges de l’Oyapock (STG) vis a vis du paludisme. Dans un deuxieme temps, les caracteristiques socio-demographiques et les comportements de ceux ayant un bon niveau de connaissances ont ete compares a ceux ayant un mauvais niveau afin d’adapter secondairement les politiques publiques de prevention. Materiels et methodes L’etude a ete conduite entre septembre et decembre 2017 dans les quartiers de STG ou l’incidence du paludisme etait la plus elevee les trois annees precedentes. L’enquete portait sur les connaissances, attitudes et pratiques (CAP) vis a vis du paludisme des habitants de STG âges de plus de 15 ans. Les donnees ont ete collectees grâce a un questionnaire administre par des mediateurs formes et issus des communautes. Les donnees relatives aux connaissances ont ete etudiees a l’aide de methodes statistiques exploratoires. Elles ont ete resumees, testees puis ont fait l’objet d’etudes bivariees. Resultats L’âge moyen des 844 habitants de STG inclus etait de 37,2 ans (15,8). Le sex-ratio etait de 0,7 et 485 personnes (57,5 %) se declaraient de nationalite bresilienne. Au total, 251/844 (29,7 %) avaient un faible niveau de connaissances. Les symptomes de la maladie etaient mal connus pour 213/844 personnes (25,2 %), les mesures de prevention pour 378/844 (44,7 %) et 206/844 (24,4 %) ne savaient pas qu’on pouvait mourir du paludisme. Les personnes âgees de moins de 25 ans, vivant dans un quartier amerindien ou parlant une langue amerindienne, les agriculteurs, les personnes retraites ou restant a domicile, les personnes en lien avec l’exploitation aurifere avaient niveau de connaissances significativement moins bon. Conclusion L’etude des connaissances d’une population de Guyane francaise vivant en zone d’endemie a permis de montrer pour la premiere fois un niveau de connaissance tres limite vis a vis du paludisme. Ce niveau de connaissance etant, par ailleurs, essentiellement et paradoxalement observe chez les populations les plus a risque notamment les populations autochtones, les jeunes et les orpailleurs. Il est donc souhaitable de renforcer, diversifier et adapter aux differentes cultures les messages de prevention et de promotion de la sante pour les rendre plus efficaces.

Introduction La Guyane francaise est une zone de moyenne a faible risque de transmission du paludisme. Dans ces regions de faible endemie, la majorite des infections, notamment a Plasmodium vivax (Pv), sont asymptomatiques et constituent ainsi le reservoir parasitaire pouvant sporadiquement generer des episodes epidemique. Dans une logique de controle et d’elimination du paludisme la caracterisation de ce reservoir et des facteurs de risque associes est primordiale. Materiels et methodes Une etude transversale a ete menee d’octobre a decembre 2017 a Saint Georges de l’Oyapock (STG) situee a la frontiere bresilienne en Guyane, en population generale. La prevalence de portage a ete determinee par TDR et PCR en temps reel sur sang total. La localisation GPS des habitations, les donnees socio-demographiques, biologiques et cliniques ont ete recueillies et comparees au portage ou non de plasmodies. L’analyse spatiale avec determination des clusters a ete realisee grâce a la methode de Bernoulli au sein du logiciel SaTScan. Resultats Au total, 1566 participants ont etes inclus sur une population de 2727 habitants. La moyenne d’âge etait de 22 ans [IQ : 22,1–24,0], le sexe ratio etait de 0,88. La population etait pluri-ethnique, principalement de nationalite francaise (56,7 %) et bresilienne (42,7 %). Un tiers (35,3 %) avait un antecedent de paludisme dans les trois dernieres annees dont la majorite etait due a Pv. Par TDR, seulement 0,8 % (13/1549) des patients etaient positifs. Par PCR, le portage a ete identifie chez 100/1501 des personnes testees (6,6 %). Parmi celles-ci, 90 % etaient positives a Pv et 10 % a P. falciparum (Pf). La prevalence de portage etait tres variable selon les quartiers allant de 0 % a 29,5 %. Deux clusters significatifs ont ete retrouves a Blondin 2 et Trois paletuviers, les deux quartiers les plus isoles de STG. Deux micro-clusters familiaux ou communautaires et un dernier plus vaste ont egalement ete identifies au centre et nord du village. La majorite des infections etaient asymptomatiques (75 %). L’analyse multivariee retrouvait comme principaux facteurs de risque de portage : un âge superieur a 15 ans, habiter dans un quartier isole, la presence d’antecedents de paludisme, la presence d’une anemie et d’une thrombopenie. L’utilisation de moustiquaire n’etait pas retrouvee comme facteur protecteur du portage. Conclusion Le portage de paludisme dans cette zone frontaliere est tres heterogene et associe, a des zones de forte transmission dans les zones d’habitats isoles. Il est associe egalement a des cytopenies tant pour Pv que pour Pf. Un traitement de tous les portages dont ceux asymptomatiques a ete realise ; l’impact de cet attitude sera evaluee a un an afin de discuter l’interet de ce type d’intervention dans un objectif d’elimination du paludisme.

