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Background Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008. Patients and methods We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2−; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD). Results The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference]. This effect is driven by the HER2+ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference] nor among those with HR+/HER2– MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2– and TNBC cohorts, respectively, whatever YOD. Conclusion OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed., Highlights • OS of HER2+ MBC patients keeps improving over time [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. • This effect seems timely related to the release of drugs demonstrated to improve survival in clinical trials. • OS gains observed in real life among HER2+ MBC patients are at least equivalent to those observed in clinical trials. • YOD had no sustained impact on OS among patients with TNBC and luminal MBC. • The impact of CDK4/6 inhibitors cannot yet be assessed in this cohort.

Background Cancer patients presenting with COVID-19 have a high risk of death. In this work, predictive factors for survival in cancer patients with suspected SARS-COV-2 infection were investigated. Methods PRE-COVID-19 is a retrospective study of all 302 cancer patients presenting to this institute with a suspicion of COVID-19 from March 1st to April 25th 2020. Data were collected using a web-based tool within electronic patient record approved by the Institutional Review Board. Patient characteristics symptoms and survival were collected and compared in SARS-COV-2 real-time or reverse-transcriptase PCR (RT-PCR)–positive and RT-PCR–negative patients. Results Fifty-five of the 302 (18.2%) patients with suspected COVID-19 had detectable SARS-COV-2 with RT-PCR in nasopharyngeal samples. RT-PCR–positive patients were older, had more frequently haematological malignancies, respiratory symptoms and suspected COVID-19 pneumonia of computed tomography (CT) scan. However, respectively, 38% and 20% of SARS-COV-2 RT-PCR–negative patients presented similar respiratory symptoms and CT scan images. Thirty of the 302 (9.9%) patients died during the observation period, including 24 (80%) with advanced disease. At the median follow-up of 25 days after the first symptoms, the death rate in RT-PCR–positive and RT-PCR–negative patients were 21% and 10%, respectively. In both groups, independent risk factors for death were male gender, Karnofsky performance status, Highlights • Cancer patients with SARS-COV-2 real-time or reverse-transcriptase PCR (RT-PCR have a death rate of 20% at 30 days. • Cancer patients with clinical symptoms of COVID-19 but SARS-COV-2 RT-PCR have high death rate. • 70% cancer patients suspected COVID-19 dying before day 30 have no SARS-COV-2 on RT-PCR or computed tomography. • For both groups, the risk factors of death include "relapsing cancer", Karnofsky performance status

Background: This nationwide prospective cohort reports on the outcome of patients with cancer presenting COVID-19 symptoms with or without detectable SARS-COV2 on RT-PCR and/or specific CT-scan imaging. Methods: This prospective study was conducted in 23 Cancer Centers and hospitals. Inclusion criteria were :1) confirmed diagnosis of solid or hematologic cancer in treatment and 2) clinical symptoms of COVID-19. COVID-19 infection was defined as: 1) detectable SARS-CoV2 on RT-PCR (repeated twice if negative first) and/or specific CT-scan imaging if undocumented SARS-COV-2 on RT-PCR. The primary endpoint was death at day-28 after COVID-19 test, in patients with (COVID-19 positive group) or without (COVID-19 negative group) documented COVID-19. Findings: From March 1st 2020 to May 21st 2020, 1230 cancer patients with suspicion of COVID-19, including 1162 (94·5%) matching inclusion criteria were included. 425 (36·6%) [including 155 [13·3%] with diagnosis on CT-scan only], and 737 (63·4%) were in the COVID-19+ and COVID-19- groups respectively. Deaths within 28 days after COVID-19 diagnosis occurred in 116/425 (27·8%) of COVID-19+ patients, and in 118/737 (16·3%) of COVID-19 negative patients (p 100 mg/L vs 35/203 (17·4%) of other patients died before day 28 (p

