tbuckley/cabot-search huggingface dataset:
Azacitidine (AZA) Prolongs Overall Survival in Older Patients with Acute Myeloid Leukemia (AML) with Poor Prognostic Karyotypes Compared with Conventional Care Regimens (CCR)
Authors: Hartmut Döhner, Paresh Vyas, John F. Seymour, Valeria Santini, Richard M. Stone, Mark D. Minden, Haifa Kathrin Al-Ali, Teresa Bernal del Castillo, John Morrill, Stephen Songer, Jerry Weaver, Barry S. Skikne, C.L. Beach, Hervé Dombret
Journal: Blood (2016)
Phase Ib study of PF-04136309 (an oral CCR2 inhibitor) in combination with nab-paclitaxel/gemcitabine in first-line treatment of metastatic pancreatic adenocarcinoma
Authors: M. Noel, M. Lowery, D. Ryan, B. Wolpin, A. Bullock, C. Britten, B. Jin, B.J. Ganguly, C.T. Taylor, D. Yin, D.A. Wunderlich, E.C. Gamelin, D.C. Linehan
Journal: Annals of Oncology (2017)
CD44 modulates cofilin expression in human colon cancer cells
Authors: Venkateswaran Subramaniam, Isabella R. Vincent, Emily Chan, Serge Jothy
Journal: Cancer Research (2006)

3442  Colon cancer is among the leading causes of cancer death in North America. Dysregulation of the colonic crypt homeostasis is evident in the early stage of cancer. Moreover, cytoskeletal rearrangement of actin also plays a crucial role in morphological changes during neoplastic transformation events, including impairment of apoptosis. CD44, an adhesion and antiapoptotic molecule is overexpressed in colon cancer and is known to interact with certain cytoskeletal proteins. Cofilin is an actin binding protein and is involved with the directional motility of cells. In the present study, we asked whether the upregulation of CD44, has an effect of cofilin and proteins acting downstream from them. We used a human colon cancer cell line, HT29, which expresses both the standard and variant isoforms of CD44, HT29 where CD44 expression was inhibited by siRNA, and the colon from CD44 knockout and control mice. Western blot analysis of lysates from HT29 cells where CD44 levels were downregulated by siRNA, showed increased level of cofilin expression compared to vector control. The same set of lysates also had increased level of AKT phosphorylation. Immunocytochemistry showed that cofilin expression in colonic epithelial cells was greater in HT29 cells where CD44 was inhibited by siRNA, as compared to vector controls. Experiments using LY294002, an inhibitor of AKT phosphorylation, indicated that cofilin is stabilized by phosphorylated AKT. Knockout mice colon and colonic crypts isolated from them exhibit greater levels of active caspase 3, as compared to wild type mice. Western blot analysis of CD44 knock out mice colon lysates exhibited slightly lower levels of cofilin as compared to the colon lysates from wild type mice. This is in spite of having higher levels of AKT phosphorylation suggesting that other compensatory pathways operate in vivo. Cofilin expression is thus mechanistically associated with CD44 expression. AKT-phosphorylation and caspase 3 activation may have a key role in cofilin modulation. Given the well defined roles of CD44, phosphorylated AKT and caspase 3 in apoptosis and cancer, their role in modulating cofilin expression can cause alterations in the directional motility of tumor cells.
Infecção meningocócica na Escócia, de 1995 a 1997
Authors: S. J. O’Brien, L. E. Smart
Journal: Eurosurveillance (1997)

A incidencia da infeccao meningococica na Escocia foi de 4,1 casos por 100 000 habitantes em 1996 comparada com 3.8/100 000 em 1995 (210 casos notificados em 1996 comparados com 193 em 1995). Houve 14 mortes, o que representou uma taxa de letalidade bruta de 6.7%, que virtualmente nao diferiu da de 1995. A taxa de letalidade associada a septicemia meningococica foi, no minimo, dupla da associada a meningite meningococica isolada (1).
Chemoradiotherapy versus radiotherapy in the treatment of salivary glands and nasal tumors: The GORTEC 2016-02 study
Authors: F.R. Ferrand, J. Thariat, N. Vulquin, V. Calugaru, O. Malard, C. Murariu, F. Janot, F. Louat, C. Michel, J. Bourhis
Journal: Annals of Oncology (2017)
FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer: A subset analysis from the nation-wide multicenter observational study (JASPAC06)
Authors: N. Kobayashi, K. Omae, Y. Horita, H. Ueno, N. Mizuno, K. Uesugi, K. Sudo, M. Ozaka, H. Hayashi, N. Okano, K. Kamei, A. Yamaguchi, S. Kobayashi, S. Suzuki, S. Ishihara, T. Uchiyama, A. Todaka, A. Fukutomi
Journal: Annals of Oncology (2017)
Wine and Cardiovascular Health
Authors: Sohaib Haseeb, Bryce Alexander, Adrian Baranchuk
Journal: Circulation (2017)

