tbuckley/cabot-search huggingface dataset:
ATIM-28. IMMUNE PROFILES AT START OF TEMOZOLOMID-BASED STANDARD TREATMENT AND DC-BASED IMMUNOTHERAPY STRONGLY CORRELATE WITH OVERALL SURVIVAL OUTCOME IN GBM PATIENTS
Authors: Markos Antonopoulos, Stefaan Van Gool, Norbert Graf, Georgios Stamatakos
Journal: Neuro-Oncology (2017)

DC-vaccination integrated in multimodal temozolomid-based treatment for patients with GBM prolong OS in a fraction of patients. Biomarkers predicting outcome after active specific immunotherapy, however, fail. Blood samples from 134 adults, randomized for DC-vaccination during or after TMZ maintenance (TMZm), were taken before and after radiochemotherapy. Data from circulating lymphocytes were determined by FACS in 101 patients. To quantify immune profiles more systematically, nonlinear features of these data were introduced, corresponding to all meaningful ratios between immune cell subpopulations. To quantify immune profile changes during radiochemotherapy for each such quantity, the ratio of its values after/before radiochemotherapy was also calculated. Canonical correlation analysis was performed exhaustively between all possible combinations of these quantities taken 1, 2 or 3 at a time versus OS. Median OS of the total group of patients was 18 months, 2-year OS was 31.3% (+4). There was no difference in OS for patients treated with immunotherapy during versus after TMZm. Patients with postoperative residual tumor volume had a significantly worse median OS (16 versus 20 months). For the entire population, no strong correlations were detected between the immune profiles and OS. However, stratifying the patients into subgroups defined by extent of resection (residual tumor volume RTV = 0 or >0) and vaccination schedule (during or after TMZm), and repeating this analysis for each of the 4 subgroups, revealed for all subgroups strong correlations between FACS data immune profiles derived from the pre- and post-radiochemotherapy blood samples and ultimate OS of the patients. These data suggest strong influences from the immune status at start of treatment on the OS outcome of the patients. The data depict the first in silico oncology model using immune profiles to potentially predict outcome of clinical risk profile-stratified patients treated with standard treatment and immunotherapy (www.chic-vph.eu).
ATIM-17. EARLY RESULTS OF A MULTICENTER PHASE I AND OPEN-LABEL, RANDOMIZED PHASE II STUDY TESTING THE TOXICITIES AND EFFICACY OF MK-3475 (PEMBROLIZUMAB) IN COMBINATION WITH MRI-GUIDED LASER INTERSTITIAL THERMAL THERAPY (LITT) IN RECURRENT MALIGNANT GLIOMAS
Authors: Jian Campian, Ashley Ghiaseddin, Maryam Rahman, George Ansstas, Albert Kim, Eric Leuthardt, David Tran
Journal: Neuro-Oncology (2017)

LITT was recently demonstrated to induce temporary blood-brain barrier disruption, possibly allowing bilateral trafficking of tumor neoantigens and immune cells to induce glioma-specific immune activation - a phenomenon akin to in situ tumor vaccination. We hypothesize that combining LITT with immune checkpoint inhibition will create a synergistic therapy for recurrent GBM. The phase 1 study is a standard 3x3 design with a maximum of 18 patients with bevacizumab-naïve recurrent WHO grade 3–4 glioma. The primary endpoint is safety and toxicity of LITT plus pembrolizumab at 100, 150, or 200mg IV q3weeks. Phase 2 includes 40 patients with bevacizumab-naïve recurrent GBM, equally randomized to either pembrolizumab alone or LITT plus pembrolizumab. The primary endpoint is PFS. Serial immunophenotyping will be performed to evaluate potential positive synergy between LITT and pembrolizumab. Phase 1 accrual was completed with 9 patients (3 at each pembrolizumab dose level). Two had recurrent anaplastic astrocytoma and 7 recurrent GBM. As of 5/16/17, there was no dose-limiting toxicity with pembrolizumab 200mg IV q3weeks. The median number of doses given per patient was 5 (range 2 to 12). Severe adverse events possibly related to the study treatment included a grade 3 rash and diarrhea in 1 patient (11%) and grade 3 pneumonitis and hypotension in another patient (11%). No grade 3/4 intracranial edema deemed related to study treatment was observed. Best response was stable disease. One (11%), 2 (22%), and 1 (11%) GBM patients have not progressed for 20.7, 8, and 4 months, respectively. One (11%) anaplastic astrocytoma patient has not progressed for 12 months. LITT plus pemprolizumab 200mg IV q3weeks is generally well tolerated in patients with recurrent high-grade glioma. Prolonged PFS was observed in several patients. Updated study data will be presented. The study should proceed to the planned phase 2.
Incidencia y mortalidad del paludismo en Italia en 1999-2000
Authors: R Romi, D Boccolini, G Majori
Journal: Eurosurveillance (2001)