Introduction La Guyane est le departement francais le plus affecte par le VIH et est egalement largement impacte par le VHB. En prison, les prevalences du VIH et du VHB fluctuaient autour de 4 % en 2014. Les pratiques sanglantes, telles que la pose d’implants peniens, les tatouages et les piercings sont des pratiques courantes parmi les prisonniers et peuvent accroitre les risques de maladies transmissibles par le sang. Materiels et methodes En 2015 une etude transversale a ete conduite a la seule prison de Guyane. Cette etude avait pour objectif d’estimer la prevalence des pratiques sanglantes en prison et s’interessait plus particulierement aux implants peniens. Les facteurs associes a la pose d’implants peniens et aux complications eventuelles ont ete recherches. Resultats Parmi les 221 hommes incarceres interroges, 19 % avaient ete tatoues ou avaient fait un piercing en prison, 68 % avaient des implants peniens, parmi lesquels 57 % avaient ete poses en prison. Les comportements addictifs, tels que la consommation de cannabis et la dependance a l’alcool, un âge precoce au premier rapport sexuel et le nombre d’incarceration etaient positivement correles au fait d’avoir des implants peniens. A l’inverse, avoir ete hospitalise pour troubles psychiatriques et avoir un score eleve de connaissance vis-a-vis des modes de transmission et de prevention du VIH et des IST etaient negativement correles au fait d’avoir des implants peniens. Les implants peniens etaient souvent poses dans de mauvaises conditions d’hygiene, a l’aide d’un couvercle de boite de conserve, 18 % declaraient avoir eu des complications au moment de la pose, principalement des hemorragies et des gonflements. Cinquante deux pourcents des hommes interroges rapportaient des difficultes a utiliser un preservatif suite a la pose de leurs implants peniens. Conclusion Nos resultats mettent en lumiere une prevalence des pratiques sanglantes, notamment des implants peniens, tres elevee ainsi que les risques a plus ou moins long terme lies a ces pratiques. Ils mettent egalement en avant « l’impregnation carcerale » comme facteur determinant de ces pratiques sanglantes. Il est necessaire de mettre en place des interventions de prevention ciblees, impliquant les prisonniers, qui viseraient a augmenter le niveau de connaissances mais egalement de mettre en place des mesures plus globales de reduction des risques lies a ces pratiques sanglantes en prison, en passant en premier lieu par une prise en compte de cette problematique dans les recommandations officielles.

Background: Decrease of circulating tumor cells (CTC) during treatment is an independent prognostic factor in metastatic breast cancer (MBC). We specifically evaluated the impact of CTC on brain metastasis outcome. Methods: HER2-positive MBC with brain metastasis not previously treated with whole-brain radiotherapy received firstline combination of lapatinib and capecitabine in a phase II study. CTC were detected at baseline and day 21 (CellSearch). Results: Median follow-up of the 44 analyzed patients was 21.2 months. The central nervous system objective response (CNS-OR) rate was 66%. At baseline, 20 of 41 assessable patients for CTC (49%) had ≥1 CTC (range 1–301, median 3) and 9 (22%) had ≥5 CTC. At day 21, 7 of 38 patients (18%) had ≥ 1C TC (P = 0.006, versus baseline), and CTC had disappeared in 11 patients. CNS-OR rate was significantly higher in patients with no CTC at day 21 [25 of 31 (80%) versus 2 of 7 (29%), P= 0.01]. The 1-year overall survival rate was 83.9% in patients with no CTC at day 21 versus 42.9% in patients with ≥ 1C TC (P= 0.02). Conclusions: This is the first report showing a correlation between CNS metastasis response, outcome and early CTC clearance under targeted treatment of HER2+ MBC. Clinical Trials number: NCT00967031.