International audience; BACKGROUND:The International organization for standardization (ISO) is the world leader in providing industrial and commercial standards and certifications. Beyond medical devices, four French clinical research and innovation departments have received an ISO 9001 certification (the standard for quality management). Simultaneously, medico-economic studies have become increasingly important in the public decision process. Using the clinical research and innovation department from the Léon-Bérard Cancer Center as an example, the purpose of this article is to show how the scope of the ISO 9001 certification has been extended to cover medico-economic studies.METHOD:All of the processes, procedures, operating modes, documents, and indicators used by the clinical research and innovation department of the Léon-Bérard center were investigated. Literature searches were conducted using Medline keywords. The recommendations from the French national authority for health and other organizations, such as the International society for pharmacoeconomics and outcomes research (ISPOR), were also considered, as well as the recommendations of the General inspectorate of social affairs.RESULTS:In accordance with the national and international recommendations, two procedures were created and four procedures were revised at this center. Five indicators of quality and an evaluation chart were developed.CONCLUSION:By adopting the ISO 9001 certification into its medico-economic studies, the clinical research and innovation department of the Léon-Bérard center has used an innovative approach in the context of the growing importance of economic studies in decision-making.Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Background Genomic alterations of receptor tyrosine kinases (RTK) or ligands are biomarkers for some targeted therapies in a fraction of cancers, with heterogeneous responses across tumor types. A general model to predict the efficacy of a targeted treatment in a given tumor type bearing a RTK genomic alteration is lacking. Through database and literature review, we investigated whether the role of a RTK in the normal lineage could predict the response to RTK inhibitors in cancers arising from the same lineage. Methods An analysis of the literature and query of public databases on RTK function in normal cell lineages and neoplastic cells was conducted, for 16 selected RTK (EGFR, HER2, KIT, FLT3, TRKA-B-C, ROS1, ALK, RET, MET, and FGFR1-2-3-4). The physiological role of RTK in the development/maintenance of cell lineages was assessed by looking at the phenotypes resulting from the alteration of the RTK in animal models and/or known human germline mutations. The activity of TKI monotherapy in genomic-driven clinical trials was analyzed through a systematic review of published phase I-II-III studies. Efficacy was defined as a median progression-free survival > 6 months and of a response rate > 30%. A matrix was built to test the association between the physiological role and clinical activity of each RTK according to lineage contexts. Results This analysis reveals a relationship between the role in lineage development and the magnitude of clinical activity of a TKI in a cancer arising from the same lineage. For missense mutations only, the clinical activity was higher when the RTK is involved in the development or maintenance of the normal cell lineage. Conversely, in cancers harboring fusion genes and proteins involving an RTK, TKI were active regardless of cell lineage. Single agent TKI activity was consistently limited in cancers bearing RTK gene amplifications. Conclusions This analysis identifies two preferred genomic biomarkers to select candidate patient for single agent TKI, 1) fusions genes involving an RTK; 2) activating missense mutations in RTK involved in normal cell lineage physiology. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure P.A. Cassier: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Research grant / Funding (institution): Blueprint; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Sharp & Dohme; Research grant / Funding (institution): Tayo; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Innate. I.L. Ray-Coquard: Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (institution): Amgen; Honoraria (self), Research grant / Funding (institution): Genmab; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Pfizer. D. Perol: Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): Bristol-Myers Squibb. J-Y. Blay: Research grant / Funding (self): PharmaMar; Research grant / Funding (self): GlaxoSmithKline; Research grant / Funding (self): Novartis; Research grant / Funding (self): Eisai; Research grant / Funding (self): Lilly; Research grant / Funding (self): Merck Sharp and Dohme; Research grant / Funding (self): Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