Alcoholic beverages have been consumed for thousands of years, attracting great human interest for social, personal, and religious occasions. In addition, they have long been debated to confer cardioprotective benefits. The French Paradox is an observation of a low prevalence of ischemic heart disease, with high intakes of saturated fat, a phenomenon accredited to the consumption of red wine. Although many epidemiological investigations have supported this view, others have attributed it to beer or spirits, with many suggesting that the drink type is not important. Although excessive consumption of alcoholic beverages is commonly regarded to be detrimental to cardiovascular health, there is a debate as to whether light-to-moderate intake is cardioprotective. Although there is extensive epidemiological support for this drinking pattern, a consensus has not been reached. On the basis of published work, we describe the composition of wine and the effects of constituent polyphenols on chronic cardiovascular diseases.
68 The bifidobacterium longum 35624® culture transits in high numbers through the human gut
Authors: S Healy, M Casey, B Kiely, EM Quigley, F Shanahan, EF Murphy
Journal: Gut (2017)

Background  Most probiotic products rely on in vitro laboratory tests to assess transit and lack data on survival through the human gastrointestinal tract (GIT). However, in vitro tests are not representative of the multiple physiological states of the gut.  Aim  To confirm transit of the Bifidobacterium longum35 624 strain, found in Alflorex®, in different formats in humans.  Method  35 624 strain was administered in a capsule, straw, sachet or milk format to volunteers for 7 days at doses ranging from 1x107–1 × 1010 CFU/day (n=1–6) followed by a wash-out period. The transit of viable 35 624 strain through the human GIT was assessed from stool collected at various timepoints by bifidobacteria selective agar plates and/or typing representative colonies using strain-specific PCR.  Results  Independent of form, the 35 624 strain transited in humans to high numbers, ranging from 1 × 104 – 1 × 108 CFU/g of stool in a dose-dependent manner at Day 7. Furthermore, despite antibiotic use in a 10-year-old cystic fibrosis sufferer (250 mg Zithromax 3 times/week), the 35 624 strain transited well (≥1 × 106 CFU/g). Co-administration of the antibiotic and probiotic resulted in a 1 log decrease in levels recovered from stool compared to administration of the probiotic 12 hour post antibiotic.  Conclusion  Independent of delivery format, the 35 624® strain was detected in stool at day 7 in a viable form at levels greater than 1×104 CFU/g of stool. Transit of viable 35 624® strain in a patient with long term antibiotic use was confirmed demonstrating that the Zithromax did not affect the 35 624® viability under the conditions of the experiment.
Inflammatory bactericidal lectin RegIIIβ: Friend or foe for the host?
Authors: Tsuyoshi Miki, Nobuhiko Okada, Wolf-Dietrich Hardt
Journal: Gut Microbes (2017)

