tbuckley/cabot-search huggingface dataset:
ACTR-11. OVERALL SURVIVAL IN GLIOBLASTOMA PATIENTS TREATED WITH OPTUNE® CORRELATES WITH COMPLIANCE: CONSISTENCY ACROSS STUDIES
Authors: Wyatt Potter, Bimal Shah, Melissa Shackelford, Joe Davis, Charles Boatwright, Jeanine Certo
Journal: Neuro-Oncology (2017)

Optune® is an FDA-approved portable medical device that delivers continuous treatment with Tumor-Treating Fields (TTFields) to the supratentorial region of the brain and is indicated for the treatment of newly diagnosed glioblastoma multiforme (GBM) in combination with temozolomide and for recurrent GBM as a monotherapy. TTFields are alternating electric fields that disrupt charged proteins involved in cell division thereby serving as an anti-mitotic therapy. The delivery of TTFields to the brain is achieved with externally applied transducer arrays that are attached to the shaved scalp and powered by the TTFields generator. There is no half-life associated with TTFields, meaning that once the device is powered off, therapy immediately halts. The device maintains an internal log reflecting the time on and off and thereby provides an objective measure of daily duration of therapy – termed compliance. Subset analyses from two phase 3 pivotal trials; EF-14 and EF-11, as well as a commercial patient registry dataset (PRiDe) have consistently demonstrated that patient compliance on Optune of ≥75%, which equates to a monthly average of ≥18 hours per day, correlates with a statistically significant increase in overall survival compared to patients with ˂75% compliance. The duration of therapy, i.e. the number of months of active treatment, also positively correlates with survival and tumor response. Due to the survival benefit conferred by compliance and duration of therapy, strategies that increase the safe use and integration of Optune into the activities of daily living of GBM patients, will maximize the chance for patients to respond to therapy and should be part of the medical oversight of Optune-treated patients. Optune is an innovative regional therapy and standard treatment option for GBM whose efficacy relies on informed healthcare practitioners and effective patient self-management to remain compliant while managing practical issues and skin irritation associated with this therapy.
P3.05-008 Potential of CYFRA 21-1 and HE4 to Detect Recurrence in Patients with Early-Stage Lung Adenocarcinoma
Authors: T. Muley, Y. He, V. Rolny, B. Wehnl, A. Escherich, A. Warth, C. Stolp, M. Schneider, H. Dienemann, M. Meister, F. Herth, F. Dayyani
Journal: Journal of Thoracic Oncology (2017)
Diaphragmatic Breathing Reduces Belching and Proton Pump Inhibitor Refractory Gastroesophageal Reflux Symptoms
Authors: Andrew Ming-Liang Ong, Laura Teng-Teng Chua, Christopher Jen-Lock Khor, Ravishankar Asokkumar, Vikneswaran s/o Namasivayam, Yu-Tien Wang
Journal: Clinical Gastroenterology and Hepatology (2017)
Campaña de vacunación contra la enfermedad meningocócica en una zona rural de los Países Bajos – Enero de 1998
Authors: J. E. van Steenbergen, A. G. Kraayeveld, L Spanjaard
Journal: Eurosurveillance (1999)

Neisseria meningitidis del grupo C causa regularmente epidemias en colegios, universidades y unidades militares, y en la ultima decada se han declarado brotes comunitarios (1). Desde la aparicion de una eficaz vacuna polisacarida, con frecuencia se plantea si debe administrarse o no y cuando. La delimitacion del grupo diana a vacunar es siempre una tarea dificil, puesto que es un proceso arbitrario definido por varias consideraciones.