Purpose The outcome of sarcoma has been suggested in retrospective and non-exhaustive studies to be better through management by a multidisciplinary team of experts and adherence to clinical practice guidelines (CPGs). The aim of this prospective and exhaustive population based study was to confirm the impact of adherence to CPGs on survival in patients with localized sarcoma. Experimental design Between 2005 and 2007, all evaluable adult patients with a newly diagnosis of localized sarcoma located in Rhone Alpes region (n = 634), including 472 cases of soft-tissue sarcoma (STS), were enrolled. The prognostic impact of adherence to CPGs on progression-free survival (PFS) and overall survival (OS) was assessed by multivariate Cox model in this cohort. Results The median age was 61 years (range 16-92). The most common subtypes were liposarcoma (n = 133, 28%), unclassified sarcoma (n = 98, 20.7%) and leiomyosarcoma (n = 69, 14.6%). In the initial management phase, from diagnosis to adjuvant treatment, the adherence to CPGs for patients with localized STS was 36% overall, corresponding to 56%, 85%, 96% and 84% for initial surgery, radiation therapy, chemotherapy and follow-up, respectively. Adherence to CPGs for surgery was the strongest independent prognostic factor of PFS, along with age, gender, grade, and tumor size. For OS, multivariate analysis adherence to CPGs for surgery was a strong independent prognostic factor, with an important interaction with a management in the regional expert centers. Conclusions This study demonstrates impact of CPGs and treatment within an expert center on survival for STS patients in a whole population-based cohort.

International audience; BACKGROUND: Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. PATIENTS AND METHODS: In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. RESULTS: The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. CONCLUSION: In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. CLINICALTRIALSGOV: NCT01303679

Background: The LANDsCAPE phase II study showed that C+L had a significant antitumor activity in previously untreated brain metastases (BM) from HER2-positive breast cancer (BC), with a central nervous system-objective response rate (CNS-ORR) of 67% and a median time to whole-brain radiotherapy (WBRT) of 8.3 months (43 analysed pts). Thus initial C+L combination might be a viable alternative to immediate WBRT in this setting. In this study, serum samples were collected before and during treatment for proteomic-based approaches to identify predictive biomarkers of treatment response. Methods: Baseline (BL) and day 21 (D21) serum samples from highly responsive (R, CNS lesions -volumetric response ≥ 75%, n=6) and non-responsive (NR, CNS-stable or progressive disease, n=6) pts were subjected to isobaric Tag for Relative and Absolute Quantification (iTRAQ)-based proteomics. Samples from each condition were pooled to constitute 4 independent mixes ((BL-R, D21-R, BL-NR and D21-NR). Each of them underwent immuno-depletion of highly abundant proteins, concentration, reduction, alkylation and tryptic digestion. Then, each mix was fractionated and subjected to iTRAQ identification and quantitation using nano-liquid chromatography (LC) and electrospray ionisation (ESI)-orbitrap tandem mass spectrometry (MS/MS) (LTQ-orbitrap, Thermofisher). Differentially expressed proteins were analysed using IPA (Ingenuity® Systems) to highlight biological functions and signalling pathways that were most significantly enriched. Results: iTRAQ-based measurements identified serum proteins with significant (fold-change > 1.5 and p-value < 0.05) differential expression between BL and D21, in R- (n = 38 proteins) and NR- pts (n = 18 proteins). At baseline, 30 proteins were differentially expressed between R-and NR-pts. Among the most differentially expressed proteins, some had been previously described as involved in cancer metastases (between BL and D21: tenascin C, neuropilin-1, Serpin A1, Cathepsin S, prostaglandin D2 synthase, melanoma cell adhesion molecules, procollagen C-endopeptidase enhancer; between R and NR: carnosine dipeptidase 1, endothelial protein C receptor, matrix metallopeptidase 9, cystatin C, lumican, plexin B2, Insulin-like growth factor binding protein acid labile subunit, pro-platelet basic protein, cadherin 5, Protein S). Proteins with differential expression during treatment were involved in various biological processes, including lipid metabolism, small molecule biochemistry, molecular transport, gene expression, cellular growth and proliferation, cellular movement and cancer, as well as various canonical pathways such as acute phase response signalling, LXR/RXR activation and complement system. Interestingly, and as opposed to NR-pts, R-pts specifically showed an overall increase in proteins of acute phase response, with a significant decrease in C-reactive protein (CRP). Conclusion: iTRAQ-based quantitative proteomics identify serum proteins that could predict the therapeutic response to C+L combination in untreated BM from HER2-positive BC. If validated, such biomarkers may help to select the best therapeutic strategy in this setting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-01.

