tbuckley/cabot-search huggingface dataset:
P04.23 Functional MRI as a potential biomarker for concentration deficits in brain tumor patients
Authors: I. T. Schouwenaars, M. J. de Dreu, G. J. M. Rutten, N. F. Ramsey, J. M. Jansma
Journal: Neuro-Oncology (2017)

Introduction: Brain tumor patients frequently complain about problems with concentration and focus. These problems can greatly affect the socio-professional quality of life of patients. Unfortunately, the underlying neurobiological cause of these problems is still largely unclear. In order to better understand these complaints, we are currently looking for functional MRI-biomarkers for concentration. We define concentration as a state of the brain that facilitates cognitive performance. In a previous fMRI study with healthy controls we found that concentration was specifically associated with inhibition of the brain activity in the extended area around the posterior cingulate (ePCC). Here, we present results of an ongoing patient study, where we compared brain activity in ePCC between HC and brain tumor patients before and after surgery, during tasks that required a high level of concentration on visual stimuli. Materials and Methods: Participants performed a task in which they needed to detect the letter ‘X’ among other consonants presented visually in a fast sequence. While this task is relatively simple, it does require a high level of continuous concentration. At the time of submission of this abstract, functional MRI scans were acquired in 20 healthy controls (HC), as well as in 11 brain tumor patients pre-surgery (4 low grade glioma, 7 meningioma). Five patients were also scanned 3 months after surgery (2 low grade glioma, 3 meningioma). For all scans, we calculated the percentage signal change in the ePCC. The deactivation in ePCC was compared between HC and tumor patients pre- as well as post-surgery (independent sample t-tests). In addition, we compared activity in ePCC in the subgroup of patients with a pre- and post-surgery fMRI scan (paired sample t-test). Results: All participants executed the task well, with very few incorrect responses. Before surgery, patients showed stronger deactivation in ePCC than HC, and this difference was near significant (t = 2.01, p = 0.053). After surgery, patients also showed stronger deactivation than HC (t = 5.51, p <0.001). In the small subgroup of patients with both pre- and post-surgery scans, we found a trend towards stronger deactivation in ePCC after surgery (t = 2.39, p = 0.076). Conclusions: Our study indicates that patients show greater deactivation of the ePCC during tasks that require a high level of concentration, while maintaining normal performance. Preliminary results indicate that this effect may become even larger after surgery. The greater deactivation may be caused by an increased vulnerability for interfering processes in the brain. Alternatively, it may be a result of a reduced capability to optimally tune the brain to the task.
P10.25 Low-grade gliomas analysis of 45 cases
Authors: R. Rodríguez, V. Verdier
Journal: Neuro-Oncology (2017)

Introduction: Grade 2 Gliomas are relatively uncommon, constituting 2 to 10% of all primary brain tumors in adults. In general they appear in early ages, with a high incidence between 35 to 40 years. Even though it is still a controversial issue, the complete surgical excision has shown the better impact on survival. Despite of Gliomas have long survival, they tend to reappear progressively and change to high histologic levels. Risk factors associated with poor survival could be, age over 40 years, astrocytoma, tumor size and neurologic deficit before surgery. PATIENTS AND METHODS: This is a retrospective, descriptive observational study. The main objective is to analyze into the medical records, the clinical presentation, the histology and treatment received in patients with low -grade gliomas (grade II according to the WHO -World Health Organization), as well as to analyze the progression-free survival and overall survival. Data was collected from the files of the patients assisted by the Neuro-Oncology Unit at Hospital de Clínicas Dr. Manuel Quintela-Montevideo. Uruguay, between 1991 May and 2011 March. Results: Forty five medical records were reviewed. The median age of presentation was 38 years (from 15 to 82 years), 58% were men, and 42% women. Convulsions (33%) were common and expected, 82% had imagenologic diagnosis through tomography, 60% were located in the frontal region. Regarding histology, 77% were oligodendroliomas, 16% astrocytomas and 7% oligoastrocytomas. Treatment perfomed in first place was surgery exclusively. Surgery with complete excision was found in 22% of patients, incomplete excision in 27%, partial in 27%, biopsia 13%. 4% received radiotherapy exclusively, 2% chemotherapy exclusively and 2% obervation. Chemotherapy used by itself or associate with other treatments were, Carmustina 70%, Procarbacina 20% and Carboplatin -Etoposide 10%. In the first relapse, 80% went under surgery again, evolving to grade III in 33% of the patients. The median progression-free survival was of 112 months while the median overall survival was of 140 months. Conclusions: Oligodendrogliomas were the most frequent low grade Gliomas in our revision and regarding survival, they not differ in comparison with internationals reports. Age ≥ 40 and tumoral size ≥ 6 cm were independent risk factors, in the multiple variable analyses. Eventually, a molecular profile study, could demonstrate which tumor characteristics as well as the weight of treatment intervention may have an impact in survival.
P04.06 Gold nanoparticles development for Raman guided Glioblastoma visualization during surgical resection
Authors: F. Burgio, D. Piffaretti, L. Mariani, U. Pieles, M. Reinert
Journal: Neuro-Oncology (2017)