MA 17.04 Initial Surgery in Patients with Clinical N2 Non-Small Cell Lung Cancer: A Multi-Institution Retrospective Study
Authors: T. Maniwa, Y. Shintani, J. Okami, M. Ohta, Y. Takeuchi, K. Takami, H. Yokouchi, E. Kurokawa, R. Kanzaki, Y. Sakamaki, H. Shiono, T. Iwasaki, K. Nishioka, K. Kodama, M. Okumura
Journal: Journal of Thoracic Oncology (2017)
P2.01-075 Genomic Changes and Clinical Characteristics Associated with Wood-Smoke Exposure in Patients with Non-Small Cell Lung Cancer
Authors: N. Hernandez-Pedro, G. Soca-Chafre, C. Alaez, K. Carrillo-Sanchez, P. Barrios-Bernal, O. Arrieta
Journal: Journal of Thoracic Oncology (2017)
P2.02-035 PD-L1 IHC Test on Cytological Cell Block Specimen; Potential Utility and Practical Issues
Authors: M. Sugiyama, T. Hashimoto, K. Yoshida, Y. Shibuki, S. Watanabe, N. Yamamoto, Y. Ohe, N. Motoi
Journal: Journal of Thoracic Oncology (2017)
P3.01-066 CNS Metastases of Pulmonary Adenocarcinoma Harboring EGFR-Activating Mutations: a Multidisciplinary Approach, Including EGFR-TKis
Authors: G. Harada, R. Bonadio, G. Marta, T. Takahashi, T. Takagaki, G. De Castro
Journal: Journal of Thoracic Oncology (2017)
ANGI-17. GLIOBLASTOMA STEM CELLS EXPLOIT THE ALPHAVBETA8 INTEGRIN-TGFBETA SIGNALING AXIS TO DRIVE TUMOR INITIATION AND PROGRESSION
Authors: Joseph McCarty, Erik Sulman, Ganesh Rao, Qianghu Wang, Fred Lang, Paola Guerrero
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is a primary brain cancer that contains populations of stem-like cancer cells (GSCs) that home to specialized perivascular niches comprised of vascular endothelial cells, pericytes and extracellular matrix (ECM)-rich basement membranes. Interactions with their niche influence GSC self-renewal, differentiation and drug resistance, although the pathways underlying these events remain largely unknown. Here, we report that the adhesion receptor alphavbeta8 integrin and its ECM-bound latent transforming growth factor beta1 (TGFbeta1) protein ligand play central roles in promoting niche co-option and GBM initiation. alphavbeta8 integrin is highly expressed in GSCs and is essential for self-renewal and lineage commitment in vitro. Inhibition of alphavbeta8 integrin adhesion and signaling using function-blocking antibodies inhibit sphere formation in vitro. Fractionation of beta8high cells from freshly resected human GBM samples also reveals a requirement for this integrin in sphere formation in vitro and tumor growth and invasion in vivo. In contrast, fractionated beta8low GBM cells fail to form spheroids in vitro and do not generate tumors after intracranial implantation. Whole transcriptome sequencing of primary GBM cells reveals that alphavbeta8 integrin promotes tumor initiation in the brain, in large part, by driving TGFbeta1-induced DNA replication and mitotic checkpoint progression. We show that beta8high cells activate latent TGFbeta1 in the microenvironment, resulting in enhanced TGFbeta receptor signaling in beta8low GBM cells and tumor endothelial cells via Smad transcription factors. Collectively, these data identify the alphavbeta8 integrin-TGFbeta1 signaling axis as crucial for exploitation of the perivascular niche and identify potential therapeutic targets for inhibiting tumor growth and progression in patients with GBM.
