tbuckley/cabot-search huggingface dataset:
Cabozantinib for the treatment of patients with metastatic variant histology renal cell carcinoma (vhRCC): a retrospective study
Authors: M.T. Campbell, M.A. Bilen, C. Duran, E. Altinmakas, Z. Lim, A. Shah, E. Jonasch, N. Tannir
Journal: Annals of Oncology (2017)

Background: Cabozantinib (C) prolongs overall survival (OS) and progression-free survival (PFS) in patients with metastatic clear-cell renal cell carcinoma (ccRCC) that progressed on first-line VEGFR-TKI. No standard of care systemic therapy exists for the management of patients with metastatic vhRCC. Methods: This is a retrospective, IRB approved study of patients with vhRCC who received cabozantinib at MD Anderson Cancer Center from January 2014-January 2017. Information collected from the medical records included the baseline characteristics, toxicity, dose reductions, and OS. A blinded radiologist assessed the radiographic response using RECIST v1.1. Descriptive statistics, the Kaplan Meier method and the log rank test were applied using Microsoft Excel and GraphPad Prism version 6 software. Results:Table912PN = 30GenderMale = 26 (86.7%)Age, median (range)58.4 years (25-81)Prior Nephrectomy27 (90%)HistologyPapillary (P) 17 Chromophobe (Chr) 6 Other: unclassified 3, translocation 2, sarcomatoid (sarc) 1, mucinous tubular/spindle cell 1Prognostic Risk Group MSKCC IMDCGood/Intermediate/Poor 2/20/8 2/23/5Number of Prior Therapies 0 1 >1 Median (range) Previous VEGFR Tyrosine Kinase Inhibitor3 7 20 2 (0-5) 26 Open table in a new tab Median PFS was 8.6 months (mos) (95%CI: 6.1-14.7), and median OS was 22.7 mos (95%CI:10.8-NR), median follow up 10.6 months (95%CI: 7.1-14.1). There were no significant differences detected between patients with papillary versus non-papillary histologies with respect to PFS or OS. At last follow up, 13 patients remain on treatment with median time on therapy for all patients of 15.0 months. Of the 28 patients with measurable disease, there were 4 confirmed PRs (2 P, 1 Chr, 1 unclassifed) for a 14% ORR. For the entire cohort, 20 of 30 (66.7%) with stable disease, and 6 of 30 with progressive disease (20%), for a disease control rate of 24 of 30 (80%). Of 21 patients who started C at 60 mg/d, 12 (57%) required dose reduction due to toxicity. Multiple patients required treatment breaks but none discontinued therapy due to toxicity. Conclusions: In this retrospective study, C produced a clinically meaningful benefit in patients with metastatic vhRCC, the majority of whom had PD on prior VEGFR-TKIs. Prospective trials of C in vhRCC are warranted and planned. Legal entity responsible for the study: Matthew T Campbell Funding: None Disclosure: M.T. Campbell: Serve on advisory boards for Eisai and AstraZeneca. M.A. Bilen: Advisory board for Exelixis. N. Tannir: Served as a consultant and has served on advisory board for Exelixis. All other authors have declared no conflicts of interest.
Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion
Authors: Yongqiang Liu, Larra W. Yuelling, Yuan Wang, Fang Du, Renata E. Gordon, Jenny A. O'Brien, Jessica M.Y. Ng, Shannon Robins, Eric H. Lee, Hailong Liu, Tom Curran, Zeng-Jie Yang
Journal: Cancer Research (2017)

Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. Although astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here, we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor-associated astrocytes (TAA) secrete the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drives expression of Nestin in MB cells through a smoothened-dependent, but Gli1-independent mechanism. Ablation of TAA dramatically suppresses Nestin expression and blocks tumor growth. These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression. Cancer Res; 77(23); 6692-703. ©2017 AACR.
School absence data for influenza surveillance: a pilot study in the United Kingdom
Authors: W P Schmidt, R Pebody, P Mangtani
Journal: Eurosurveillance (2010)