Background Netrin-1, a dependence receptor ligand, is overexpressed in many cancers and leads to resistance to cell death. In preclinical studies, targeting netrin-1 with the humanized anti-netrin-1 antibody NP137 inhibits tumor growth and metastasis. Methods Adults with advanced, refractory solid tumors received NP137 IV Q2W, starting at 1 mg/kg. Dose was escalated using a rapid titration design followed by a model-based design with 3-6 pts per cohort; Additional patients (pts) were enrolled in 4 biomarker cohorts, at dose levels that had been declared safe, starting at 6 mg/kg, and underwent paired biopsies for pharmacodynamics (PD) purposes. Results Nineteen pts were enrolled in 7 dose levels (1 to 20 mg/kg). No DLTs were observed but 11 (58%) had infusion related reactions (IRR) of grade 1-2 severity, all at doses of 4 mg/kg and above. Twenty-three pts were enrolled in the biomarker cohorts (up to 6 pts per cohort), and 18 (78%) experienced IRR. To date, 9 of 42 pts (21%) experienced at least one grade ≥ 3 drug related AE and 9 pts had at least one related SAEs (total of 14 SAEs including 10 IRRs and ischemic stroke, back pain, hyponatremia, pneumonia, n = 1 each). Among 36 pts with at least one follow-up RECIST 1.1 assessment, 1 pt with endometrial carcinoma had a confirmed PR (> 6 months to date, >50%, 14mg/kg) and 6 pts had SD at 3 months including one long-lasting SD over 1 year (cervical carcinoma, 6mg/kg) with a shrinkage > 30% in an irradiated lesion. To date, 3 pts are still on treatment (median duration: 43.0 days [7.0; 476.0]). Serum NP137 concentrations had biphasic disposition characteristic of both target and non-target-mediated clearances. PK data up to 5 consecutive cycles showed no evidence of NP137 accumulation. No ADAs were noted. RNAseq data on paired biopsies suggests that NP137 triggers a shift toward a more epithelial phenotype. Based on available data, 14mg/kg Q2W was selected as the RP2D. Recruitment in the extension phase is ongoing in gynecological tumors. Conclusions NP137 was well-tolerated, with mild to moderate IRR as the most frequent treatment-related AEs and showed encouraging signs of clinical activity. Updated data will be presented at the meeting. Clinical trial identification NCT02977195. Legal entity responsible for the study Centre Leon Berard. Funding Netris Pharma. Disclosure P. Cassier: Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Abbvie; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. Y. Courbebaisse: Full / Part-time employment: Netris Pharma. S. Depil: Advisory / Consultancy: Cellectis; Advisory / Consultancy: Netris Pharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: PDCLine Pharma; Advisory / Consultancy: Erytech; Advisory / Consultancy: Servier. J. Delord: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Roche/Genentech; Advisory / Consultancy: EMD Serono; Research grant / Funding (self): AstraZeneca. I.L. Ray-Coquard: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astr-Zeneca; Honoraria (self), Advisory / Consultancy: Clovis; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: GenMab. B. Ducarouge: Full / Part-time employment: Netris Pharma. P. Mehlen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netris Pharma. J. Blay: Non-remunerated activity/ies, uncompensated scientific advice: Netris Pharma. All other authors have declared no conflicts of interest.