Neutrophil-to-lymphocyte ratio in metastatic breast cancer patients: relationship with tumor characteristics and survival
Authors: M. Bartoletti, L. Gerratana, S. Zago, D. Basile, V. Fanotto, M.G. Vitale, G. Pelizzari, M. Bonotto, C. Bozza, C. Lisanti, M. Cinausero, S. Barban, M. Lera, I. Venuti, M. Mansutti, A.M. Minisini, G. Fasola, F. Curcio, F. Puglisi
Journal: Annals of Oncology (2017)
SCDT-39. NANOBIOCONJUGATES CROSSING BBB FOR DELIVERY OF CHECKPOINT INHIBITORS AND ACTIVATION OF LOCAL BRAIN TUMOR IMMUNE SYSTEMS FOR GLIOMA TREATMENT
Authors: Julia Ljubimova, Hui Ding, Anna Galstyan, Antonella Chiechi, San Tao, Eketerina Shatalova, Manuel Penichet, Alexander Ljubimov, Eggehard Holler, Keith Black
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme (GBM) still has limited treatment options. We introduce a new generation of nanobioconjugates that deliver anti-CTLA-4 and/or anti-PD-1 antibodies through blood-brain barrier (BBB) and activate local brain tumor immune response directed against GBM. Immuno-nanobioconjugates (INC) based on natural polymer, poly b(L-malic acid) (P) and crossing BBB were synthesized: P/PEG/msTfR/anti-CTLA-4 and P/PEG/msTfR-pTfR/anti-PD-1 (MsTfR and pTfR are anti-transferrin receptor antibody and peptide, respectively). Physico-chemical, pharmacological, and toxicological parameters of INCs were determined. Syngeneic GL261 glioma cells were intracranially inoculated into C57/BL mice. Treatment groups were injected 5 times I.V. with either PBS, or anti-PD1 and anti-CTLA4 as a control, or polymer conjugated to anti-PD1(P/PD1), anti-CTLA-4 (P/CTLA-4) or a combination (P/CTLA-4+P/PD-1) at 5 or 10 mg/kg, with a new premedication regimen to reduce immunotoxicity. INC P/CTLA-4 and P/PD-1 significantly improved brain tumor-bearing mice survival compared with free anti-CTLA-4 and anti-PD-1 (p<0.05 and p<0.009). The combination P/CTLA-4 + P/PD1 resulted in the highest survival compared with anti-CTLA-4 (p<0.01), anti-PD-1 (p<0.03), and PBS (p<0.003) groups. Flow cytometry analysis of T cells in brain tumors revealed reduction of the number of CD4+ T-cells in animals treated with P/PD-1 and combination P/CTLA-4+P/PD1. The fraction of Tregs (CD4+FOXP3+) was also reduced by all polymer conjugates compared to free antibodies. Activation of CD8+ T-cells (CD8+IFNγ+ and CD8+CD69+) was significantly increased by P/CTLA-4, P/PD-1, and by combination INC therapy compared to controls. Multiplex assay to measure the cytokine response to treatment demonstrated significant increase of IL-1β, IL-2, TNFα, IL-6, IL-12, and IFNγ in the brain and serum after INC combination therapy compared to controls. Brain tumor treatment with polymer-conjugated antibodies to PD-1 and CTLA-4 crossing BBB significantly increased animal survival, supported by immunological results indicating the activation of anti-tumor T-cell populations locally in the brain. Support: NIH grants U01 CA151815, R01 CA136841, CA206220
18F-sodium fluoride (18F-NaF) PET/CT scan for the assessment of brain metastases (BMs)
Authors: A. Inno, M. Salgarello, F. Severi, S. Pasetto, L. Romano, G. Carbognin, F. Marchetti, G. Gorgoni, R. Casolino, P. Cassandrini, M. Cirillo, R. Magarotto, A. Modena, M. Nicodemo, V. Picece, M. Turazza, F. Alongi, M. Valerio, G. Lunardi, S. Gori
Journal: Annals of Oncology (2017)
Epidémies d’infections à E. coli O157 au sud-ouest du Royaume-Uni : risques associés aux cours d’eaux traversant les plages
Authors: C Ihekweazu, M Barlow, S Roberts, H Christensen, B Guttridge, D A Lewis, S Painter
Journal: Eurosurveillance (2006)

En aout 2004 sept cas d’infection a Escherichia coli O157 ont ete identifies chez des enfants en vacances dans le Cornouailles, au sud-ouest de l’Angleterre, chacun ayant sejourne dans des sites differents de la region. La presence d’E. coli de serogroupe O157 et de phage type 21/28 a ete confirmee dans les isolats des sept cas. Une etude cas-temoin a ete menee parmi les vacanciers qui avaient frequente la plage. Un questionnaire standardise a ete soumis par telephone aux parents. Parmi les questions figuraient la plage frequentee par leur enfant, le fait d’avoir ete en contact en non avec le cours d’eau traversant la plage, ainsi que leurs lieux d’achat de nourriture et les sources des aliments consommes. Les cas avaient plus frequente le cours d’eau que les controles (OR [1.72- non defini]). Le temps passe dans le cours d’eau par les cas etait le double de celui des controles. L’exposition aux autres facteurs de risque consideres etait identique entre les cas et les controles. Les profils d’electrophorese en champ pulse de tous les cas etaient indiscernables les uns des autres. Une augmentation du nombre de coliformes dans le cours d’eau avant la survenue de l’epidemie a ete mise en evidence, et il s’est avere que du betail paissait en amont. Les auteurs suggerent que le vehicule de l’infection de cette epidemie de gastroenterite aigue a E. coli O157 etait ce cours d’eau contamine qui se deversait sur la plage. Les dates d’apparition des premiers symptomes etaient compatibles avec ce point source. Les fortes pluies les jours qui ont precede l’epidemie pourraient avoir entraine une contamination du cours d’eau par les dejections du betail potentiellement contamine par E. coli O157, provoquant ainsi l’epidemie. Des mesures de controle ont ete prises dont l’installation d’une barriere autour de la partie du cours d’eau dans laquelle les enfants jouaient, et la mise en place de panneaux d’avertissement autour de la plage.