Increasing the extent of resection has been associated with prolonged overall survival in Glioblastoma (GBM). Conventional imaging technologies applied in neurosurgery supply essential information about tumor size and localization, nevertheless they still fail in identifying true tumor extents because of low sensitivity, limited spatial resolution and depth of penetration. For example, 5-aminolevulinic acid (ALA) induced fluorescence resection has shown to improve the quality of the resection, however it suffers from several limitations, notably false negative fluorescent areas. To address this issue, Raman microscopy has emerged as a promising tool in cancer treatment, as visualization can be specifically targeted on tumor specific biomolecular cell surface epitopes. For increased sensitivity of Raman scattering, gold nanoparticles (GNPs) are used. When properly engineered, they selectively target cancer cells and, due to their distinct optical and physical properties, provide contrast agents for accurate mapping of tumor spread. In this study, surface enhanced Raman scattering (SERS) GNPs are developed as reliable means for image-guided GBM resection. Since about 50% of GBM express the epidermal growth factor receptor (EGFR), this protein is chosen as specific tumoral target. GNPs functionalization involves several steps including the attachment of a Raman active molecule, a polyethylene glycol (PEG) shell to increase gold colloidal stability, and the conjugation with anti-EGFR antibodies. Successful GNP surface functionalization has been confirmed, and currently the functionality of the conjugate, i.e. its binding affinity and kinetics, is being monitored by Quartz Crystal Microbalance (QCM-D). GNPs selectivity for EGFR is also analyzed in vitro in cultured human GBM cell lines expressing different EGFR levels. As such, GNPs selection will be defined by testing their ability to cross an artificial Blood Brain Barrier (BBB) before performing in vivo analysis in a xenograft mouse model. Surface enhanced Raman microscopy, based on application of anti-EGFR-GNPs, opens new surgical strategies to improve intraoperative diagnosis and visualization of GBM margins during surgical resection. This work is supported by Prof. Dr. med. Michael Reinert, head of Brain Tumor Research Group, Cantonal Hospital Corporation of Lugano.
Phase I study of ridaforolimus with cetuximab for patients with advanced non-small cell lung cancer (NSCLC), colorectal cancer, and head and neck cancer.
Authors: Angela Marie Taber, Humera Khurshid, Kimberly Perez, Ariel E. Birnbaum, Adam J. Olszewski, Denise Luppe, Maureen Jean, Kayla Rosati, Howard Safran
Journal: Journal of Clinical Oncology (2013)

8075 Background: mTOR inhibition may overcome PI3K/AKT pathway mediated resistance to anti-EGFR therapy. We performed a phase I study to determine the dose-limiting toxicity (DLT) of ridaforolimus, an investigational oral mTOR inhibitor, in combination with the anti-EGFR antibody cetuximab. Methods: Patients with advanced NSCLC, colorectal cancer, and head and neck cancer that progressed after at least 1 prior regimen for metastatic disease were eligible. ECOG performance status 0-1. Patients with previously treated brain metastases that were stable for &gt;3 months were eligible. Wild-type K-RAS was required in colon cancer. All patients received cetuximab 400 mg/m 2 week 1 followed by 250 mg/m 2 weekly. Three dose levels of ridaforolimus were planned: 20mg, 30mg, and 40mg daily, 5 days each week, on a 28-day cycle. Results: 12 patients were entered with NSCLC (n=7), colon cancer (n=4), and head and neck cancer (n=1). The median age was 58 (42-69). The median number of prior regimens for metastatic disease, by disease type, was NSCLC (n=3), colorectal (n=4), head &amp; neck (n=4). Three patients completed the first dose level without DLT. Two of 3 patients at dose level 2 had dose-limiting mucositis. The first dose level was then expanded with six additional patients with NSCLC without any further dose-limiting toxicities. The recommended phase II dose of ridaforolimus is 20 mg daily, 5 days a week, in combination with cetuximab. Response and prolonged stable disease was demonstrated in NSCLC. Conclusions: The DLT of the combination of ridaforolimus and cetuximab is mucositis. The activity observed in heavily pretreated patients with NSCLC suggests that the combination of an mTOR inhibitor with an EGFR antibody merits further investigation in NSCLC. Clinical trial information: NCT01212627.
P12.03 Prognostic value of TERT promoter Mutation in aggressive meningiomas
Authors: A. Biczok, T. Kraus
Journal: Neuro-Oncology (2017)