Background The PI3K/AKT pathway activation is an independent marker of poor outcome in head and neck squamous-cell carcinoma (HNSCC). It is involved in resistance to cetuximab and PI3KCA mutations (5% of HNSCC) may be a key event of this dysregulation. Buparlisib is an oral, pan-Class I PI3K inhibitor that inhibits tumor growth in HNSCC xenografts. Methods This phase II evaluated the efficacy of oral buparlisib (100mg/d) in 2 parallel cohorts of refractory HNSCC (progression after platinum and cetuximab) with (PIK3CAmutated, exons 9/20) or without (PIK3CAnon-mutated) PI3KCA activating mutation. The primary endpoint was 2-month Disease Control Rate (DCR2m) as per centrally reviewed RECIST 1.1. Secondary endpoints included ORR, PFS, OS, and safety. Buparlisib would be considered ineffective if DCR2m ≤ 10% and promising if ≥ 30% (Simon’s optimal two-stage design; α: 5% unilateral, power: 90%): 7 successes/35 evaluable patients per cohort were required. Results 58 HNSCC heavily pre-treated (78% at least 2 prior lines) received at least one dose of buparlisib (PIK3CAnon-mutated, n = 36 and PIK3CAmutated, n = 22) The PIK3CAmutated cohort was prematurely closed because of slow accrual). The DCR2m was 38.9% (95% CI [25.5; + ∞[) for PIK3CAnon-mutated and 36.4% (95% CI [19.5; + ∞[) for PIK3CAmutated. No objective response was observed. Median PFS was 1.8 m (95% CI [1.6; 3.5]) and 1.7 m (95% CI [1.1; 4.1]) for PIK3CAnon-mutated and PIK3CAmutated respectively. Median OS was 5.8 m (95% CI [3.7; 9.2]) and 3.4 m (95% CI [2.6; 7.9]) for PIK3CAnon-mutated and PIK3CAmutated. Most common related AEs (>25%) included hyperglycemia, asthenia, anxiety, depression, lymphopenia, anemia, leucocyte increase, hematocrite decrease, Na decrease, nausea and diarrhea. Most frequent related AE ≥ Grade 3 (>5%) were hyperglycemia, lymphopenia, asthenia, Na decrease, depression, dermatitis. 14 pts (24.1%) discontinued buparlisib due to an AE. Conclusions Buparlisib had limited antitumor activity in heavily pre-treated HNSCC patients independent of PI3KCA mutational status. Clinical trial identification NCT01737450. Legal entity responsible for the study Centre Leon Berard. Funding INCA et Fondation ARC. Disclosure J. Fayette: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Honoraria (self): Merck Serono; Advisory / Consultancy: innate pharma; Advisory / Consultancy: Biogen. A. Daste: Honoraria (self), Advisory / Consultancy: BMS. C. Even: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Merck Serono. F. Peyrade: Honoraria (self): BMS; Honoraria (self): Merck Serono. C. Le Tourneau: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: AstraZeneca.

Background We previously demonstrated that interruption of imatinib mesylate (IM) in responding patients (pts) with advanced gastrointestinal stromal tumours (GISTs) results in rapid reprogression. The impact of interruption on residual tumour, quality of response and secondary resistance has not been fully investigated. Patients and methods Within the BRF14 study, 71 non-progressing patients were randomly assigned in the interruption arms after 1, 3 or 5 years. IM was resumed in the case of progressive disease (PD). Tumour status at randomisation, relapse and after IM rechallenge, progression-free survival (PFS) and time to secondary resistance were analysed. Results At data cut-off, 51 of 71 patients had restarted IM following documented PD. Eighteen patients (35%) progressed on known lesions only, while 33 patients (65%) had new lesions, with concomitant progression of known lesions in 17 patients. Only 8 (42%) of complete remission (CR) patients and 12 (52%) of partial response (PR) patients at randomisation achieved a new CR and PR. Patients progressing rapidly after interruption had a poorer prognosis. Tumour status at randomisation influenced time to progression after rechallenge. Conclusion In advanced GIST patients interrupting IM, quality of response upon reintroduction did not reach the tumour status observed at randomisation. Rapid progression after imatinib interruption is associated with poor PFS after reintroduction.

Background Bevacizumab combined with paclitaxel as first-line chemotherapy for patients with HER2-negative metastatic breast cancer (MBC) has led to mixed results in randomized trials, with an improvement in progression-free survival (PFS) but no statistically significant overall survival (OS) benefit. Real-life data could help in assessing the value of this combination. Patients and methods This study aimed to describe the outcome following first-line paclitaxel with or without bevacizumab in the French Epidemiological Strategy and Medical Economics (ESME) database of MBC patients, established in 2014 by Unicancer. The primary and secondary end points were OS and PFS, respectively. Results From 2008 to 2013, 14 014 MBC patient files were identified, including 10 605 patients with a HER2-negative status. Of these, 3426 received paclitaxel and bevacizumab (2127) or paclitaxel (1299) as first-line chemotherapy. OS adjusted for major prognostic factors was significantly longer in the paclitaxel and bevacizumab group compared with paclitaxel [hazard ratio (HR) 0.672, 95% confidence interval (CI) 0.601–0.752; median survival time 27.7 versus 19.8 months]. Results were consistent in all supportive analyses (using a propensity score for adjustment and as a matching factor for nested case–control analyses) and sensitivity analyses. Similar results were observed for the adjusted PFS, favoring the combination (HR 0.739, 95% CI 0.672–0.813; 8.1 versus 6.4 months). Conclusions In this large-scale, real-life setting, patients with HER2-negative MBC who received paclitaxel plus bevacizumab as first-line chemotherapy had a significantly better OS and PFS than those receiving paclitaxel. Despite robust methodology, real-life data are exposed to important potential biases, and therefore, results need to be treated with caution. Our data cannot therefore support extension of current use of bevacizumab in MBC.