School-age children are at a high risk of acute respiratory virus infections including the 2009 pandemic influenza A(H1N1). School absence records have been suggested as a tool for influenza surveillance. We analysed absence records from six primary schools (children aged from around five to 11 years) in London during the years 2005 to 2007 in order to provide baseline epidemiological characteristics of illness-related school absence, and to correlate school absence with seasonal influenza. The daily average prevalence of absence due to illness was 2.9%. The incidence was 1.3% per person-day. The mean duration of absence was 1.8 days (SD 1.8). Over 60% of absence episodes lasted for one day. Absence prevalence did not differ by sex. Prevalence was highest in the youngest children and then declined slightly, but was again high again in the oldest. Absence was slightly higher on Mondays and Fridays. In general, peaks of absenteeism coincided with peaks of influenza A and B (laboratory reports) but several high peaks were not associated with influenza. There was a better correlation between absence and laboratory reports and prevalence compared to incidence. School absence data may be useful for the detection of localised school outbreaks and as an additional surveillance tool but are limited by lack of data on weekends and during holidays.
Activity of lurbinectedin as single agent and in combination in patients with advanced small cell lung cancer (SCLC)
Authors: M.E. Olmedo Garcia, M. Forster, E. Calvo, V. Moreno, M.P. Lopez Criado, J.A. Lopez-Vilarino de Ramos, C. Kahatt, P. Lardelli, X.E. Luepke-Estefan, A. Soto-Matos
Journal: Annals of Oncology (2017)
GW28-e0138 The Predictive Value for Long-term Prognosis of Score Systems in Patients with Acute Myocardial Infarction undergoing Percutaneous Coronary Intervention
Authors: Fengqiang Dang, Lijun Wang, Xianjing Wei, Zezhou Xie, Limei Qi, Yumei Chen, Lianna Xie
Journal: Journal of the American College of Cardiology (2017)
Targeting glioma stem cells through combined BMI1 and EZH2 inhibition
Authors: Xun Jin, Leo J Y Kim, Qiulian Wu, Lisa C Wallace, Briana C Prager, Tanwarat Sanvoranart, Ryan C Gimple, Xiuxing Wang, Stephen C Mack, Tyler E Miller, Ping Huang, Claudia L Valentim, Qi-gang Zhou, Jill S Barnholtz-Sloan, Shideng Bao, Andrew E Sloan, Jeremy N Rich
Journal: Nature Medicine (2017)
Phase 2a study of a novel stapled peptide ALRN-6924 disrupting MDMX- and MDM2-mediated inhibition of wild-type TP53 in patients with peripheral t-cell lymphoma
Authors: M. Payton, D. Pinchasik, A. Mehta, S. Goel, J.M. Zain, L. Sokol, E. Jacobsen, M.R. Patel, S.M. Horwitz, F. Meric-Bernstam, A. Shustov, D. Weinstock, M. Aivado, D.A. Annis
Journal: Annals of Oncology (2017)
Immunotherapy phase I trials in patients over 70 years with advanced solid tumours: The Gustave Roussy experience
Authors: H. Herin, E. Castanon, V. Dyevre, S. Aspeslagh, A. Marabelle, S. Postel-Vinay, A. Varga, A. Gazzah, V. Ribrag, R. Bahleda, J-M. Michot, O. Mir, C. Massard, A. Hollebecque, J-C. Soria, C. Baldini
Journal: Annals of Oncology (2017)
Potential miRNAs involved in molecular pathways mediating the anticancer effects of short term starvation in breast cancer cells treated with doxorubicin
Authors: D. Fanale, L. Incorvaia, R. Maragliano, N. Barraco, A. Listì, A. Galvano, S. Rizzo, V. Calò, L.R. Corsini, V. Bazan, A. Russo
Journal: Annals of Oncology (2017)
Phase 1 dose-escalation study of single-agent ZW25, a HER2-targeted bispecific antibody, in patients (pts) with HER2-expressing cancers
Authors: M. Beeram, E. Hamilton, M. Blum Murphy, D. Hausman, J.R. Infante, R. Korn, A. Patnaik, S.A. Piha-Paul, D. Rasco, G. Rowse, J. Thimmarayappa, A. Tolcher, F. Meric-Bernstam
Journal: Annals of Oncology (2017)
“Golden hello” of £20 000 to be offered to 200 GPs a year, says health secretary
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Trainee GPs will be offered £20 000 (€22 000; $26 000) “golden hellos” if they opt to work in parts of England that are struggling to recruit, the health secretary, Jeremy Hunt, has said.