Entre 1999 y 2000, el ISS declaro un total de 2.060 casos de paludismo. Casi todos los enfermos siguieron tratamientos inadecuados o no adoptaron ningun tipo de profilaxis. El noventa y tres por ciento se infecto en paises paludicos africanos, el 4% en paises asiaticos y el 3% en America Latina. P. falciparum represento un 84% de los casos, seguido de P. vivax (8%), P. ovale (5%) y P. malariae (2%). La letalidad fue del 0,3% en 1999 y del 0,5% en 2000. En general, los casos de paludismo importado reflejan, por un lado, el numero de viajeros italianos que subestimaron el riesgo de infeccion en paises paludicos asiaticos y latinoamericanos, y, por el otro, los residentes permanentes de origen africano que visitan a sus familiares en sus paises nativos.
Intravenous Lymphoma Drug Approved
Authors: Rebecca Voelker
Journal: JAMA (2017)

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P2.13-011 Optimal Selection Criteria for LDCT Lung Cancer Screening
Authors: R. Myers, M. Ruparel, N. Taghizadeh, S. Atkar-Khattra, J. Dickson, S. Quaife, A. Bhowmik, P. Burrowes, P. Maceachern, E. Bedard, J. Yee, J.R. Mayo, J. Liu, K. Fong, C. Berg, M. Tammemägi, A. Tremblay, S. Janes, S. Lam
Journal: Journal of Thoracic Oncology (2017)
Poblaciones vulnerables : las lecciones de la ola de calor del verano de 2003 en Europa
Authors: G Brücker
Journal: Eurosurveillance (2005)

Que leccion podemos aprender de la ola de calor, excepcionalmente larga y severa, que ocurrio en Europa en 2003? Primero, que estas olas de calor pueden provocar un exceso de mortalidad considerable: mas de 50.000 muertes para Europa en agosto de 2003. Probablemente las consecuencias fueron subestimadas en muchos paises, al menos en las primeras evaluaciones. Este exceso de mortalidad afecta a grupos vulnerables, sobretodo personas mayores y enfermas. Es prioritaria la identificacion de los factores de riesgo para llevar a cabo las acciones indispensables de prevencion.
NIMG-01. DIFFUSION MRI PHENOTYPES PREDICT OVERALL SURVIVAL BENEFIT FROM ANTI-VEGF MONOTHERAPY IN GLIOBLASTOMA AT FIRST OR SECOND RELAPSE
Authors: Benjamin Ellingson, Elizabeth Gerstner, Marion Smits, Ray Huang, Rivka Colen, Lauren Abrey, Dana Aftab, Gisela Schwab, Colin Hessel, Renske Gahrmann, Whitney Pope, John de Groot, Patrick Wen, Tracy Batchelor, Martin van den Bent, Timothy F Cloughesy
Journal: Neuro-Oncology (2017)