Introduction: Transcriptional activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene occur at high frequency in various types of solid tumors. In atypical and anaplastic meningiomas, however incidence and significance of TERT mutations are still largely unkown. The aim of the present study was to investigate the frequency of TERT promoter mutations in a cohort of atypical and anaplastic meningiomas and to define prognostic significance for progression free survival and overall survival. Methods: Patients undergoing surgical resection of WHO grade II and WHO grade III meningiomas from 01/2001 to 12/2014 were included into the analysis. TERT analysis for C228T and C250T mutations in the TERT promoter region was performed using PCR method. Patients were stratified into 2 groups (TERT mutation vs. TERT wild type). Univariate and multivariate analysis was conducted using molecular and histological factors as well as surgical features. Results: During the follow up time of 38.5 months, 88 patients with atypical (n=73) and anaplastic meningiomas (n=15) were included in the study. TERT promoter region C228T or C250T mutation was found to be mutated in 4 WHO grade II (5.5%) and 2 WHO grade III (13.3%) meningiomas. Presence of TERT mutations were equally distributed between genders (present in 5.7% female and 7.5% of male patients), age did not differ between the subgroups. Meningiomas harboring TERT mutation did not show a strong predilection for any location, with an equally distribution between convexity (n=3) and skull base location (n=3). Presence of a TERT mutation was associated with shorter progression free survival than TERT wild type (median PFS 12.5 months vs 26 months). In the multivariate analysis, TERT promoter mutation had a strong independent prognostic value on overall survival (median OS 26 months vs 40 months) in aggressive meningiomas (p=0.009 HR=4.872). Conclusion: Presence of TERT promoter mutation variant C228T and C250T was associated with shorter PFS and OS in aggressive meningiomas. TERT mutation status should be considered a clinically relevant prognostic factor in meningiomas WHO grade II and III identifying patients at higher risk for recurrence and progression.
Wireless Capsule Gastrointestinal Endoscopy: Direction-of-Arrival Estimation Based Localization Survey
Authors: Nilanjan Dey, Amira S. Ashour, Fuqian Shi, R. Simon Sherratt
Journal: IEEE Reviews in Biomedical Engineering (2017)

One of the significant challenges in capsule endoscopy (CE) is to precisely determine the pathologies location. The localization process is primarily estimated using the received signal strength (RSS) from sensors in the capsule system through its movement in the gastrointestinal (GI) tract. Consequently, the wireless CE (WCE) system requires improvement to handle the lack of the capsule instantaneous localization information and to solve the relatively low transmission data rate challenges. Furthermore, the association among the capsule's transmitter position, capsule location, signal reduction, and the capsule direction should be assessed. These measurements deliver significant information for the instantaneous capsule localization systems based on time-of-arrival approach, phase difference of arrival, RSS, electromagnetic, direction of arrival (DOA), and video tracking approaches are developed to locate the WCE precisely. This review introduces the acquisition concept of the GI medical images using the endoscopy with a comprehensive description of the endoscopy system components. Capsule localization and tracking are considered to be the most important features of the WCE system, thus this paper emphasizes the most common localization systems generally, highlighting the DOA-based localization systems and discusses the required significant research challenges to be addressed.
Waist measurement, not BMI, is stronger predictor of death risk, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

People with a normal body mass index (BMI) but a large waist circumference have worse long term survival than people who are overweight or obese but who do not carry their weight around the middle, a study has found. The finding, published in Annals of Internal Medicine ,1 is consistent with previous research but is from a much larger sample of adults in the general population.