Speaking at the Royal College of General Practitioners’ annual conference in Liverpool on 12 October, Hunt said that the “salary supplements” would be available to 200 GPs from next year in areas of the country where training places had been unfilled for three or more years.

Similar schemes running in areas hard to recruit to had so far used “golden hellos” 126 times, with a success …
Immune Suppression By High-Density Neutrophils Predicts Short Progression-Free Survival in Multiple Myeloma
Authors: Alessandra Romano, Jose Manteiga, Vittorio Simeon, Nunziatina L Parrinello, Cesarina Giallongo, Piera La Cava, Concetta Conticello, Daniele Tibullo, Francesca Fontana, Fabio Ciceri, Floriana Cremasco, Monica Fabbri, Pellegrino Musto, Simone Cenci, Francesco Di Raimondo
Journal: Blood (2016)
A feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for locally advanced gastric cancer
Authors: A. Takashima, D. Takahari, N. Ishizuka, H. Katai, T.E. Nakajima, M. Ohashi, S. Mikami, S. Takahashi, T. Sano, N. Boku, K. Yamaguchi
Journal: Annals of Oncology (2017)
Pharmacokinetics of a nucleoside analogue CP-4055 in two phase I trials using a daily for 5 days schedule and three intermittent weekly or biweekly schedules
Authors: Eric Raymond, Svein Dueland, Mike J. Lind, Ahmad Awada, Hilary Thomas, Stéphane Culine, Alejandro Yovine, William Sutherland, Tone Grande, Wenche Rasch
Journal: Cancer Research (2005)

3975  Introduction: CP-4055 (5’-elaidic acid ester of Ara-C, Clavis Pharma AS, Oslo, Norway) is a novel cytotoxic agent based on the Lipid Vector Technology with a wide spectrum of preclinical antitumour activity in solid tumours due to improved uptake and resistance to deamination. We report pharmacokinetic (PK) results from two phase I trials, exploring a daily x 5 schedule (sch) and weekly and biweekly sch. Methodology: Using standard dose-finding designs, patients (pts) with solid tumours received CP-4055 as a 30 min infusion, daily x 5 q3 wks, over a 30-200 mg/m2/infusion dose range in Trial 1, and as a 2 hour infusion in Trial 2 according to 3 sch: days 1, 8 q3 wks (Sch A); days 1, 15 q4 wks (Sch B); days 1, 8, 15 q4 wks (Sch C), over the range 100 to 480 mg/m2/infusion. PK was assessed on day 1 and day 4 (Trial 2 only) of cycle 1. Samples were taken at hour (hr) 0:00, 0:15, 0:30, 0:35, 0:45, 1:00, 1:30, 2:00, 2:30, 4:30, 7:30, 10:30, 24:30 in Trial 1; and 0:00, 1:00, 2:00, 2:05, 2:15, 2:30, 3:00, 4:00, 6:00, 9:00, 24:00 in Trial 2. Plasma assay used a validated liquid chromatography with tandem mass spectrometric detection method. Non-compartmental analysis was employed. Results: As of Nov 2004, 37 pts (Trial 1: 23, Trial 2: 14) were evaluable for day 1 PK and 21 for day 4. Pt characteristics: male/ female: 13/24, mean age: 55.0 (27-79), mean weight (kg): 70.8 (47-111). Pharmacokinetics over all dose levels: CP-4055 AUC increased linearly with planned dose/m2 (Trial 1: R2=0.76, Trial 2: R2=0.94) as did CP-4055, Ara-C and Ara-U Cmax (R2: from 0.69 to 0.98). Interpatient variation of PK parameters was low, being mostly  80%). CP-4055 plasma elimination was biphasic in both trials for doses >30 mg/m2/infusion. CP-4055 and Ara-C were undetectable at 24 hr in the majority of pts, with t½α
Méthodes pour une surveillance virologique sentinelle de la grippe en Europe, une étude sur 18 pays
Authors: T J Meerhoff, A Meijer, W J Paget
Journal: Eurosurveillance (2004)