Anti-VEGF therapies remain controversial in the treatment of recurrent GBM. In the current study we demonstrate that recurrent GBM patients with a specific diffusion MR imaging signature have an OS advantage when treated with anti-VEGF therapy at first or second recurrence. These findings were then validated using data from a separate trial. A total of 258 patients with recurrent GBM and diffusion MRI from the monotherapy arms of 5 separate phase II clinical trials were included. Data from 4 trials were used as training data and a fifth for validation: 1) cediranib (NCT00035656); 2) bevacizumab (BRAIN Trial, AVF3708g; NCT00345163); 3) cabozantinib (XL184-201; NCT00704288); 4) aflibercept (VEGF Trap; NCT00369590); and 5) bevacizumab or lomustine (BELOB; NTR1929). Apparent diffusion coefficient (ADC) double-Gaussian histogram analysis was performed prior to therapy to estimate “ADCL”, the mean of the lower ADC distribution. Pre-treatment ADCL, enhancing volume, and clinical variables were tested as independent prognostic factors for OS. The coefficient of variance in double baseline ADCL measurements was 2.5% and did not significantly differ (P=0.454). An ADCL cut-off value of 1.24 um2/ms produced the largest OS differences between patients (HR~0.5), with an ADCL>1.24 um2/ms resulting in better OS. Training and validation data confirmed baseline ADCL as an independent predictive biomarker for OS in all anti-VEGF therapies (P<0.05), but not lomustine (P=0.1455), after accounting for age and baseline enhancing tumor volume. Results suggest pre-treatment diffusion MRI is a predictive imaging biomarker for OS in patients with recurrent GBM treated with anti-VEGF monotherapy at first or second relapse.
EXTH-43. DIFFERENTIATED PHARMACOLOGY OF THE IMIPRIDONE ONC201, THE FIRST SELECTIVE DRD2/3 ANTAGONIST IN CLINICAL NEURO-ONCOLOGY
Authors: Neel Madhukar, Varun Vijay Prabhu, Lakshmi Anantharaman, Chidananda Sulli, Edgar Davidson, Sean Deacon, Rohinton Tarapore, Joseph Rucker, Neil Charter, Benjamin Doranz, Wolfgang Oster, Olivier Elemento, R Benjamin Free, David Sibley, Joshua E Allen
Journal: Neuro-Oncology (2017)

ONC201, founding member of the imipridone class of compounds, has demonstrated evidence of tumor shrinkage along with exceptional safety in recurrent glioblastoma patients. In this study, we identified and characterized a previously unknown binding target of ONC201. BANDIT – a machine learning-based drug target identification platform – predicted that ONC201 would bind with high selectivity to the G-protein coupled receptors (GPCRs) dopamine receptor D2(DRD2) and D3 (DRD3). DRD2 is overexpressed in glioblastoma, controls pro-survival mechanisms, and its antagonism causes pro-apoptotic effects in malignant cells. PathHunter® β-arrestin and cAMP assays determined that ONC201 selectively antagonizes DRD2 and DRD3. Consistent with BANDIT and in contrast to DRD2 blocking antipsychotics, ONC201 did not antagonize other dopamine receptors or other closely related GPCRs with identified endogenous ligands. Schild analyses and radioligand competition assays revealed DRD2 affinities that were consistent with those identified for ONC201 anticancer activity. In accordance with superior selectivity, ONC201 exhibited a wider therapeutic window compared to other antipsychotics. In support of the hypothesis that selectively targeting D2-like receptors yields superior anti-cancer efficacy, combined DRD2/DRD1 inhibition was found to be inferior to DRD2 inhibition alone. ONC201 exhibited a very slow association rate for DRD2 relative to antipsychotics, whereas the dissociation rate was similar to atypical antipsychotics that are better tolerated clinically. Shotgun mutagenesis across 350 amino acids of DRD2 identified 8 residues critical for ONC201-mediated antagonism of DRD2-induced calcium flux. Several residues were not conserved among other dopamine receptors, suggesting a potential role in conferring ONC201 selectivity. Consistent with competitive inhibition, several mutated residues were within the orthosteric binding site (OBS), however, two distal residues were identified outside of the OBS suggesting a secondary binding pocket. In summary, receptor pharmacology of ONC201, the first selective DRD2/3 antagonist in clinical neuro-oncology, may explain its unique selectivity, safety, and anti-cancer activity in clinical trials.
NCMP-12. GLIOMA RELATED EPILEPSY: CLINICAL AND PATHOLOGICAL CORRELATES
Authors: Abdulla Alkuwaiti, Elaine Kobayashi, Marie-Christine Guiot, Kevin Petrecca, Jeffery Hall, Francois Dubeau, Roberto Jose Diaz
Journal: Neuro-Oncology (2017)