The study included 42 702 participants …
The Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5): Background and rationale
Authors: Gavin A Davis, Laura Purcell, Kathryn J Schneider, Keith Owen Yeates, Gerard A Gioia, Vicki Anderson, Richard G Ellenbogen, Ruben J Echemendia, Michael Makdissi, Allen Sills, Grant L Iverson, Jiří Dvořák, Paul McCrory, Willem Meeuwisse, Jon Patricios, Christopher C Giza, Jeffrey S Kutcher
Journal: British Journal of Sports Medicine (2017)

This article presents the Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5). The Sport Concussion Assessment Tool was introduced in 2004, following the 2nd International Conference on Concussion in Sport in Prague, Czech Republic. Following the 4th International Consensus Conference, held in Zurich, Switzerland, in 2012, the SCAT 3rd edition (Child SCAT3) was developed for children aged between 5 and12 years. Research to date was reviewed and synthesised for the 5th International Consensus Conference on Concussion in Sport in Berlin, Germany, leading to the current revision of the test, the Child SCAT5. This article describes the development of the Child SCAT5.
OS05.1 The D-2-hydroxyglutarate product of mutant IDH1 induces synchronized neuronal firing via NMDA receptor activation
Authors: H. Chen, J. Judkins, F. Ghamsari, P. Lein, C. Horbinski
Journal: Neuro-Oncology (2017)

Seizures diminish the quality of life in patients with diffusely infiltrative gliomas. Over 50% of patients will experience at least one seizure during the course of their disease, and over 30% will develop tumor-associated epilepsy (TAE), defined as multiple seizures. Because the D-2-hydroxyglutarate (D2HG) product of mutant isocitrate dehydrogenase 1 (IDH1mut) is released by tumor cells into the microenvironment, and D2HG is structurally similar to the excitatory neurotransmitter glutamate, we sought to determine whether IDH1mut increases the risk of seizures in glioma patients, and whether D2HG increases the electrical activity of neurons. Three cohorts of WHO grade II-IV gliomas, from separate institutions (total N=712), were retrospectively assessed for the presence of preoperative seizures. Such seizures were noted in 18–34% of IDH1 wild-type (IDH1wt) patients and in 59–74% of IDH1mut patients (P<0.001). Multivariable analysis, including WHO grade, 1p/19q codeletion, and temporal lobe tumor location, showed that IDH1mut was an independent correlate with seizures (OR=2.5, 95% CI=1.6–3.9, P<0.001). Furthermore, exogenous D2HG increased the synchronized firing rate of cultured rat cortical neurons by 400–600%, but was completely blocked by AP5, a selective NMDA antagonist. Our data therefore suggests that the D2HG product of IDH1mut increases neuronal activity by mimicking the activity of glutamate on the NMDA receptor, and that this is the reason why IDH1mut gliomas are more likely to cause seizures in patients. Our data has rapid translational implications for the personalized management of TAE, as targeted IDH1mut inhibitors may improve antiepileptic therapy in patients with IDH1mut gliomas.
Screening for Preeclampsia During Pregnancy
Authors: Jill Jin
Journal: JAMA (2017)

US Preventive Services Task Force; Kirsten Bibbins-Domingo, PhD, MD, MAS; David C. Grossman, MD, MPH; Susan J. Curry, PhD; Michael J. Barry, MD; Karina W. Davidson, PhD, MASc; Chyke A. Doubeni, MD, MPH; John W. Epling Jr, MD, MSEd; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Ann E. Kurth, PhD, RN, MSN, MPH; C. Seth Landefeld, MD; Carol M. Mangione, MD, MSPH; William R. Phillips, MD, MPH; Maureen G. Phipps, MD, MPH; Michael Silverstein, MD, MPH; Melissa A. Simon, MD, MPH; Chien-Wen Tseng, MD, MPH, MSEE
Disease-free and overall survival at 3.5 years for neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin and cyclophosphamide, for women with HER2 negative early breast cancer: ARTemis Trial
Authors: H.M. Earl, L. Hiller, J.A. Dunn, C. Blenkinsop, L. Grybowicz, A.-L. Vallier, I. Gounaris, J.E. Abraham, L. Hughes-Davies, K. McAdam, S. Chan, R. Ahmad, T. Hickish, D. Rea, C. Caldas, J.M.S. Bartlett, D.A. Cameron, E. Provenzano, J. Thomas, R.L. Hayward
Journal: Annals of Oncology (2017)