Background: Decrease of CTC level during treatment in MBC has been reported as an independent prognostic and predictive factor of patients’ outcome. Monitoring CTC in addition to clinical response criteria is currently evaluated in early clinical trials in various cancer types. We sought to evaluate the clinical interest of peripheral blood CTC for patients included in the LANDSCAPE study which assessed the efficacy of upfront systemic treatment with L+C for newly diagnosed brain metastasis. Methods: This analysis is a preplanned secondary endpoint of the LANDSCAPE study. Eligible pts had HER2+ MBC with BM not previously treated with WBR, C or L. Pts received L1250 mg/day and C2000 mg/m2/day, days 1–14, every 21 days. The primary endpoint was a centrally assessed CNS objective response (CNS-OR) defined as a ≥50% volumetric reduction of CNS lesions in the absence of increasing steroid use, progressive neurologic symptoms or progressive extra-CNS disease. CTC were detected in 7.5 ml of blood using the CellSearchSystem™, combining EpCAM immunomagnetic selection (IMS) followed by anti-cytokeratin (A45B/B3) fluorescently staining for CTC at baseline and at day (D) 21, before cycle 2. Results: From 04/2009 to 08/2010, 45 pts were enrolled, 41 were evaluable for CTC at baseline and 38 at D21. Median age was 56 (range 35 to 79). PS was >1 only in 2 pts. At baseline, 20/41 (48.8%) pts had ≥ 1CTC and 9 (22%) ≥ 5CTC (range 1–301, median 3). CTC were detected in pts with (18/37) or without disease outside SNC (2/6) (p=0.63). At a median follow-up of 10 months (range 2.9−16.5), median TTP was 6.0 months [95% CI 4.9; 7.4] vs. 4.3 [2.8; 5.9] months for pts without and with CTC at baseline respectively (p=0.14). After 21 days of treatment, a disappearance of CTC was observed in 11pts (31%). At D21, only 7 (18.4%) pts had ≥ 1CTC and 3 (8%) ≥ 5 CTC (p=0.006, D21 vs. baseline). In 43 evaluable pts, CNS-OR rate was 67% (95%CI 51–81), with a median time from inclusion to response of 1.8 month. Absence of CTC was not correlated with CNS-OR rate at baseline (17/21 (81%) vs. 11/19 (58%), NS). Strikingly, remaining positivity for CTC at D 21 (≥ 1CTC) was correlated with a poor response rate in CNS: 2/6 (33.3%) vs. 25/31 (80.6%) in pts with 0 CTC, p=0.03. Conclusions: Early decrease (at D 21) in CTC level is correlated with a high response rate in newly diagnosed BM to L + C and underlines the predictive value of this blood marker in MBC pts even for brain metastasis. Longer follow-up is needed to assess its prognostic value under antiHER2 targeted therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-12.

Background: Resistance to hormonal therapy may be associated with activation of the PI3K/AKT pathway. Preclinically, everolimus (RAD), an oral inhibitor of mTOR, has been shown to reverse resistance to tamoxifen (TAM). In a prior randomized phase II trial in estrogen-receptor positive operable breast cancer pts, RAD significantly increased neoadjuvant AI (letrozole) efficacy when given in combination. The objective of this randomized phase II study was to estimate the efficacy of the RAD+TAM combination in AI pretreated hormone-receptor positive/HER2 negative MBC pts based on the assumption that prior exposure to an AI might potentially enrich the proportion of pts whose tumor may be driven by an activation of the PI3K/AKT/mTOR pathway. Methods: Eligible patients were stratified by time to progression after prior AI treatment and randomized 1:1 to receive either TAM (20mg/day) alone or RAD+TAM (RAD: 10 mg/d; TAM: 20mg/d). The primary objective was to estimate clinical benefit rate (CB) defined as the absence of progression at 6 months in the RAD+TAM arm. Using a Simon two-stage Minimax design, with alpha=5% and power=90%, considering a gain in CB of 20% as the minimum needed to warrant further study for the combination and assuming a CB of 50% in the TAM arm, 53 evaluable patients were needed in both arms. Secondary endpoints included safety and time to progression (TTP). Results: In total, 111 pts (TAM: 57, RAD+TAM: 54) were randomized. Baseline characteristics were well balanced between the two treatment arms; median age was 64 years (range, 41-86); most pts were PS 0 (55 pts, 51%) or PS 1 (46 pts, 43%) Prior AI treatment had been given to 34 pts (31%) in the adjuvant setting; to 67 pts (60%) in the metastatic setting and 10 pts (9%) in both the adjuvant and metastatic setting. This population was poorly hormone sensitive as all but 10 pts (9%) had progressed either during AI or within 6 months after adjuvant AI. Furthermore, 57 pts (51%) and 28 pts (25%) had received prior chemotherapy in the adjuvant and/or metastatic setting, respectively. Efficacy: In an intent-to-treat analysis with a median follow-up of 13 months, CB was 42.1% (95% CI, 29.1-55.9) in the TAM arm and 61.1% (95% CI, 46.9-74.1) in the RAD+TAM arm. Median TTP was 4.5 months (95% CI, 3.7-8.7) with TAM and 8.5 months (95% CI, 6.01-13.9) with RAD+TAM (log-rank test: p=0.008, exploratory analysis). At the time of analysis, 17 pts had died in the TAM arm and 5 patients had died in the RAD+TAM arm (there was no toxic death). Safety: Safety data showed that toxicity was manageable in both groups. RAD had to be decreased to 5 mg/day for 15 pts (28%); 3 and 2 pts had to stop the treatment due to toxicities in the TAM and RAD+TAM arms respectively. Severe adverse events (G3-4) >10% were stomatitis (0/11%, TAM/RAD+TAM) and pain (19%/7%). Conclusions: RAD combined with tamoxifen provides significant improvement in the 6 months clinical benefit rate compared to tamoxifen alone. Based on these promising results, this combination warrants further study in hormone-receptor positive/HER2 negative MBC after progression on AI. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S1-6.