In the inflamed gut, the bactericidal lectin RegIIIβ is massively produced by intestinal mucosa. RegIIIβ binds peptidoglycan and lipid A respectively, and thus can kill certain Gram-positive and Gram-negative bacteria, including the gut commensal microbiota and enteropathogenic bacteria. Considering the expression pattern and bactericidal activity, RegIIIβ is believed to be a host defense factor for protecting against the infection with enteropathogenic bacteria. However, it was poorly understood how RegIIIβ recognizes the target bacteria and kill them, and how RegIIIβ plays role(s) in infectious diarrhea. Therefore, our recent study has focused on RegIIIβ-target recognition, killing of Gram-negative bacteria, and host protective functions of RegIIIβ for infectious diarrhea inflicted by Salmonella Typhimurium. Here, we discuss novel insights into the protective role of RegIIIβ in infectious diarrhea, and propose avenues towards novel therapeutic interventions for Salmonella diarrhea.
Immune reconstitution and survival of 100 SCID patients post–hematopoietic cell transplant: a PIDTC natural history study
Authors: Jennifer Heimall, Brent R. Logan, Morton J. Cowan, Luigi D. Notarangelo, Linda M. Griffith, Jennifer M. Puck, Donald B. Kohn, Michael A. Pulsipher, Suhag Parikh, Caridad Martinez, Neena Kapoor, Richard O’Reilly, Michael Boyer, Sung-Yun Pai, Frederick Goldman, Lauri Burroughs, Sharat Chandra, Morris Kletzel, Monica Thakar, James Connelly, Geoff Cuvelier, Blachy J. Davila Saldana, Evan Shereck, Alan Knutsen, Kathleen E. Sullivan, Kenneth DeSantes, Alfred Gillio, Elie Haddad, Aleksandra Petrovic, Troy Quigg, Angela R. Smith, Elizabeth Stenger, Ziyan Yin, William T. Shearer, Thomas Fleisher, Rebecca H. Buckley, Christopher C. Dvorak
Journal: Blood (2017)
Surveillance of tuberculosis in the WHO European region in 1995 : results of the feasibility study
Authors: A Perrocheau, V Schwoebel, J Veen
Journal: Eurosurveillance (1998)

Efforts to assess the changing epidemiology of tuberculosis (TB) in Europe have been limited by differences in definitions and in the quality of tuberculosis surveillance systems between countries. In order to standardise the surveillance of TB among Euro
GW28-e0958 Hypoxia-Inducible Factor-2α Activation in Vascular Smooth Muscle Cells Accelerates Atherogenesis in ApoE-/- Mice
Authors: Dan Qi, Yanting Song, Xia Wang, Shiyu Jiao, Huihua Li, Jie Du, Aijuan Qu
Journal: Journal of the American College of Cardiology (2017)
Regional differences in overall survival (OS) in patients with advanced melanoma (MEL) who received nivolumab (NIVO) combined with ipilimumab (IPI) or NIVO alone in a phase 3 trial (CheckMate 067)
Authors: J.-J. Grob, D. Schadendorf, J. Wagstaff, I. Márquez-Rodas, C. Lebbé, P.A. Ascierto, F.S. Hodi, K. Grossmann, J.C. Hassel, D. Walker, R. Bhore, J. Larkin, J.D. Wolchok
Journal: Annals of Oncology (2017)
Infecções por Salmonella enterica serotipo Oranienburg associadas ao consumo de queijo Tirolês de fabrico local
Authors: F Allerberger, P Kreidl, M P Dierich, E Klingsbichel, D Jenewein, C Mader, D Khaschabi, M Schönbauer, C Berghold
Journal: Eurosurveillance (2000)

No Tirol (Austria), entre 10 de Agosto e 29 de Setembro de 1999, foram detectados dezasseis casos de infeccao enterica por Salmonella enterica serotipo Oranienburg confirmados por cultura. Dez apresentavam diarreia hemorragica e seis eram portadores assintomaticos. As entrevistas efectuadas a 11 doentes estabeleceram uma relacao entre o surto, e uma quinta alpina e o consumo de queijo de leite de vaca de fabrico local. Em amostras fecais colhidas no galinheiro da quinta, foi identificada uma S. Oranienburg. Nesta quinta, o galinheiro estava localizado proximo da area onde o queijo era produzido tendo as galinhas acesso a essa area.
Hunt promises affordable homes and flexible hours to retain NHS staff
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Healthcare staff in England will be offered first refusal to buy affordable housing built on surplus NHS land that is sold off, the health secretary has announced.

In his speech to the Conservative Party conference in Manchester on 3 October Jeremy Hunt also announced plans to offer NHS staff new flexible working hours arrangements to boost recruitment and retention. Hunt said that the approach, which would use a new app, would be piloted in 12 trusts from next year.