The overall incidence of brain tumor related epilepsy among all causes of epilepsies ranges from 4-8%. Epileptic seizures are associated with brain tumor in approximately 30-50% of patients. Glioma is the most common cause of primary brain tumors, contributing nearly 50% of all cases. In high grade glioma seizure frequency is 20-50%, but in low grade it can be up to 90%. There have been multiple publications describing epilepsy frequency in low grade and high-grade glioma but few have described the relationship between seizures and IDH1 R132H mutation. This is an observational retrospective clinical study. Medical records and neuroimaging data were reviewed for all newly diagnosed patients with brain tumor and pathology consisting of oligodendroglioma and astrocytoma WHO grade II and III at the Montreal Neurological Institute and Hospital between 2011 and 2015. IDH1 R132H status was obtained in all tumors and 1p/19q co-deletion was analyzed in all oligodendrogliomas. The details about related seizures were collected, including seizure semiology, timing in relation to surgery, frequency, and antiepileptic medications used. Tumor location was determined by preoperative MRI. There were a total of 103 subjects included in the study. Preoperative seizure frequency was 66% (n=68). There was no association between single or multi-lobe location of tumor and preoperative seizure frequency (n=103, p=0.186). Tumors with mutated IDH1 had a higher rate of preoperative seizure at presentation (74%, n=62 vs 49%, n=37, p=0.007). Seizure freedom at 1 year was increased by gross total resection compared to subtotal resection or biopsy (90%, n= 20 vs 67%, n=55, p=0.049). Presence of an IDH1 mutation, but not tumor location, is associated with higher risk of pre-operative seizure in low and intermediate grade glioma. Extent of surgical resection may influence seizure control at 1 year in patients with low and intermediate grade glioma.
NIMG-07. UNIFYING MAGNETIC RESONANCE IMAGING SIGNATURE OF EGFR PATHWAY ACTIVATION IN GLIOBLASTOMA CONSISTENT WITH UNIFORMLY AGGRESSIVELY INFILTRATION
Authors: Spyridon Bakas, Zev A Binder, Jennifer J D Morrissette, Hamed Akbari, Donald O’Rourke, Christos Davatzikos
Journal: Neuro-Oncology (2017)

Glioblastoma, the most common adult primary malignant brain tumor, has a large degree of inter- and intratumoral radiologic, histologic, and molecular heterogeneity. While various genes are commonly mutated in glioblastoma, the spread of point-mutations within those genes is quite diverse. Epidermal growth factor receptor (EGFR), is found to be mutated or amplified in approximately 60% of glioblastomas, and exhibits a spread of point-mutations accompanying amplification and the EGFR splice variant III (EGFRvIII). EGFRvIII has been shown to increase tumor invasiveness through several downstream pathways, including Akt and Ras/Raf/MAPK. Similar downstream pathway activation has been found in wild-type EGFR amplification in glioblastomas, suggesting a common underlying mechanism for the increased invasion seen in EGFR-activating alterations. This study reports the development of a clinically significant radio-phenotypic signature associated with the activation of the EGFR pathway, irrespective of whether it is through amplification of wild-type EGFR or expression of EGFRvIII or other known activating EGFR point-mutations. This signature is based on a peritumoral heterogeneity index (PHI/φ-index), obtained by comparing the peritumoral perfusion signal in the proximal and distal tissue, relative to the tumor core. A retrospective analysis was conducted on a single-institutional cohort from the University of Pennsylvania with various EGFR alterations and available pre-operative standard and advanced magnetic resonance imaging (MRI). EGFR alterations included tumors with EGFRvIII (n=42), wild-type EGFR amplification (n=6), and the most common EGFR point-mutations (n=25) (i.e. R108K, A289D/T/V, G598V). Lower PHI values, consistent with uniformly aggressively infiltrating tumors throughout the peritumoral edema, was found on tumors with EGFR alterations compared to EGFR non-mutated and non-amplified control cases (n=100). The resulted MRI signature of this study, suggestive of increased tumor invasiveness, matched the anticipated biological impact of the EGFR alterations and represents a marker of EGFR pathway activation in glioblastoma, potentially useful for monitoring targeted treatment-response along this pathway.
TMIC-35. LONGITUDINAL ALTERATIONS OF CORTICAL ACTIVITY DURING GLIOMA PROGRESSION IN A MOUSE MODEL
Authors: Elena Tantillo, Chiara Cerri, Chiara Maria Mazzanti, Mario Costa, Matteo Caleo
Journal: Neuro-Oncology (2017)