International audience; Monitoring functional competence of immune cell populations in clinical routine represents a major challenge. We developed a whole-blood assay to monitor functional competence of peripheral innate immune cells including NK cells, dendritic and monocyte cell subsets through their ability to produce specific cytokines after short-term stimulation, detected through intra-cytoplasmic staining and multi-parametric flow-cytometry. A PMA/ionomycin T cell activation assay complemented this analysis. Comparing cohorts of healthy women and breast cancer (BC) patients at different stages, we identified significant functional alteration of circulating immune cells during BC progression prior to initiation of treatment. Of upmost importance, as early as the localized primary tumor (PT) stage, we observed functional alterations in several innate immune populations and T cells i.e. (i) reduced TNFalpha production by BDCA-1+ DC and non-classical monocytes in response to Type-I IFN, (ii) a strong drop in IFNgamma production by NK cells in response to either Type-I IFN or TLR7/8 ligand, and (iii) a coordinated impairment of cytokine (IL-2, IFNgamma, IL-21) production by T cell subpopulations. Overall, these alterations are further accentuated according to the stage of the disease in first-line metastatic patients. Finally, whereas we did not detect functional modification of DC subsets in response to TLR7/8 ligand, we highlighted increased IL-12p40 production by monocytes specifically at first relapse (FR). Our results reinforce the importance of monitoring both innate and adaptive immunity to better evaluate dysfunctions in cancer patients and suggest that our whole-blood assay will be useful to monitor response to treatment, particularly for immunotherapeutic strategies

Objectif de l’etude Des taux heterogenes de recidive locale sont observes chez des patientes atteintes de cancers du sein avec des facteurs pronostiques similaires. Une des hypotheses expliquant ces recidives locales est que certains cancers sont initialement radioresistants. L’objectif de cette etude etait d’identifier des biomarqueurs genetiques de radioresistance du cancer du sein. Materiel et methode Le profil genetique tumoral de 162 patientes inclus dans l’essai ProfiLER (NCT01774409) entre 2013 et 2016 a ete determine par sequencage haut debit et puce d’hybridation genomique comparative. L’association entre les alterations genetiques (mutations, amplifications, deletions) et les caracteristiques des patients a ete analysee. Seules les alterations genetiques presentes dans plus de 3 % des tumeurs ont ete prises en compte. Tous les patients avaient beneficie d’une radiotherapie locale. Resultats Un total de 218 alterations genetiques a ete mis en evidence, dont 18 retrouvees dans plus de 3 % des tumeurs. Une seule alteration genetique etait correlee statistiquement avec le risque de recidive locale. Les patientes atteintes d’une tumeur avec une mutation de PIK3CA (n = 34, 21 %) avaient une duree mediane de survie sans progression locale de 19,8 ans, contre 9,1 ans pour les patientes atteintes de tumeur sans mutation (hazard ratio [HR] : 0,29 ; intervalle de confiance a 95 % [IC95 %] : 0,13–0,64 ; p = 0,002 en analyse unifactorielle). La mutation de PIK3CA a ete identifiee comme etant un facteur protecteur independant de recidive locale en analyse multifactorielle (HR : 0,27 ; IC95 % : 0,09–0,82 ; p = 0,02). Par ailleurs, les patientes atteintes d’une tumeur avec une mutation de ROS1 (n = 8, 4,9 %) avaient une duree mediane de survie sans progression locale de 4 ans, contre 16,1 ans pour les patients atteintes de tumeur non mutee (HR : 2,5 ; IC95 % : 1,74–7,05 ; p = 0,08). Conclusion La mutation de PIK3CA etait associee avec un risque plus faible de recidive locale, dans cette population de patients traites pour des cancers du sein. Ces resultats sont en accord avec des donnees precliniques recentes suggerant que PIK3CA a un impact sur la radiosensibilite.