Background: Although the coexistence of osteoarthritis and osteoporosis is considered as uncommon, it has been suggested that, in postmenopausal women, disc space narrowing increases the risk of vertebral fracture. The aim of this study was to check this hypothesis in postmenopausal women with osteoporosis. Objective: We analysed the relationship between vertebral fractures and spine osteoarthritis in 410 postmenopausal women with osteoporosis: in this population both disc space narrowing and osteophytes are inversely related to vertebral fractures. Patients and methods: This study is based on baseline data collected in a multicentre, prospective and 6-month longitudinal observational study. 410 postmenopausal women (74±5 years) were enrolled who had consulted for back pain, and had osteoporosis (according to WHO definition). Spine x -rays were performed according to standardised procedures. Vertebral fractures were evaluated from T4 to L4 using the Genant’s semiquantitative method; osteoarthritis was evaluated by scoring osteophytes and disc space narrowing at all levels of the thoracic and lumbar spine, and by a qualitative assessment of facet joint arthritis. Results: The prevalence of vertebral fractures was 52.4%. At least one osteophyte, one disc space narrowing and one facet arthritis were present in 90.2, 64.6 and 77.8% of patients respectively. There was an inverse association between vertebral fractures and osteoarthritis: odds ratios adjusted for age and weight (95% CI) were 0.38 (0.17–0.86), p = 0.02 and 0.27 (0.16–0.46), p −4 for the presence of at least one osteophyte, and of at least three disc space narrowings respectively. In a cluster analysis, it was possible to identify a subgroup of patients without any disc space narrowing, and another subgroup with all patients having at least one disc space narrowing; the proportion of patients having more than three vertebral fractures was 25.2 and 15.9% in these two clusters respectively. Conclusions: Disc space narrowing and osteophytes are associated with a decreased vertebral fracture prevalence in postmenopausal women with osteoporosis.

Background Few targeted therapies (TTs) are registered for sarcoma treatment despite numerous phase II studies and yet there are potential treatment options for patients after standard treatment escape. The French Sarcoma Group - Bone Tumor Study Group (GSF-GETO) created a national registry to evaluate the outcome of patients treated with off-label TTs. Methods Every consecutive sarcoma-patient receiving an off-label TT outside a clinical trial was included. The objective was to describe this patient efficacy and safety data in routine practice. Results From October 2008 to October 2011, 249 patients in 24 centers received 278 treatment lines with TTs. Twenty-five histological subtypes were included: most frequent were leiomyosarcoma (n = 48, receiving sorafenib in 63%, and sunitinib in 27%), GIST (n = 39, receiving sorafenib in 79%), and angiosarcoma (n =18, receiving sorafenib in 78%). The overall response rate to TTs was 15% (95% CI [10,6-20,2]), the disease control rate at 2 months was 59%. The median progression-free survival was 4,1 months (IC 95% [3,2-4,8]). Three complete responses were observed. No toxic death occurred, grade 3 and 4 toxicities were reported in 74 (27%) and 14 patients (5%) respectively. Conclusion Off-label TTs can be used for sarcoma patients in routine practice with an acceptable toxicity profile and efficacy similar to that reported in non-randomized clinical trials. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-870) contains supplementary material, which is available to authorized users.