Abstract 18885: CTRP1, an Adipokine Causing Endothelial Dysfunction Through Upregulation of Arginase 1, is Associated With the Severity of Coronary Artery Disease in Patients and Promotes Atherogenesis in Mice
Authors: Xiao Qun Wang, Lin Lu, Rui Yan Zhang, Zhu Hui Liu, Ying Shen, Ling Jie Wang, Xiao Xiang Yan, Raffaele De Caterina, Wei Feng Shen
Journal: Circulation (2015)

Background: C1q/TNF-related protein (CTRP) 1 was initially identified as a paralog of adiponectin based on the similarity in C1q domain of these two proteins. However, vascular functions of CTRP1 remain largely undetermined. Here, we sought to investigate whether CTRP1 influences the pathogenesis of atherosclerosis. Methods and Results: We analyzed CTRP1 levels in sera of coronary artery disease (CAD) patients (n=451) and non-CAD controls (n=686), in coronary endarterectomy specimens (n=26) and non-atherosclerotic internal mammary arteries (n=32), and in peripheral blood mononuclear cells (PBMCs) from severe CAD patients (n=58) and non-CAD controls (n=25). CTRP1 levels were higher in sera, endarterectomy specimens and PBMCs from CAD patients compared with controls, and were related to CAD severity. Immunohistochemistry of human femoral arteries exhibited VE-cadherin loci-associated increased CTRP1 expression in atherosclerotic plaques. In cultured endothelial cells, CTRP1 stimulation resulted in reduced nitric oxide (NO) bioavailability and promotion of inflammatory reactions (increased production of inflammatory cytokines and induction of adhesion molecules). Intravital microscopy exhibited impaired endothelium-dependent arteriole dilation and enhanced leukocyte-endothelium interactions after injection of recombinant CTRP1, whereas improved arteriole dilation and decreased leukocyte-endothelium interactions were observed in CTRP1 knockout mice. Furthermore, we found that arginase 1 was significantly increased by CTRP1 in a dose-dependent fashion, thereby leading to eNOS-uncoupling and reactive oxygen species generation. Inhibition of arginase activity by synthetic chemicals markedly improved CTRP1-dependent endothelial dysfunction. Finally, intraperitoneal injection of recombinant CTRP1 promoted atherogenesis in apoE-/- mice. In contrast, proatherogenic effects were significantly attenuated in CTRP1-/-/apoE-/- double knockout mice. Conclusions: Our findings have demonstrated that CTRP1 is a pro-atherogenic adipokine, likely by modulating arginase 1 expression and enzyme activity. CTPP1 may represent a crucial therapeutic target in atherosclerosis.