Purpose. The primary objective of this study was to compare the levels of environmental contamination before and after the introduction of PhaSeal® (closed-system drug transfer device) in two hospital pharmacies. Our secondary objective was to assess the impact of the device on the duration of drug preparation compared to procedures involving the use of needles and syringes. Methods. The study involved two French hospitals, which prepared antineoplastic chemotherapy using a biological safety cabinet and an isolator. Five skilled pharmacy technicians at each hospital prepared a total of 100 chemotherapy preparations using the standard procedure and 100 using the PhaSeal® system. To control for possible contamination occurring in the course of the procedure, we used fluorescein which becomes fluorescent when exposed to UV light. To reply the second objective, we timed the duration of the different steps of the manipulation. Results. Our findings showed a major reduction in the contamination of the work environment when using the PhaSeal® system for drug preparation. Reduction rates higher than 93% were obtained, whatever the type of protection used. On the duration of preparation, our results indicate that this duration would be approximately 1 h longer for the preparation of 100 samples. Conclusion. In conclusion, this study clearly establishes the benefit of using PhaSeal® for protecting the staff members who work with hazardous agents. It also indicates that the duration of drug preparation is not impacted by the use of the system.

Background: Imatinib induces responses and disease stabilisations in non-resectable patients with aggressive fibromatosis (AF). The precise target of imatinib in AF and predictive factors for response to treatment are unknown. Methods: We investigated factors potentially predictive of response to imatinib in a series of 40 patients with progressive AF included in a phase II trial of imatinib: we tested the presence of KIT exon 10 variant (M541L), the expression of imatinib-sensitive kinases and cell cycle proteins by immunohistochemistry (IHC), and other clinical and biological factors. Results: Of 10 patients for whom DNA could be extracted, 3 had a KIT exon 10 variant (30%), with no correlation with response or progression-free survival (PFS). The expression of other imatinib targets (PDGFRA/B, macrophage colony-stimulating factor receptor (M-CSFR)) and of downstream components of the cell cycle, cell proliferation and proliferation pathway (cyclin D1, ERK, MEK 1–2) did not correlate with PFS. Pre-treatment lymphopenia (120 mm correlated with shorter PFS in univariate and multivariate analyses. Conclusion: Our findings show that a baseline biological characteristic of the patient is the major parameter influencing response to imatinib in aggressive fibromatosis. Tumour characteristics, including the presence of a KIT exon 10 M541L variant, may influence tumour control but this needs to be confirmed and better explained.

Resume But de l’etude Le serome est la complication mineure la plus frequente apres une reconstruction mammaire par lambeau de grand dorsal. Il entraine une gene pour la patiente et des consultations iteratives pour ponctions. Le meilleur moyen de le traiter est sa prevention. Pour obliterer l’espace mort dans lequel le serome peut se former, nous capitonnons le site donneur par la technique de capitonnage ou quilting suture , inspiree du designer Chippendale. Le but de cette etude retrospective est d’evaluer l’efficacite et la tolerance de cette technique sur une serie homogene de 200 reconstructions mammaires par lambeau de grand dorsal sans prothese realisees entre 2004 et 2007 par le meme operateur et selon la meme technique. La moitie des patientes a beneficie du capitonnage dorsal et l’autre moitie n’en a pas beneficie. Patientes et methodes Les deux groupes ont ete compares en prenant en compte l’âge, l’indice de masse corporelle (IMC), le tabagisme, les complications postoperatoires, le nombre de ponctions, le temps de drainage, ainsi que les douleurs dorsales postoperatoires. Pour etre efficace, le capitonnage necessite la repartition d’au moins 12 points sous le lambeau cutane inferieur et six sous le lambeau superieur, ainsi que sous la ligne de suture, ce qui prend 15 minutes. La tension cutanee est repartie au fur et a mesure sur l’ensemble des points en abaissant l’epaule de la patiente, diminuant ainsi les tractions sur la suture finale. Resultats L’efficacite du capitonnage depend du nombre de points realises. Cette technique permet l’ablation des drains de Redon a j6 en diminuant de moitie le taux de serome dorsal prolonge, evitant ainsi des ponctions aux patientes. En diminuant les tractions sur la suture cutanee, les retards de cicatrisation dorsale sont aussi reduits. Conclusion La technique de capitonnage type « Chippendale » est efficace contre les seromes prolonges, economique et de realisation rapide. Cet artifice technique simplifie ainsi les suites operatoires du lambeau de grand dorsal sans prothese dont le serome etait le principal inconvenient.