Alongside this, Hunt set out an ambitious …
Baseline characteristics and first-line (1L) treatment of patients with HER2+ metastatic breast cancer (MBC) from the SystHERs registry
Authors: P.A. Kaufman, S.A. Hurvitz, J. O'Shaughnessy, G. Mason, D.A. Yardley, A. Brufsky, H.S. Rugo, M. Cobleigh, S.M. Swain, D. Tripathy, L. Chu, V. Antao, B. Yoo, M. Jahanzeb
Journal: Annals of Oncology (2017)
CheckMate 214: Efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups
Authors: B. Escudier, N.M. Tannir, D.F. McDermott, O.A. Frontera, B. Melichar, E.R. Plimack, P. Barthelemy, S. George, V. Neiman, C. Porta, T.K. Choueiri, T. Powles, F. Donskov, P. Salman, C.K. Kollmannsberger, B. Rini, S. Mekan, M.B. McHenry, H.J. Hammers, R.J. Motzer
Journal: Annals of Oncology (2017)
Does melanoma or other skin cancers belong to the BRCA2 phenotype?
Authors: R. Vitorino, F. Vaz, A.L. Carvalho, S. Bento, A. Luís, A. Opinião, A. Clara, J. Dupont, S. Santos, P. Machado, S. Fragoso, P. Rodrigues, J. Parreira, C. Moura
Journal: Annals of Oncology (2017)
A phase III randomized study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk melanoma (U.S. Intergroup E1609): Preliminary safety and efficacy of the ipilimumab arms.
Authors: Ahmad A. Tarhini, Sandra J. Lee, F. Stephen Hodi, Uma N. M. Rao, Gary I Cohen, Omid Hamid, Laura Fulper Hutchins, Jeffrey Alan Sosman, Harriet M. Kluger, Vernon K. Sondak, Henry B. Koon, Donald P. Lawrence, Kari Lynn Kendra, David R. Minor, Carrie B. Lee, Mark R Albertini, Lawrence E. Flaherty, Teresa M. Petrella, John M. Kirkwood
Journal: Journal of Clinical Oncology (2017)

9500 Background: In the U.S., 3 regimens have regulatory approval as adjuvant therapy for high-risk melanoma, including high-dose interferon-alfa (HDI) and ipilimumab 10 mg/kg (ipi10). Ipilimumab 3 mg/kg (ipi3) has regulatory approval for metastatic inoperable melanoma. The toxicity of ipi is dose- dependent, and following the recent approval of adjuvant ipi10, it has become urgent to evaluate the relative safety and efficacy of adjuvant ipi at the 2 dose levels that have been tested in E1609. Methods: E1609 randomized patients (pts) with resected high-risk melanoma (stratified by stages IIIB, IIIC, M1a, M1b) to ipi10 or ipi3 versus HDI. Co-primary endpoints were RFS and OS. The current analysis investigates the relative safety and preliminary, non-comparative RFS of the ipi arms as of 3/2/17. Results: E1609 was activated on 5/25/11 and completed adult pt accrual on 8/15/14. Accrual to ipi10 was suspended due to toxicity between 9/23-11/16/2013. Final adult pt accrual was 1670 including 511 ipi10, 636 HDI and 523 ipi3 pts. Treatment related adverse events (AEs) were reported among 503 ipi10 and 516 ipi3 pts. Worst degree (Gr 3+) AEs were experienced by 57% ipi10 and 36.4% ipi3 pts and were mostly immune related (Table 1). AEs led to discontinuation of treatment in 271 (53.8 %) of 503 ipi10 and in 180 (35.2 %) of 512 ipi3 pts during the initial 4 dose induction phase. Gr5 AEs considered at least possibly related were 8 with ipi10 and 2 with ipi3. At a median follow-up of 3.1 years, an unplanned RFS analysis of ipi3 and ipi10 on concurrently randomized pts showed no difference between the 2 arms. Three-year RFS rate was 54% (95% CI: 49, 60) with ipi10 and 56% (50, 61) with ipi3. Conclusions: Adjuvant therapy of pts with high-risk melanoma is associated with significantly more toxicity at ipi10 compared to ipi3. An unplanned RFS analysis of concurrently randomized pts on the 2 ipi arms showed no difference in RFS. Clinical trial information: NCT01274338. [Table: see text]
Paxillin Binding to the Cytoplasmic Domain of CD103 Promotes Cell Adhesion and Effector Functions for CD8+ Resident Memory T Cells in Tumors
Authors: Ludiane Gauthier, Stéphanie Corgnac, Marie Boutet, Gwendoline Gros, Pierre Validire, Georges Bismuth, Fathia Mami-Chouaib
Journal: Cancer Research (2017)