Gliomas are the most common primary tumors of the central nervous system. A better understanding of the bidirectional interactions between glioma cells and surrounding brain tissue is required for the development of novel therapies. A successful brain tumor treatment should indeed aim at halting tumor growth and at the same time protecting neuronal cells to prevent functional deficits and cognitive deterioration. Currently, very little is known about the functional status of peritumoral tissues during glioma progression. We transplanted GL261 cells into the primary visual cortex of syngeneic C57JBl6 mice and we performed chronic recordings of visual evoked potentials (VEPs) and local field potentials (LFPs) in awake, head-fixed mice. A subset of mice with sham surgery were used as controls. The visual cortex was chosen as a recording site since it can be activated by physiological stimuli and for the availability of well established parameters to evaluate its functionality. A detailed analysis of VEPs and LFPs was performed. We observed an initial progressive increase in VEP amplitude, indicative of stimulus-dependent response potentiation (SRP). In glioma-bearing mice, the initial phase of SRP was followed by rapid decay and deterioration of visual responses, that completely disappeared by day 25 after cell transplant. LFPs recordings revealed the occurrence of seizures in a subset of the glioma-bearing animals. Alterations of the LFP power spectra were detected, with an increase in slow activity (delta band) during glioma development. Our findings indicate the feasibility of longitudinal monitoring neural activity during glioma progression to better understand the interaction of tumor cells with the brain microenvironment. These data provide a set of quantitative parameters to measure dysfunction in peritumoral regions during glioma growth, and assess the impact of radiotherapy, chemotherapy, and antiepileptic drugs on neuronal activity in glioma-bearing animals.
P1.02-011 XRCC6BP1: A Key Player in the DNA Repair of Cisplatin Resistant NSCLC Cells
Authors: M. Barr, S. Singh, R. Farrell, E. Foley, Y. He, L. Brady, V. Young, R. Ryan, S. Nicholson, N. Leonard, S. Cuffe, S. Finn
Journal: Journal of Thoracic Oncology (2017)
Abstract 20905: The Force-Displacement Relationship in Commonly Used Resuscitation Manikins: Not Very Human
Authors: Jakob E Thomsen, Mathilde Stærk, Bo Løfgren
Journal: Circulation (2017)