Le Programme europeen de surveillance de la grippe (European Influenza Surveillance Scheme, EISS) est base sur un modele de surveillance clinique et virologique integre. Afin d'evaluer la comparabilite des donnees virologiques, un questionnaire a ete envoye aux participants en juin 2002 portant sur le recueil de prelevements, le diagnostic biologique de la grippe et les analyses pour d'autres infections respiratoires. 
Les resultats montrent des differences, mais egalement une certaine uniformite, quant aux methodes de recueil des donnees virologiques. Certaines similitudes ont ete rapportees au niveau des methodes de recueil des prelevements ; le type de prelevement et les conditions de transport etaient comparables. Les methodes de diagnostic etaient diverses. Des differences ont ete notes quant aux methodes de (sous) typage, la PCR etant plus souvent utilisee dans les pays d'Europe occidentale. Les resultats serviront a interpreter les donnees virologiques recueillies par les medecins sentinelle et a la creation d'un Reseau communautaire de laboratoires de references pour la grippe chez l'homme. Les principaux objectifs du reseau sont l'harmonisation des methodes virologiques et l'application du programme qualite controle pour les laboratoires nationaux de reference.
GW28-e0644 Quantitative Measurement of Circumferential Aortic Strain by 2D Speckle Tracking Echocardiography improves Diagnostics of Coronary Artery Stenosis in suspected patients
Authors: Jun Ma, Zhaohui Bu, Xuedong Shen, Zhiqing Qiao, Wei Wang, Yu Kang, Ying Zheng, Yongping Du, Jun Pu, Ben He
Journal: Journal of the American College of Cardiology (2017)
Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1
Authors: Giulia Schiroli, Samuele Ferrari, Anthony Conway, Aurelien Jacob, Valentina Capo, Luisa Albano, Tiziana Plati, Maria C. Castiello, Francesca Sanvito, Andrew R. Gennery, Chiara Bovolenta, Rahul Palchaudhuri, David T. Scadden, Michael C. Holmes, Anna Villa, Giovanni Sitia, Angelo Lombardo, Pietro Genovese, Luigi Naldini
Journal: Science Translational Medicine (2017)

Preclinical studies establish the conditions for safe and effective correction of SCID-X1 by targeted gene editing of hematopoietic stem cells.
Bidirectional chemotherapy in gastric cancer (GC) with peritoneal carcinomatosis (PC) combining intravenous chemotherapy with pressurized intraperitoneal aerosol chemotherapy (PIPAC): Results of 103 procedures in 52 patients
Authors: V. Khomyakov, A. Ryabov, L. Bolotina, A. Utkina, A. Ivanov, O. Kuznetsova
Journal: Annals of Oncology (2017)
ESEN: comparación de los programas de vacunación - Segunda parte: tos ferina
Authors: D Lévy-Bruhl, R G Pebody, K Osborne, I Veldhuijzen, M Valenciano
Journal: Eurosurveillance (1998)