CD8+/CD103+ tissue-resident memory T cells (TRM cells) accumulate in several human solid tumors, where they have been associated with a favorable prognosis. However, the role of CD103, the α subunit of the integrin αEβ7 (also known as CD103), in the retention and functions of these TRM is undefined. In this report, we investigated the role of CD103 cytoplasmic domain and the focal adhesion-associated protein paxillin (Pxn) in downstream signaling and functional activities triggered through αE/CD103 chain. Binding to immobilized recombinant (r)E-cadherin-Fc of CD103 integrin expressed on tumor-specific CTL clones promotes phosphorylation of Pxn and Pyk2 and binding of Pxn to the αE/CD103 subunit tail. Inhibition of Pxn phosphorylation by the Src inhibitor saracatinib or its knockdown via shRNA dramatically altered adhesion and spreading of freshly isolated CD8+/CD103+ lung tumor-infiltrating lymphocytes and CD103+ tumor-specific CTL clones. Inhibition of Pxn phosphorylation with saracatinib in these CTL clones also severely compromised their functional activities toward autologous tumor cells. Using Jurkat T cells as a model to study CD103 integrin activation, we demonstrated a key role of serine residue S1163 of the αE chain intracellular domain in polarization of CD103 and recruitment of lysosomes and Pxn at the contact zone of T lymphocytes with rE-cadherin-Fc-coated beads. Overall, our results show how Pxn binding to the CD103 cytoplasmic tail triggers αEβ7 integrin outside-in signaling that promotes CD8+ T-cell migratory behavior and effector functions. These results also explain the more favorable prognosis associated with retention of TRM cells in the tumor microenvironment. Cancer Res; 77(24); 7072-82. ©2017 AACR.
Evaluation of the Second Generation of a Bioresorbable Everolimus Drug-Eluting Vascular Scaffold for Treatment of De Novo Coronary Artery Stenosis
Authors: Patrick W. Serruys, Yoshinobu Onuma, John A. Ormiston, Bernard de Bruyne, Evelyn Regar, Dariusz Dudek, Leif Thuesen, Pieter C. Smits, Bernard Chevalier, Dougal McClean, Jacques Koolen, Stephan Windecker, Robert Whitbourn, Ian Meredith, Cécile Dorange, Susan Veldhof, Karine Miquel-Hebert, Richard Rapoza, Hector M. García-García
Journal: Circulation (2010)