Background Everolimus is an agent frequently associated with specific toxicities. Predictive markers of efficacy are needed to help define which patients could benefit from it. The goal of this exploratory study was to identify potential predictive biomarkers in the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activation pathway using primary tumor samples collected during the phase II tamoxifen plus everolimus (TAMRAD) trial. Patients and methods Tumor tissues were collected retrospectively from the TAMRAD trial. Immunohistochemistry was carried out using specific antibodies directed toward proteins that result in mTORC1 activation [canonical phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mTOR or alternative pathways]. DNA was extracted from the tumor tissue; mutation screening in the PIK3CA gene (exons 9 and 20) and the KRAS gene (exons 2 and 3) was first carried out using Sanger direct sequencing, and then completed by next-generation sequencing for PIK3CA. An exploratory analysis of everolimus efficacy in terms of a time-to-progression (TTP) increase was carried out in each biomarker subgroup (high versus low expression referring to the median percentage of marked cells). Results A total of 55 primary tumor samples from the TAMRAD trial—25 from the tamoxifen-alone group and 30 from the tamoxifen/everolimus group—were evaluated for biomarkers. The subgroups most likely to have an improvement in TTP with tamoxifen/everolimus therapy, compared with tamoxifen alone, were patients with high p4EBP1, low 4EBP1, low liver kinase B1, low pAkt, and low PI3K. Among the 45 samples screened for mutation status, nine samples (20%; 95% CI 9.6–34.6) had a PIK3CA mutation. KRAS mutation was observed in one patient. Conclusions A positive correlation between late effectors of mTORC1 activation, a positive correlation between Akt-independent mTORC1 activation, and an inverse correlation between canonical PI3K/Akt/mTOR pathway and everolimus efficacy were observed in this exploratory analysis. However, these correlations need to be validated in larger studies before applying the findings to routine clinical practice.

International audience; BACKGROUND: Having been vaccinated against the human papilloma virus (HPV) may affect other behaviours related to sexual health. This study assessed knowledge and behaviour relevant to the prevention of sexually transmitted infections (STIs) among girls/women aged 14-23 years in relation to their HPV vaccination status. METHODS: From November 2008 to February 2009, 328 girls/women from the Rhône-Alpes region were recruited by general practitioners and completed a self-administered questionnaire. RESULTS: In all, 316 of the 328 respondents provided information on their HPV vaccination status: 135 (42.7%) had been vaccinated (51.2% of girls aged 14-16 years, 44% of women aged 17-20 years and 18.9% of 21-23-year-olds). Knowledge about HPV and the Pap smear was poor overall but greater in those who had been vaccinated: vaccinated 14-16-year-olds were significantly more likely to know the aim of the Pap smear than those not vaccinated (72.7% vs. 41.3%, P < 0.001), and vaccinated 21-23-year-olds were more likely to know about the need to continue Pap smear screening, despite vaccination (60.0% vs. 25.6%, P = 0.06). Irrespective of vaccination status, >80% cited condoms as a means of STI prevention and >85% of those who were sexually active used them. No difference was observed between vaccinated and non-vaccinated groups regarding requests for HIV serology, history of abortions or emergency hormonal contraception. CONCLUSION: Knowledge about cervical cancer prevention was better among those who had been vaccinated against HPV than among those who had not. Knowledge and behaviour relevant to STI prevention seemed appropriate whatever the respondents' vaccination status.

Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. Its effect on relapse and survival is uncertain. Its prognostic value for survival was analyzed in three databases of previously reported prospective multicenter studies: (a) FEC chemotherapy in metastatic breast carcinoma; (b) CYVADIC in advanced soft tissue sarcoma (European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group 62791); and (c) prospective, consecutive phase III studies of aggressive diffuse large-cell non–Hodgkin's lymphomas conducted at Centre Léon Bérard between 1987 and 1993. Univariate and multivariate analyses of prognostic factors for survival were performed. The incidence of lymphopenia of 1, non–Hodgkin's lymphoma patients with international prognostic index (IPI) of > 0, and advanced soft tissue sarcoma and metastatic breast cancer patients with bone metastases. Inunivariate analysis, lymphopenia of

