tbuckley/cabot-search huggingface dataset:
CMET-23. INITIAL CLINICAL EXPERIENCE WITH BRAINLAB ELEMENTS FOR INTRACRANIAL METASTASES
Authors: Andrew Song, Haisong Liu, Jun Li, David Andrews, Wenyin Shi
Journal: Neuro-Oncology (2017)

Brainlab Elements Automatic Brain Metastases Planning is a new technology for automated optimized planning using mono-isocenter. We reviewed our initial clinical experience. From August 2015 to January 2017, we identified 40 patients treated with Elements for ICM. We examined the electronic medical records to assess patient demographics, primary disease status, time to progression (TTP), overall survival (OS), and toxicities. We reviewed pre- and post-SRS MRI brain imaging to determine local and regional intracranial control, as well as dosimetry and treatment plans evaluating parameters associated with each SRS. Of the 40 patients, 19 (47.5%) were males and 21 (52.5%) were females. Primary cancers included 21 non-small cell lung (52.5%), 8 melanoma (20%), 7 breast (17.5%), and one each of colon, esophageal, testicular, and unknown primary. Median age of patients was 65 years old (range 27–83). Median follow-up was 204 days. Median KPS was 90 (60–100). Median GPA was 2 (0.5–4). Median number of lesions treated was 3 (2–10). Median maximum dimension of lesions was 1.16 cm (0.57–4.33) with individual lesion volume treated was 0.494 cc (0.065–12.972) and total lesion volume was 4.227 cc (0.497–20.026). Median dose was 21 Gy (15–24). No acute (<1 month from SRS) toxicities were reported. Long term toxicities included one patient with Grade 1 headache and two patients with Grade 2 radionecrosis. OS at 6 months and 1 year, were 69.63% and 35.65% respectively, with median survival 297 days. Local control at 6 months was 86.57% and 30.36% at 1 year, with median TTP 309 days. Intracranial control at 6 months was 52.32% and 14.99% at 1 year, with median TTP 203 days. Elements provides a new planning platform to treat multiple ICM in a safe and efficient manner. Longer term follow-up with a larger patient base is warranted to enhance treatment optimization.
ANGI-16. NOTCH SIGNALING IN BEVACIZUMAB-INDUCED VASCULAR NORMALIZATION IN GLIOBLASTOMA
Authors: Norihiko Saito, Kazuya Aoki, Nozomi Hirai, Satoshi Fujita, Junya Iwama, Haruo Nakayama, Morito Hayashi, Keisuke Ito, Takatoshi Sakurai, Satoshi Iwabuchi
Journal: Neuro-Oncology (2017)

Tumor angiogenesis occurs in the setting of a defective vasculature, which is associated with increased vascular permeability and enhanced tumor permeability. Bevacizumab is used to treat malignant glioma and was found to reduce microvascular density and prune abnormal tumor microvessels. Using electron microscopic observation of two autopsy cases, we investigated the effects of blood vessel normalization in glioblastomas treated with bevacizumab. Notch-1 and SMA immunostaining were used to compare initial surgical specimens with postmortem specimens obtained after bevacizumab treatment. Postmortem samples showed marked proliferation of SMA-positive cells (pericytes) in tumor vessels and marked proliferation of Notch-1–positive cells around vessels. Electron microscopic images confirmed the presence of pericytes surrounding the vascular endothelium. These findings suggest that bevacizumab treatment promotes vascular normalization by recruiting mature pericytes. Next, we investigated the effects of bevacizumab on VEGF inhibition in glioma stem cells. Bevacizumab treatment attenuated activation of VEGFR2 and increased Notch signaling expression. VEGF inhibition by bevacizumab treatment attenuated proliferation and self-renewal of glioma stem cells and induced endothelial and pericyte differentiation. In tumor angiogenesis, vascular endothelial growth factor induces sprouting angiogenesis and recruitment of vascular endothelial cells such as tip cells, stalk cells, and phalanx cells. Fully mature phalanx cells are in close contact with pericytes. Our results suggest that bevacizumab treatment induces glioma stem cells to differentiate to endothelium and pericytes. These mechanisms might be important in normalizing tumor vasculature after bevacizumab treatment and could be useful in improving the effectiveness of current glioma therapy.
Prognostic impact of hyponatremia in patients affected by advanced non-small cell lung cancer (NSCLC) with bone metastases (BMs)
Authors: S. Rinaldi, M. Santoni, G. Armento, M. Torniai, F. Morgese, G. Leoni, I. Fiordoliva, V. Paolucci, A. Savini, A. Onofri, D. Santini, R. Berardi
Journal: Annals of Oncology (2017)
MA 13.02 Comprehensive Genetic Analysis Related to PD-L1 Expression in Early-stage Lung Squamous Cell Carcinoma
Authors: H. Yu, Z. Chen, K. Ballman, M. Watson, R. Govindan, D. Beer, R. Bueno, L. Chirieac, M. Chui, W. Franklin, D.R. Gandara, C. Genova, M. Joshi, D. Merrick, W. Richards, C. Rivard, F. Shepherd, T. Sporn, M. Tsao, K. Brovsky, A. Bokhoven, D. Harpole, F.R. Hirsch
Journal: Journal of Thoracic Oncology (2017)
RARE-17. IMPACT OF SURGERY, ADJUVANT TREATMENT AND OTHER PROGNOSTIC FACTORS IN THE MANAGEMENT OF PLEOMORPHIC XANTHOASTROCYTOMA: AN INDIVIDUAL PATIENT DATA ANALYSIS OF 328 CASES
Authors: Supriya Mallick, Rony Benson, Prashanth Giridhar, Goura Kishor Rath
Journal: Neuro-Oncology (2017)