ACTR-88. A PHASE II STUDY OF THE EFFICACY OF HYPOFRACTIONATED RADIATION THERAPY WITH BEVACIZUMAB AND TEMOZOLOMIDE FOLLOWED BY MAINTENANCE TEMOZOLOMIDE AND BEVACIZUMAB FOR RECURRENT HIGH-GRADE GLIOMAS
Authors: Karan Dixit, Priya Kumthekar, Timothy Kruser, Sean Sachdev, John A Kalapurakal, Vinai Gondi, Sean Grimm, Martin Nicholas, Rimas V Lukas, Steven J Chmura, Minesh P Mehta, Jeffrey Raizer
Journal: Neuro-Oncology (2017)

Patients with recurrent high grade glioma (rHGG) have a poor prognosis with limited treatment options, especially those refractory to bevacizumab. A phase II multi-center trial was performed to determine the overall survival (OS) of hypofractioned radiation with concurrent bevacizumab (BEV) and temozolomide (TMZ) followed by maintenance BEV and TMZ in patients with rHGG. Inclusion criteria were recurrent anaplastic glioma (AG) or glioblastoma (GBM) with patients stratified into 4 groups based on histologic grade and prior exposure to bevacizumab (Bev). Treatment consisted of hypofractionated radiation at 1.8 Gy for 25 fractions (45Gy total dose) concurrent with bevacizumab 10mg/kg every 2 weeks and temozolomide 75mg/m2 daily followed by adjuvant treatment cycles (8 week cycles) of bevacizumab 10mg/kg every 2 weeks and temozolomide 50mg/m2 daily for 6 weeks. Primary endpoint was overall survival (OS). Fifty-four patients were treated (37 men, 17 women). Median age was 49 (range 21–72). Of the 54 patients, 31 were Bev exposed GBM, 7 were Bev naïve GBM, 6 were Bev exposed AG, and 3 were Bev naïve AG. OS for Bev exposed GBM was 7.5 months, 15.0 months for Bev naïve GBM, and 5.0 months for Bev exposed AG. All Bev naïve AG patients are still living. Median OS for all patients with prior Bev exposure was 7.5 months. Grade 3 and 4 toxicities included lymphopenia (grade 3, n=4; grade 4, n=1) and thrombocytopenia (grade 3, n=1; grade 4, n =1). The combination of hypofractionated reirradiation, bevacizumab, and temozolomide was relatively safe and showed modest activity in recurrent high-grade glioma patients, including those with progressive disease while on bevacizumab.
Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen–negative chronic hepatitis B
Authors: Wen‐Juei Jeng, Yi‐Cheng Chen, Rong‐Nan Chien, I‐Shyan Sheen, Yun‐Fan Liaw
Journal: Hepatology (2017)

Hepatitis B surface antigen (HBsAg) loss is a rare event during nucleos(t)ide analogue (Nuc) therapy. Limited data suggest that stopping Nuc therapy may increase HBsAg loss rate in hepatitis B e antigen–negative patients. A large study was conducted to investigate this issue in more detail. Of the 1,075 hepatitis B e antigen–negative patients treated with Nuc for a median of 156 (61‐430) weeks, 5 showed HBsAg seroclearance during treatment at an estimated annual incidence of 0.15%. Of the patients who remained HBsAg‐seropositive, 691 (52.3 years old, 86% male, 44.6% cirrhosis) had stopped Nuc therapy by the Asian‐Pacific Association for the Study of the Liver stopping rule and then were prospectively followed up. Baseline and on‐treatment clinical and viral features, treatment duration, consolidation duration, time to undetectable hepatitis B virus DNA, time to normal alanine aminotransferase, end‐of‐treatment HBsAg, and HBsAg log reduction were compared between patients with and without HBsAg seroclearance after end of treatment. During a median off‐therapy follow‐up period of 155 (2‐614) weeks, HBsAg seroclearance was confirmed in 42 patients. The 6‐year cumulative incidence was 13% with an estimated annual incidence of 1.78%. Cox regression analysis showed that shorter time to undetectable hepatitis B virus DNA (&lt;12 weeks), greater HBsAg reduction during therapy (&gt;1 log 10 ), lower end‐of‐treatment HBsAg level (&lt;100 IU/mL), patients with sustained response, and relapsers not retreated were factors for off‐therapy HBsAg seroclearance. Conclusion: The incidence of HBsAg seroclearance after stopping Nuc was much higher than that during therapy and highest in patients without virologic and clinical relapse; patients with clinical relapse who remained untreated had a 7.34 times higher incidence of HBsAg clearance than those who received retreatment, suggesting that transient untreated clinical relapse may drive sufficient immune control to functional cure. (H epatology 2017).