Background— The first generation of the bioresorbable everolimus drug-eluting vascular scaffold showed signs of shrinkage at 6 months, which largely contributed to late luminal loss. Nevertheless, late luminal loss was less than that observed with bare metal stents. To maintain the mechanical integrity of the device up to 6 months, the scaffold design and manufacturing process of its polymer were modified. Methods and Results— Quantitative coronary angiography, intravascular ultrasound with analysis of radiofrequency backscattering, and as an optional assessment, optical coherence tomography (OCT) were performed at baseline and at a 6-month follow-up. Forty-five patients successfully received a single bioresorbable everolimus drug-eluting vascular scaffold. One patient had postprocedural release of myocardial enzyme without Q-wave occurrence; 1 patient with OCT-diagnosed disruption of the scaffold caused by excessive postdilatation was treated 1 month later with a metallic drug-eluting stent. At follow-up, 3 patients declined recatheterization, 42 patients had quantitative coronary angiography, 37 had quantitative intravascular ultrasound, and 25 had OCT. Quantitative coronary angiography disclosed 1 edge restenosis (1 of 42; in-segment binary restenosis, 2.4%). At variance with the ultrasonic changes seen with the first generation of bioresorbable everolimus drug-eluting vascular scaffold at 6 months, the backscattering of the polymeric struts did not decrease over time, the scaffold area was reduced by only 2.0% with intravascular ultrasound, and no change was noted with OCT. On an intention-to-treat basis, the late lumen loss amounted to 0.19±0.18 mm with a limited relative decrease in minimal luminal area of 5.4% on intravascular ultrasound. OCT showed at follow-up that 96.8% of the struts were covered and that malapposition of at least 1 strut, initially observed in 12 scaffolds, was detected at follow-up in only 3 scaffolds. Mean neointimal growth measured by OCT between and on top of the polymeric struts equaled 1.25 mm 2 , or 16.6% of the scaffold area. Conclusion— Modified manufacturing process of the polymer and geometric changes in the polymeric platform have substantially improved the medium-term performance of this new generation of drug-eluting scaffold to become comparable to those of current drug eluting stents. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT00856856.
Use of NGS for stratification of patients with advanced NSCLC within the NHS using FFPE-extracted DNA from diagnostic biopsies
Authors: S. Subramaniam, M.A. Cerone, D. McBride, P. Rehal, A. Rettino, J. Bell, H. Roberts, M. Macdonald, R. Butler, S. MacMahon, L. Thompson, C. Middleton, R. Sharpe, I. Walker, P. Johnson
Journal: Annals of Oncology (2017)
Chronic treatment with folic acid improves nitric oxide bioavailability and decreases superoxide production in human vessels, through tetrahydrobiopterin-mediated improvement of eNOS coupling
Authors: C A Antoniades, C Shirodaria, J Lee, M Carptree, C Ratnatunga, R Pillai, S Neubauer, K Channon
Journal: Journal of the American College of Cardiology (2007)
A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide and cisplatin (API), followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). Update at 10 years
Authors: P. Pautier, C. Brard, A. Floquet, L. Gladieff, M. Rios, S. Piperno-Neumann, D. Berton-Rigaud, J.-Y. Blay, M. Fabbro, J.-P. Lotz, A. Vinceneux, F. Bertucci, T. De La Motte Rouge, C. Guillemet, C. Genestie, F. Duffaud
Journal: Annals of Oncology (2017)

Background: There is no proven benefit of adjuvant treatment in uterine sarcoma (US). SARCGYN was a phase-III study which compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B). The study met its primary end point (3-year progression-free survival (PFS)) and showed a statistical increase of the 3-year PFS in the chemo+RT arm (A) vs radiation arm (B) (55% and 41% respectively, [P = 0.048]) after a median follow-up of 4.3 years (Ann Oncol 2013). Secondary end-point was overall survival (OS) that required a longer follow-up. Methods: Patients with FIGO stage ≤III US, and physiological age ≤65 years were randomized after complete surgery and normal thoracic, abdominal and pelvic CT scans between CT and no CT, with a stratification between carcinosarcomas (CS) versus others. Study was stopped earlier because of lack of recruitment. All patients received pelvic RT (45 grays); vaginal brachytherapy was optional. Chemotherapy consisted in four cycles of doxorubicin 50 mg/m2, d1; ifosfamide 3 g/m2/day d1-2; cisplatin 75 mg/m2, d3; + G-CSF q 3 weeks. Results: Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, and 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, and 19 carcinosarcomas. API was toxic with two toxic deaths and one acute leukemia. After a median FU of 9.9 years [0.3-15.1], 42/81 patients relapsed, 16 in arm A, and 26 in arm B, and 38 died, 16 in arm A, and 22 in arm B. The 5-year OS is 74% in arm A and 60% in arm B, and the difference is not significant (p = 0.16). Conclusions: In this trial interrupted at an early stage and with a longer follow-up, there is no statistical impact of API adjuvant CT on OS. The two toxic deaths and the integration of carcinosarcomas may have impacted on the global prognosis. A selection of a specific uterine population and a less toxic chemotherapy for future studies are mandatory. Clinical trial identification: NCT00162721 Legal entity responsible for the study: Institut de Cancérologie Gustave Roussy Funding: Association pour la Recherche contre le Cancer; Chugaï Pharma Disclosure: P. Pautier: Advisory board: Roche and Pharmamar. S. Piperno-Neumann: Travel grants PharmaMar, Novartis. F. Bertucci: Traveling grants, PharmaMar, Novartis. F. Duffaud: Consultancy work: Lilly, Pharmamar, Bayer, Novartis Travel grants: Pfizer, Pharmamar. All other authors have declared no conflicts of interest.