Este articulo es el segundo de una serie de tres articulos sobre comparacion de programas de inmunizacion, calendarios vacunales, cobertura de vacunas e impacto de la vacunacion contra la difteria, tos ferina, sarampion, parotiditis y rubeola en ocho paises (Dinamarca, Inglaterra y Gales, Alemania, Italia, Finlandia, Francia, Paises Bajos y Suecia). El analisis ha sido llevado a cabo en el marco del proyecto financiado por la Union Europea Red Europea de Seroepidemiologia (European Sero-Epidemiology Network, ESEN) (1). Este articulo presenta los resultados correspondientes a la tos ferina.
BEECH: A randomised Phase 2 study assessing the efficacy of AKT inhibitor AZD5363 combined with paclitaxel in patients with ER+ve advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population
Authors: N. Turner, E. Alarcón, A. Armstrong, M. Philco, Y.A. López Chuken, M-P. Sablin, K. Tamura, A. Gomez Villanueva, J.A. Pérez-Fidalgo, A. Foxley, J. Lindemann, R. Maudsley, E. Outhwaite, M. Pass, P. Rugman, G. Schiavon, M. Oliveira
Journal: Annals of Oncology (2017)
Predicted benefits of adjuvant sorafenib after nephrectomy for renal cell carcinoma (RCC) in SORCE: an international, placebo-controlled, randomised phase 3 trial
Authors: N.J. Lawrence, A. Martin, I.D. Davis, S. Troon, S. Sengupta, E.J. Hovey, X. Coskinas, R. Kaplan, A.W.S. Ritchie, A. Meade, T. Eisen, P. Blinman, M.R. Stockler
Journal: Annals of Oncology (2017)
Adaptive phase II randomized non-comparative trial of nivolumab after induction treatment in triple negative breast cancer: TONIC-trial
Authors: M. Kok, H.M. Horlings, K. van de Vijver, T. Wiersma, N. Russell, L. Voorwerk, K. Sikorska, E. van Werkhoven, I.A. Mandjes, I. Kemper, J. Foekema, S. Wilgenhof, M. Chalabi, J. Stouthard, G.S. Sonke, D. Cullen, R. Salgado, T.N.M. Schumacher, C.U. Blank, S.C. Linn
Journal: Annals of Oncology (2017)
Cost-effectiveness of HER2 testing and trastuzumab therapy for metastatic breast cancer (MBC) patients in Sweden
Authors: M. Lidgren, C. Rehnberg, N. Wilking, B. Jönsson
Journal: Journal of Clinical Oncology (2007)

1088 Background: Trastuzumab is a monoclonal antibody that together with chemotherapy significantly improves time to progression and overall survival for MBC patients with tumours overexpressing HER2. The aim of this study was to analyse the cost- effectiveness of HER2 testing and trastuzumab in combination with chemotherapy compared with chemotherapy alone from a societal perspective in a Swedish setting. Methods: We used a Markov state transition model to simulate HER2 testing and subsequent treatment in a hypothetical cohort of 65 year old metastatic breast cancer patients based on the study by Marty et al (Marty et al, J Clin Oncol. Jul 1 2005;23(19):4265–4274). Outcomes included life-time costs, quality adjusted life years (QALY), and cost per QALY gained. Five different testing and treatment strategies were evaluated. Results: We estimated the cost per QALY gained to be about 485,000 SEK (approximately 70,000 USD) and the cost per life year (LY) gained to be about 332,000 SEK (approximately 47,000 USD) for the strategy of IHC testing for all patients, with FISH confirmation of 2+ and 3+, and trastuzumab and chemotherapy treatment for FISH positive patients. For the strategy of FISH testing for all patients, with trastuzumab and chemotherapy for FISH positive patients, we estimated the cost per QALY gained to about 561,000 SEK (approximately 80,000 USD) and the cost per LY gained to be 384,000 SEK (approximately 55,000 USD). The remaining testing and treatment strategies were dominated. Results were sensitive to changes in the quality adjustment of life years with metastatic disease, the risk of breast cancer related death, and test characteristics. Conclusions: Our analysis indicate that the present Swedish guidelines of IHC testing for all patients with metastatic breast cancer, with FISH confirmation of 2+ and 3+, followed by trastuzumab and chemotherapy treatment for FISH positive patients is a cost-effective treatment option. However, further research on budget impact of trastuzumab treatment and patient accessibility to trastuzumab treatment is needed. No significant financial relationships to disclose.
Dutch geriatrician faces charges over euthanasia case
Authors: Tony Sheldon
Journal: BMJ (2017)

A specialist in elderly care medicine could face prosecution under the Netherlands’ euthanasia laws after ending the life a 74 year old nursing home patient with advanced dementia.

The woman was considered no longer competent to consent but had previously signed a living will requesting euthanasia. Yet Dutch public prosecutors have launched a criminal investigation, claiming a “serious suspicion” that a criminal offence had been committed.

This is the Netherlands’ first such investigation under the reporting arrangements established in the 2002 euthanasia law.