Introduction: Manikins are widely used for CPR training and designed to simulate a human in cardiac arrest. Previous studies show a non-linear force-displacement relationship in the human chest. This may not be the case for resuscitation manikins. The aim of this study was to investigate the force-displacement relationship in commonly used resuscitation manikins. Methods: Commonly used infant and adult manikins for resuscitation training were included in the study. Manikins were tested by placing them in a material testing machine (ProLine Z050, Zwick/Roell, Ulm, Germany). A piston was placed on lower half of the sternum of the manikin. The testing machine applied a constant growing force downwards on the manikin chest while recording the force-displacement relationship. The test was stopped when either the manikin was nearly fully compressed or the displacement exceeded 7 cm. On manikins with adjustable compliance of the thorax, the medium setting was used. The force needed to achieve the recommended compression depth i.e. 3 cm and 5 cm were compared for infant and adult manikins respectively. Results: Seven different resuscitation manikins were included in the study; two infant manikins: Resusci Infant (Laerdal) and CPR Anytime® Infant (inflatable; American Heart Association) and five adult manikins: Mini Anne (inflatable), Little Anne®, Resusci Anne, Resusci Anne Advanced(Laerdal) and Ambu® Man (Ambu). Infant manikins required a force of 57 N and 34 N to compress the chest 3 cm. The force required to compress the adult manikins to a depth of 5 cm ranged from 195 N to 543 N. The force-displacement curve is shown in the Figure. Conclusions: Four out of five adult resuscitation manikins and one infant manikin had a nearly linear force-displacement curve different from the human chest. The Mini Anne and Resusci Infant showed a non-linear curve more like the human chest. The force needed to compress the chest to the recommended chest compression depth varied between manikins.
Management of breakthrough cancer pain in patients with oral mucositis
Authors: S. Tolu, E. Lai, V. Impera, G. Pusole, A. Pretta, N. Liscia, S. Camera, A. Cubeddu, R. Mascia, A.G. Pireddu, M. Dessì, M. Puzzoni, L. Demurtas, P. Ziranu, V. Pusceddu, E. Massa, C. Madeddu, F. Atzori, G. Astara, M. Scartozzi
Journal: Annals of Oncology (2017)
P1.01-070 BIW-8962, an Anti-GM2 Ganglioside Monoclonal Antibody, in Advanced/Recurrent Lung Cancer: A Phase I/II Study
Authors: J. Lee, J. Kim, S. Kim, J. Kang, D.H. Lee, B.C. Cho, N. Shiraishi, V. Strout, K. Park
Journal: Journal of Thoracic Oncology (2017)
MA 17.06 Safety Data from Randomized Phase II Study of CDDP+S-1 vs CDDP+PEM Combined with TRT for Locally Advanced Non-Squamous NSCLC
Authors: A. Ono, T. Takahashi, S. Niho, T. Yoshida, T. Akimoto, K. Sakamaki, T. Seto, M. Nishio, N. Yamamoto, T. Hida, H. Okamoto, T. Kurata, M. Satouchi, K. Goto, T. Yamanaka, Y. Ohe
Journal: Journal of Thoracic Oncology (2017)
P2.03-044 OSCILLATE - Phase 2 Trial of Alternating Osimertinib with Gefitinib in Patients with EGFR-T790M Mutation Positive Advanced NSCLC
Authors: B. Solomon, P. Kok, A. Livingstone, S. Yip, C. Brown, S. Dawson, S. Wong, N. Pavlakis, M. Stockler
Journal: Journal of Thoracic Oncology (2017)
The regorafenib issue: focus on efficacy and safety in pre-treated metastatic colorectal cancer from a real world experience
Authors: F. Daniel, E. Bannò, L. Belluomini, L.R. Martella, F. Lancia, I. Toma, A. Moretti, G. Mentrasti, I. Carandina, M. Marzola, A. Frassoldati
Journal: Annals of Oncology (2017)
Circulación clonal de Salmonella enterica serotipo Heidelberg en Italia
Authors: C Mammina, M Talini, M Pontello, A M Di Noto, A Nastasi
Journal: Eurosurveillance (2003)

Se ha realizado en Italia un estudio de las caracteristicas fenotipicas y geneticas de 21 cepas de Salmonella serotipo Heidelberg aisladas en los anos 1999 - 2003 de distintos origenes. Como marcadores epidemiologicos se utilizaron patrones de sensibilidad, el analisis del perfil plasmidico y PFGE. 
Aunque se han detectado patrones de resistencia a los farmacos y perfiles plasmidicos no homogeneos, los patrones PFGE sugieren la hipotesis de una diseminacion clonal nacional de este serotipo asociado a las aves de corral.