The ARTemis trial previously reported that addition of neoadjuvant bevacizumab (Bev) to docetaxel (D) followed by fluorouracil, epirubicin and cyclophosphamide (D-FEC) in HER2 negative breast cancer improved the pathological complete response (pCR) rate. We present disease-free survival (DFS) and overall survival (OS) with central pathology review.Patients were randomized to 3 cycles of D followed by 3 cycles of FEC (D-FEC), ±4 cycles of Bev (Bev + D-FEC). DFS and OS were analyzed by treatment and by central pathology reviewed pCR and Residual Cancer Burden (RCB) class.A total of 800 patients were randomized [median follow-up 3.5 years (IQR 3.2-4.4)]. DFS and OS were similar across treatment arms [DFS hazard ratio (HR)=1.18 (95% CI 0.89-1.57), P = 0.25; OS HR = 1.26 (95% CI 0.90-1.76), P = 0.19). Both local pathology report review and central histopathology review confirmed a significant improvement in DFS and OS for patients who achieved a pCR [DFS HR = 0.38 (95% CI 0.23-0.63), P < 0.001; OS HR = 0.43 (95% CI 0.24-0.75), P = 0.003]. However, significant heterogeneity was observed (P = 0.02); larger improvements in DFS were obtained with a pCR achieved with D-FEC than a pCR achieved with Bev + D-FEC. As RCB class increased, significantly worse DFS and OS was observed (P for trend <0.0001), which effect was most marked in the ER negative group.The addition of short course neoadjuvant Bev to standard chemotherapy did not demonstrate a DFS or OS benefit. Achieving a pCR with D-FEC is associated with improved DFS and OS but not when pCR is achieved with Bev + D-FEC. At the present time therefore, Bev is not recommended in early breast cancer.NCT01093235.
The Value of Using Registries to Evaluate Randomized Clinical Trial Study Populations
Authors: Adam J. Schoenfeld, Rita F. Redberg
Journal: JAMA Internal Medicine (2017)

Thomas M. Maddox, MD, MSc; Fengming Tang, MS; John R. Downs, MD; Frederick A. Masoudi, MD, MSPH; Salim S. Virani, MD, PhD; Stacie L. Daugherty, MD; John S. Rumsfeld, MD, PhD
P08.36 TGF-β pathway-mediated escape from VEGF blockade is linked with angiogenesis and immune-suppression in murine glioma models
Authors: D. Mangani, M. Weller, E. Seyed Sadr, E. Willscher, K. Seystahl, G. Reifenberger, G. Tabatabai, H. Binder, H. Schneider
Journal: Neuro-Oncology (2017)

The vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β are key target molecules in glioblastoma that are interdependently regulated. Both pathways drive key malignant features in glioma cells such as angiogenesis, invasiveness and immunosuppression. Here we explore whether TGF-β acts as an escape pathway from VEGF inhibition using gene expression profiling and in vitro and in vivo studies in a panel of syngeneic mouse glioma models. In vivo, single agent activity was observed for the VEGF antibody B20-4.1.1 in three (SMA-540, SMA-560 and GL-261), and for the TGF-β receptor I antagonist LY2157299 in two (SMA-540 and SMA-560) of four mouse glioma models. Transcriptomic profiling of the four mouse glioma models revealed that SMA-497 and GL-261, while unresponsive to LY2157299, were the most immunogenic tumors as defined by Gene Ontology; specifically, up-regulation of chemokine/chemoreceptors genes involved in immune cell recruitment and interferon-related genes were found. Co-targeting of VEGF and TGF-β was ineffective in one refractory model (SMA-497), in which no major changes in tumor immune-infiltrating cells were detected upon mono- or co-treatment settings. Significant prolongation of survival in the GL-261 model was associated with early stage increased infiltration of CD8+ cells, lower numbers of CD11b+ macrophages/microglia and sustained suppression of angiogenesis compared to anti-VEGF treatment alone. Phosphorylated SMAD2 was increased in both tumor cells and CD45+ leukocytes during anti-angiogenic treatment pointing to the possibility of a TGF-β-induced immunosuppressive micro-milieu that is efficiently counteracted by concomitant administration of LY2157299. In conclusion, our study highlights the biological heterogeneity of glioblastoma even among simple mouse models and illustrates that co-targeting of the VEGF and TGF-β pathways might lead to improved tumor control in subsets of glioblastoma linked with angiogenesis impairment and general reduction of the immune-suppressive phenotype. This study was supported by a grant from Oncosuisse (KFS-02694-08-2010)