Compliance to diagnostic and therapeutic pathways and innovative drug recommendations in advanced non-small cell lung cancer: preliminary results from the MOST study
Authors: G. Pasello, G. Vicario, S. Gori, F. Zustovich, A. Bonetti, F. Rosetti, A. Favaretto, F. Oniga, E. Bria, S. Toso, M. Boccalon, C. Oliani, G. Palazzolo, S. Frega, M. Basso, P. Pertile, A. Bortolami, R. Verrienti, R. Scanni, P. Conte
Journal: Annals of Oncology (2017)
Efficacy of extended aromatase inhibitors for hormone-receptor–positive breast cancer: a literature based meta-analysis of randomized trials
Authors: G. Roviello, O. Pagani, F. Meani, C. Strina, D. Zanoni, M. Milani, N. Sohbani, A. Ianza, M. Bortul, F. Zanconati, P. Rossellini, D. Generali
Journal: Annals of Oncology (2017)
ACTR-87. THE RESIDUAL TUMOR VOLUME MAY AFFECT THE EFFICACY OF BCNU WAFER FOR MALIGNANT GLIOMAS
Authors: Mario Suzuki, Satoshi Adachi, Akihide Kondo
Journal: Neuro-Oncology (2017)

Recently, a favorable outcome of meta-analysis on the efficacy of BCNU wafer with Stupp regimen for malignant glioma was published, however, it is not clear about the appropriate case selection of the usage of BCNU wafer. Therefore, we reviewed our cases and compare the efficacy of BCNU wafer based on the residual tumor volume and molecular characters with histopathological diagnosis. Fifty-four cases were enrolled this study. We used BCNU wafer in 26 cases and did not used in 28 cases. The average age was 57.5 and the gender ratio was 1:1.3 (male: female). The end point of progression free survival (PFS) was decided based on the deterioration of patients’ performance status and the radiological progression of tumors. We experienced one major complication, severe brain edema. However the other minor events were controllable and did not affect the patients’ outcome in the usage of this agent. The PFS was not reached because of the shortage of observation periods and the less of numbers. However, in the group of 5cc or less residual tumor volume, the PFS was significantly longer than in the group of more residual tumor volume, statistically. (p=0.0034) Our results suggest that BCNU wafer should be use when gross total resection was achieved and the residual tumor volume should be less than 5cc for the safe and good treatment outcome.
Abstract 20763: Automatic Detection of Ventilation Waveforms From the Bioimpedance Signal During Chest Compression Pauses
Authors: Elisabete Aramendi, Yuanzheng Lu, Mary P Chang, Andoni Elola, Unai Irusta, Ahamed H Idris
Journal: Circulation (2017)

Introduction:  Because of limited evidence, the role of ventilation during cardiopulmonary resuscitation (CPR) is not well understood. Effective ventilation provided during 30:2 CPR has been linked to better prognosis in small studies, but definitive evidence is lacking.   Hypothesis:  Prior to placement of an advanced airway, only the electrocardiogram and bioimpedance signals are recorded during CPR. This study proposes to create an automated algorithm that uses bioimpedance recordings to detect ventilation (lung inflation) during 30:2 CPR.   Methods:  We analyzed data from the Dallas Fort-Worth site of the Resuscitation Outcomes Consortium Continuous vs. Interrupted Chest Compression Clinical Trial. Bioimpedance recordings from Physio-Control Lifepak 12 and 15 defibrillators were reviewed and analyzed from initial CPR until the time of advanced airway placement. A pause was defined as an interruption in chest compressions of 3 to 15 seconds.A ventilation waveform was defined as a single waveform with an amplitude >0.5 Ω and upstroke (inhalation) and down stroke (exhalation) intervals >0.5 s. For waveforms that overlap with chest compressions, the criteria were applied only to the exhalation or inhalation interval. Two independent clinicians reviewed and annotated the recordings using the defined criteria (inter-rater reliability score of 0.89). Those annotations were used as a gold standard for the automated algorithm. An automated electronic algorithm was developed in Matlab. We analyzed sensitivity (SE), specificity (SP), percentage of correctly detected pauses with and without ventilation waveforms, respectively, and the 95% confidence intervals.   Results:  The electronic files of 560 patients with 7404 pauses were processed. Of these, 2375 pauses had detectable ventilation waveforms and 5029 pauses did not. The ventilation detection algorithm showed SE= 90.8% (89.5-91.9) and SP= 92.6% (91.9-93.3).   Conclusions:  We created a novel, automated software program that can accurately discriminate chest compression pauses with and without ventilations based on the bioimpedance signal. This method can be used to evaluate ventilation during 30:2 CPR and allow ventilation metrics to be included in analyses for future resuscitation studies.