The move came after a report by the Regional Euthanasia Review Committees, charged with overseeing euthanasia practice and to whom doctors have a legal obligation …
Adjuvant sunitinib (SU) in patients (pts) with high risk renal cell carcinoma (RCC): Safety and therapy management in S-TRAC trial
Authors: M. Staehler, R.J. Motzer, D.J. George, H.S. Pandha, F. Donskov, B. Escudier, J. Kliment, A.J. Pantuck, A. Patel, L. Deannuntis, H. Bhattacharyya, X. Lin, M. Lechuga, L. Serfass, J-J. Patard, A. Ravaud
Journal: Annals of Oncology (2017)
La politique de vaccination contre l’hépatite A pour les voyages en Egypte dans huit pays d’Europe, 2004
Authors: M Ward, K Borgen, A Mazick, M Muehlen
Journal: Eurosurveillance (2006)

En 2004, une epidemie d’hepatite A est survenue chez des touristes europeens de retour d’Egypte. Les taux d’attaque de l’infection etaient tres differents selon le pays d’origine des touristes. Afin de determiner la raison de cette divergence, une etude a ete initiee avec les objectifs suivants : (a) rassembler des informations sur les politiques nationales de prevention de l’hepatite A pour les personnes voyageant en Egypte et (b) des informations sur les pratiques de notification de l’hepatite A dans ces pays. Un questionnaire a ete elabore et envoye dans 13 pays d’Europe. Les huit pays qui ont repondu avaient tous publie des recommandations pour la prevention de l’hepatite A associee aux voyages. Entre 2001 et 2003, 40% (entre 4 et 51) des cas d’hepatite A declares chaque annee etaient associes aux voyages a l’etranger, en depit du fait que tous les pays recommandent une vaccination active contre l’hepatite A pour les voyageurs se rendant en Egypte en vacances. Il n’y avait pas de definition de cas standard pour la declaration de cas confirmes d’hepatite A dans les pays rapportant ces cas. Compte tenu du nombre croissant de touristes vers des destinations lointaines, il est vraisemblable que les infections liees aux voyages connaissent une augmentation. Face a cette situation, il faudra innover afin d’amener les voyageurs a consulter et suivre les conseils medicaux dispenses avant de partir. De plus, nous recommandons d’utiliser la definition de cas de la Commission Europeenne pour la declaration des cas confirmes d’hepatite A.
Tumor sidedness and enriched gene groups for efficacy of 1st-line cetuximab (cet) treatment in metastatic colorectal cancer (mCRC)
Authors: W. Ichikawa, K. Mogushi, H-J. Lenz, W. Zhang, A. Tsuji, T. Takahashi, T. Denda, K. Shimada, M. Kochi, M. Nakamura, M. Kotaka, Y. Segawa, B. Lafleur, J. Luecke, D. Thompson, M. Moran, S.H. Astrow, J. Hsiang, M. Fujii, Y. Sunakawa
Journal: Annals of Oncology (2017)
[Correspondence] Breast-cancer stromal cells with TP53 mutations
Authors: E.W. Thompson, A. Patocs, L. Zhang, M. Allinen, R. Beroukhim, L. Cai, S.C. Lebret
Journal: New England Journal of Medicine (2008)

To the Editor  Patocs et al.  (Dec. 20, 2007, issue)1 report a frequency of TP53 mutations in fibroblasts associated with sporadic breast carcinoma of 27.4%, and they show that mutation status is associated with regional nodal metastasis. If confirmed, this finding would represent an important discovery. We sought to confirm their findings by direct sequencing of exons 4 through 9 of TP53 in microdissected areas of stroma (<5 mm from the epithelial cancer interface) from 10 fresh-frozen sporadic breast-cancer specimens and 7 primary breast-carcinoma–associated fibroblast cultures.2,3 No mutation was detected in any of these 17 samples. The reason for this discrepancy is unclear, although we note that Patocs et al. used DNA derived from formalin-fixed, paraffin-embedded tumor tissue, which is notorious for generating polymerase-chain-reaction (PCR) artifacts.4