Resume But de l'etude Le but de ce travail est d'etudier les avantages, inconvenients et resultats de la reconstruction mammaire bilaterale sequentielle par lambeau myocutaneograisseux de grand dorsal. Materiel et methode Cette etude retrospective porte sur une serie de 31 reconstructions mammaires bilaterales sequentielles consecutives realisees par le meme operateur entre 1993 et 2001. Ces reconstructions etaient realisees, de facon differee ou immediate, apres mastectomie radicale modifiee ou avec conservation de l'etui cutane pour neoplasie mammaire primitive. La technique chirurgicale utilisee etait le lambeau myocutaneograisseux pedicule de grand dorsal. La reconstruction du sein controlateral etait toujours differee de quelques mois afin de limiter les complications dorsales. L'etude a pris en compte les donnees preoperatoires, les complications postoperatoires, la survenue d'un lymphocele dorsal, la qualite des resultats morphologiques, la satisfaction des patientes avec un recul moyen de 22 mois. Resultats Les resultats confirment que la technique est fiable. Il n'existe pas de difference significative dans les taux de complications postoperatoires ou de survenue d'un lymphocele dorsal entre la reconstruction du premier sein et celle du sein controlateral. Les sequelles fonctionnelles du prelevement bilateral des muscles grands dorsaux sont moderees. Le taux de satisfaction des patientes est eleve (tres satisfaites : 90,3 %, satisfaites : 6,5 %, moyennement satisfaites : 3,2 %) et les resultats morphologiques sont encourageants (tres bons resultats : 84 %, bons resultats : 16 %). Conclusion Le lambeau myocutaneograisseux pedicule de grand dorsal permet une reconstruction mammaire bilaterale autologue sequentielle. Son principal inconvenient est l'impossibilite de realiser une reconstruction mammaire bilaterale simultanee. Il s'agit donc pour nous d'une excellente alternative dans toutes les indications de reconstructions mammaires decalees.

Resume Des protocoles de depistage et de prise en charge nutritionnelle pediatrique dans le cadre du Plan national nutrition sante ont ete proposes mais ne sont pas specifiques a l'oncologie. Ainsi, le score de risque nutritionnel pediatrique (SNRP) classe tous les enfants cancereux a haut risque de denutrition, or une prise en charge nutritionnelle systematique n'est pas toujours possible dans le contexte actuel. But. – Determiner la prevalence de la denutrition et les facteurs predictifs d'une perte de poids (PdP) majeure (PdPM) pendant le traitement definit si PdP superieure ou egale a 5 % en 1 mois, superieure ou egale a 7,5 % en 3 mois, superieure ou egale a 10 % en 6 mois. Methodes. – Une etude retrospective realisee en 2002 dans un service d'oncologie pediatrique a permis d'analyser les poids (P), taille (T), SRNP, score fonctionnel de Lansky et type de cancer recueillis au moment du diagnostic (t0) ainsi que les P, T et la PdPM notes a chaque cure de chimiotherapie ou hospitalisation. La denutrition a t0 etait definie selon les rapports P/T. La relation entre la survenue d'une PdPM et les facteurs recueillis a ete testee par regression logistique. Resultats. – Parmi les 70 enfants inclus, 16 (22,9 %) etaient denutris a l'admission. Pendant le traitement 29 (41,4 %) enfants avaient une PdPM. Les enfants moderement ou legerement denutris a t0 avaient un odds ratio de PdPM augmente de maniere non significative par rapport aux enfants avec un statut nutritionnel normal. On a identifie des cancers a haut risque de denutrition : tumeurs d'Ewing, lymphomes B, tumeurs ORL, osteosarcomes, cancers metastatiques ou traites par chimiotherapie avec greffe de cellules souches, soit 29 enfants (41,4 %) qui ont un odds ratio de PdPM de 5,9 [IC95 % 2,0–16,7]. Conclusion. – Tenir compte, en plus du SRNP, d'autres facteurs de risque permettent de depister des enfants a haut risque de PdPM et de proposer une prise en charge nutritionnelle plus precoce et personnalisee.