Background: Total and CD4 lymphopenia is observed in 25% of advanced cancers patients and is a predictive factor of chemotherapy (CT)-induced death, febrile neutropenia, thrombocytopenia, anemia, as well as an independent prognostic factor for survival and tumor progression. CYT107 is a glycosylated recombinant human IL-7 (CYTHERIS, France) emerging as a promising immuno-restorative agent well tolerated in Phase 1 trials. To date, it is unknown whether IL-7 can correct lymphopenia during CT and whether this could translate into clinical benefit in advanced cancer patients. Methods: A placebo-controlled, monocentric, Phase 2a (NCT01368107) was conducted in lymphopenic metastatic breast cancer (MBC) patients to be treated by capecitabine (2500mg/m2/d, pers os, 21-day cycle from D21 after randomization). Using a 2x2 factorial design, patients were randomly allocated to 4 arms to receive 1) before the 1st cycle of CT : r-hIL-7 (CYT107:10µg/kg, subcutaneously, weekly at D0, D7, D14, groups 2 & 4) or placebo (groups 1 & 3), then 2) during the 3rd cycle of CT: r-hIL-7 (weekly at D57, D64, D71, groups 3 & 4) or placebo (groups 1 & 2). The primary endpoint, CD4 count evolution, was evaluated before (D0 to D21) and during CT (D57 to D78). Secondary endpoints include risks of severe hematological AE, safety and progression free survival (PFS). An ancillary study has evaluated the quantitative and functional changes in circulating immune cells (see abstract Ménétrier-Caux). Results: From Nov. 2011 to Jun. 2013, 20 patients (median age [range]: 60 [39-76 y.]; median CD4 count on D0: 242 [22-522 cells/µL]) with MBC (mainly with bone and liver metastasis) were enrolled. Before CT (n=20), r-hIL-7 treatment induced a significant increase of CD4 count (median relative evolution: +148.1% [41.8-763.9 cells/µL] in r-hIL-7 groups vs +9.9% [-50.3-102.2 cells/µL] in placebo [Wilcoxon, p=0.002]). During CT (n=11), r-hIL-7 treatment also increased CD4 count (+58.6%[-15.2-281.5 cells/µL] in r-hIL-7 groups vs -2.4% [-27.6-112.5 cells/µL] in placebo [p=0.121]). Overall, r-hIL-7 was well tolerated with reactions related to injection as the main specific AE, no binding or neutralizing antibodies, and no r-hIL-7-related ≥ Grade 3 AE except 1 fatal SAE for which one a relationship to r-hIL-7 cannot be ruled out. Interestingly, r-hIL-7 treatment during CT reduced the incidence of Grade 3 hematological AE compared to placebo (0 vs 5 events, respectively). PFS data will be available by Feb. 2014. Conclusion: In this exploratory trial, r-hIL-7 treatment was safe at biologically active dose, able to correct CD4 lymphopenia and associated with lower incidence of severe hematological toxicity during CT. These early results are encouraging and warrant further investigations of IL-7 clinical applications in the oncology field. Citation Format: Ray-Coquard Isabelle, Olivier Tredan, Gwenaele Garin, Christine Ménétrier-Caux, Sylvie Chabaud, Thomas Bachelot, Claire Cropet, Pierre-Etienne Heudel, Paul Rebattu, Patricia Dupont, Estelle Verronese, Anne-claire Cadore, Valérie Fouillat, Olfa Derbel, Nathalie Bonnin, Thérèse Croughs, Michel Morre, Nicolas Pasqual, Manuari Manuel, Gilles Clapisson, Christophe Caux, David Pérol, Jean-Yves Blay. Elypse-7: A randomized, placebo-controlled, Phase 2a evaluating the impact of IL-7 immunotherapy on CD4 count, risks of severe haematological toxicity and tumor progression in metastatic breast cancer patients. [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 CT333. doi:10.1158/1538-7445.AM2014-CT333

Introduction: We previously showed that T ( Methods: Lymphocytes, NK, monocytes and DC subpopulations quantification and functional competence after reactivation (PMA/ionomycin, TLR7/8-Ligand) were assessed by multiparametric flow-cytometry (surface markers/ intracytoplasmic cytokines) on fresh whole blood (D0, D21, D57, D78, EOS). Impact of CYT107 treatment before (D0-D21) or during (D57-D78) chemotherapy on immune parameters was assessed. Results: At inclusion, 20 patients presented strong quantitative alteration of all lymphocytes subsets compared to a healthy donor women cohort (n=30). Inflammatory monocytes (infl-Mo) and DC subsets were quantitatively reduced. CD4 CD45R0+ T (IFNγ/IL-2), Tγδ cells and NK (IFNγ) cytokine productions were altered independently of quantitative alterations highlighting the importance to assess both. Pre-chemotherapy, CYT107 significantly increased CD3 T cell absolute number (median relative evolution: CYT107+128.5%[39;606cells/µL] vs placebo +1.6%[-34;85cells/µL], p=0.002) involving both CD4 (p=0.002) or CD8 (p=0.006) T cells and naïve (CD4:p=0.005 and CD8:p Conclusion: CYT107 administered before chemotherapy, increases all T cell subsets absolute number but no other compartments without affecting their functional responses. Interestingly, during chemotherapy, CYT107 induces an increase of CD8 memory cells, known to play a role in long lasting defense against tumors. Citation Format: Christine Menetrier-Caux, Isabelle Ray-Coquard, Claire Cropet, Estelle Verronese, Thomas Bachelot, Olivier Tredan, Gwenaelle Garin, Pierre Heudel, Axelle N'Kodia, Ana Delgado, Christine Bardin-Dit-Courageot, Chantal Rigal, Gilles Clapisson, Sylvie Chabaud, David Perol, Paul Rebattu, Thérèse Croughs, Nicolas Pasqual, Manuarii Manuel, Michel Morre, Jean-Yves Blay, Christophe Caux. Interleukin-7 (CYT107) treatment in lymphopenic 1st line metastatic breast carcinoma patients treated with chemotherapy regimen (Capecitabine) favors the restoration of T-cell subsets number. [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 2574. doi:10.1158/1538-7445.AM2014-2574