Neuroblastoma, the most common extracranial solid tumour in children, is characterised by highly heterogeneous clinical behaviour; patients are stratified into risk categories according to a combination of clinical and biological markers. However, identifying non-invasive prognostic markers predicting outcome independently from current risk-stratification features remains critical for better disease monitoring. Using the SELDI-TOF-MS technology (surface-enhanced laser desorption/ionization time-of-flight mass spectrometry), we found a serum biomarker that strongly correlates with prognosis in neuroblastoma patients. Subsequent peptide mapping identified this biomarker as SAA protein. In support of this observation, high SAA levels were detected by ELISA in the sera of patients with poor prognosis neuroblastoma. Based on this finding, promises and limitations of the approach are discussed.

International audience; BACKGROUND: Imatinib is the standard of care for patients with advanced gastrointestinal stromal tumors (GIST). DESIGN: This article reviews recent data on the impact of imatinib treatment interruption and subsequent rechallenge in patients with advanced GIST. RESULTS: The randomized BFR14 trial showed that (i) interruption of imatinib after 1, 3, or 5 years of treatment in patients with nonprogressive GIST was associated with a high risk of progression even in patients with a complete response; (ii) rechallenge with imatinib restored tumor control in most patients, but the tumor response seldom reached that before treatment interruption; (iii) patients receiving continuous imatinib had a high rate of prolonged tumor control, which increased with longer imatinib treatment. The findings in the metastatic setting have important implications regarding the duration of adjuvant imatinib in GIST. CONCLUSIONS: Discontinuation of imatinib in responding patients with advanced GIST is associated with a high risk of progression and is therefore not recommended. Although rechallenge is a strategy for treating patients who relapse after stopping imatinib, suboptimal tumor response indicates that continuous kinase suppression is necessary to achieve the best clinical outcome. Three-year adjuvant imatinib is recommended for patients with resected 'high-risk' GIST; however, a longer duration may provide additional benefits.

Seroma is the most frequent minor complication after harvesting latissimus dorsi flap for breast reconstruction. It induces patient's discomfort and multiple consultations for punctions. The dead space resulting from the harvest has to be closed by the "quilting suture" in order to prevent the seroma. Our aim is to evaluate the efficiency and the tolerance of the quilting suture by comparing two groups of 100 patients who had a breast reconstruction by the same technic of extended latissimus dorsi flap, performed by the same surgeon, from 2004 to 2007. Half of patients had the classic way of dorsal closure, and the other half of patients had the dorsal quilting suture.In order to compare the two groups we have collected data concerning age, body mass index (BMI), tobacco use, postoperative complications, number and volume of punctions, draining time and postoperative pain. The efficiency of the quilting suture lies on a rigorous repartition of at least six sutures on the upper skin flap, 12 on the lower skin flap and under the skin suture line. The suture model is based on the one used for the Chippendale-designed sofa. We suture the skin flap while pushing down the shoulder, in order to split the skin tension and avoid traction on the final skin suture line. The procedure takes 15 minutes.The "Chippendale" technic allows to reduce draining time from 12 days to 6 days. The incidence of chronic seroma is reduced by 50%. The dorsal wound healing seems also better thanks to tension reduction resulting from the quilting suture.The "Chippendale" technic is a quick, cheap and easy learned procedure, efficient for preventing chronic seroma after the latissimus dorsi flap. The postoperative recovery is eased and the patients comforted.