Aim: GIST is the most common mesenchymal neoplasm of the gastrointestinal tract. In unresectable and metastatic or locally advanced disease, imatinib followed by sunitinib, then regorafenib represent the standard treatments in 1st, 2nd and 3rd line, respectively. Pazopanib is an active treatment in soft tissue sarcomas; it has never been evaluated in a randomized setting in advanced GIST. Methods: Eligible adult patients (pts) with adequate organ functions were randomly assigned (1:1) to receive P + BSC or BSC alone. Randomization was stratified by number of prior drugs (2 vs > = 3). The primary endpoint was Progression-Free Survival (PFS). 80 pts were planned to detect an improvement in the 4-month PFS rate (PFS-4m) from 15% (BSC alone) to 45% (P + BSC) with 5% two-sided a error and 80% power. Secondary objectives included Best Overall Response (BOR), overall survival and safety Results: From Apr 11 to Dec 13, 81 pts were randomized: 40 to P + BSC and 41 to BSC alone. Median age was 63 y (27-85), 70% were males. The intent-to-treat analysis based on investigator-assessed progression showed a significant improvement in PFS with PFS-4m of 47.7% (95% CI 30.9 to 62.7) for P + BSC vs 19.5% (95% CI 9.2 to 32.7) for BSC (HR: 0.56, 95% CI 0.34 to 0.93; stratified log-rank: p = 0.02). 36/41 pts allocated to BSC arm received P following investigator-assessed progression. BOR assessed by central review showed stable disease in 84.2% vs 70.7% and progressive disease in 15.8% vs 26.8% of pts in P + BSC and BSC arms, respectively. 52.5% of pts receiving P + BSC experienced at least one Serious Adverse Event (SAE) vs 14.6% of pts receiving BSC alone. In P + BSC arm, the more frequent SAE were gastrointestinal disorders (n = 7; 17.5%), deterioration of global health status (n = 6; 15%) and pulmonary embolism (n = 5; 12.5%). Conclusions: P combined to BSC improves PFS in pts with advanced GIST resistant to imatinib and sunitinib. Disclosure: J-Y. Blay: Research funding and honoraria from GSK, Novartis, Roche, Pfizer, Bayer; A. Italiano: Research support and honoraria from GSK; P. Cassier: Honoraria from GSK and Servier Travel reimbursment from Novartis, Roche and Servier Research support from Novartis; I.L. Ray-Coquard: Honoraria and research support from GSK & Roche; O. Mir: has acted as a consultant/speaker for Astra-Zeneca, Bayer, GSK, Novartis, Pfizer, Roche and Servier; A. Belleville, J. Gautier and D. Perol: Research support from GSK; A. Le Cesne: Honoraria & Research support from GSK, Pharmamar, Novartis. All other authors have declared no conflicts of interest.

Brain metastases are a devastating event in the progression of cancer and are expected to increase in incidence as chemotherapies improve and lead to better systemic disease control. The brain offers unique environment as it is protected by the blood–brain barrier, which strongly limits the penetration of drugs. Using a quantitative model system for experimental breast cancer brain metastasis, vascular permeability was heterogeneous in brain metastases, with only 10% of lesions exhibiting sufficient permeability to mount an apoptotic response to taxol, suggesting that inadequate chemotherapeutic drug distribution accounts for a lack of efficacy. We have tested 18 compounds, both traditional chemotherapeutics and small molecule inhibitors, for efficacy in an experimental brain metastasis model. Prevention of the development of brain metastases was observed using vorinostat, lapatinib, pazopanib, TPI-287, gemcitabine and irinotecan. No drug effectively shrunk already established metastases. Our work strongly suggests that preventive approaches for the development of brain metastases constitutes a feasible clinical goal. We advocate the use of “secondary brain metastasis prevention” trials, in which patients with limited, treated brain metastases (without whole brain radiotherapy) are randomized to a preventive or placebo, with time to the development of a new metastasis as an endpoint. Close collaboration between researchers and medical oncologists will be needed to address these challenges brought on by this growing and incurable disease. Disclosure B. Gril: Dr. Patricia Steeg received research founding from Glaxo Smith Kline (for lapatinib, pazopanib and PLK inhibitor) and from Millennium Pharmaceuticals (for TAK-285).