This systematic review and individual patient’s data analysis was aimed to look into “optimum extent of surgery”, “role of adjuvant therapy” in patients with Xanthoastrocytoma. A thorough search of the PubMed and Google was made to find all possible publications. Data of 328 individual patients from 149 publications were retrieved. Median age 33years (4.5-75years). 46.3% patients presented with seizure. 119 (39.8%) had tumor in temporal and 10.7 % in frontal lobe. 148 (57.8%) patients underwent GTR and 81 (31.6%) STR. 175 (79.2%) patients had grade II tumor and 20.8% patients grade III tumor. Median Ki 67, 5.5 (1-33.2). In 15 patients (60%) out of 25 available cases BRAF mutation was noted. Adjuvant radiation was delivered in 67 (27.7%) patients. Estimated median PFS was 48.3 months. In univariate analysis younger patients (≤20 years) had better PFS compared to elder [103.2 vs 36 months (p= .013]. Patients with GTR and grade II tumor had better PFS than STR and grade III tumor [84 vs14 months; p=0.001]; [48 vs 11.7 months p=0.000]. Ki 67 index ≤5% conferred better PFS [144 vs 17 months; p=0.250]. Estimated median OS was 209.0 months. In univariate analysis younger patients (≤20 years) found to have better OS [300 vs 209 months; p=.001]. Patients with a GTR and grade II tumor had a significantly better OS than STR (p=0.001) or with a grade III tumor [209 vs 49 months; p=0.001]. A lower Ki 67 index of ≤5% conferred a better OS [168 vs 49 months; p=0.08]. OS was significantly worse for patients treated with adjuvant radiation (p=0.007). Patients with younger age, GTR, grade II tumor and lower MIB have a better survival.
IMMU-43. COMPLEMENT 1 INACTIVATOR IS UPREGULATED IN GLIOBLASTOMAS
Authors: Karolina Förnvik, Aida Maddahi, Oscar Persson, Kurt Osther, Leif G Salford, Henrietta Nittby Redebrandt
Journal: Neuro-Oncology (2017)

A major problem regarding glioblastomas is the capacity of glioma cells to inactivate the body’s immune response. The complement system acts as a functional bridge between the innate and adaptive immune response. Previously, it was thought that the complement system was upregulated in glioblastomas. However, only downstream components were studied. Here, we focus on C1, the initiating step of the complement cascade. We here show that the C1 inactivator (C1IA) is upregulated in glioblastomas. The main function of complement 1 inactivator (C1-IA) is to inhibit activation of the complement system through the classical pathway, by irreversibly binding to and inactivating of C1r and C1s proteases in the C1 complex of the classical pathway. The C1IA upregulation is seen both on gene and protein levels, as seen in data from a publicly available database and our own mRNA material from glioblastoma patients. Furthermore, we demonstrated the presence of C1-IA in vitro by using immunohistochemistry on glioma cells from both humans and rats. Finally, we could demonstrate a significantly increased survival in vivo in animals inoculated intracerebrally with glioma cells pre-coated with C1-IA antibodies as compared to control animals. We tested both human anti-C1IA antibodies, and rat anti-C1IA antibodies, and could demonstrate the same pattern as compared to control animals. We could also see that the protein structure is quite similar in human C1IA and rat C1IA. Taken together, our findings indicate that overexpression of C1-IA is present in glioblastomas and that it is an interesting target to explore further.
Sleep Apnea and Cardiovascular Disease
Authors: Luciano F. Drager, R. Doug McEvoy, Ferran Barbe, Geraldo Lorenzi-Filho, Susan Redline
Journal: Circulation (2017)

Emerging research highlights the complex interrelationships between sleep-disordered breathing and cardiovascular disease, presenting clinical and research opportunities as well as challenges. Patients presenting to cardiology clinics have a high prevalence of obstructive and central sleep apnea associated with Cheyne-Stokes respiration. Multiple mechanisms have been identified by which sleep disturbances adversely affect cardiovascular structure and function. Epidemiological research indicates that obstructive sleep apnea is associated with increases in the incidence and progression of coronary heart disease, heart failure, stroke, and atrial fibrillation. Central sleep apnea associated with Cheyne-Stokes respiration predicts incident heart failure and atrial fibrillation; among patients with heart failure, it strongly predicts mortality. Thus, a strong literature provides the mechanistic and empirical bases for considering obstructive sleep apnea and central sleep apnea associated with Cheyne-Stokes respiration as potentially modifiable risk factors for cardiovascular disease. Data from small trials provide evidence that treatment of obstructive sleep apnea with continuous positive airway pressure improves not only patient-reported outcomes such as sleepiness, quality of life, and mood but also intermediate cardiovascular end points such as blood pressure, cardiac ejection fraction, vascular parameters, and arrhythmias. However, data from large-scale randomized controlled trials do not currently support a role for positive pressure therapies for reducing cardiovascular mortality. The results of 2 recent large randomized controlled trials, published in 2015 and 2016, raise questions about the effectiveness of pressure therapies in reducing clinical end points, although 1 trial supported the beneficial effect of continuous positive airway pressure on quality of life, mood, and work absenteeism. This review provides a contextual framework for interpreting the results of recent studies, key clinical messages, and suggestions for future sleep and cardiovascular research, which include further consideration of individual risk factors, use of existing and new multimodality therapies that also address adherence, and implementation of trials that are sufficiently powered to target end points and to support subgroup analyses. These goals may best be addressed through strengthening collaboration among the cardiology, sleep medicine, and clinical trial communities.
NIMG-78. FIRST TIME CORRELATION OF FET PET, MRI AND POST-MORTEM WHOLE-BRAIN HISTOPATHOLOGY IN A PROGRESSIVE GLIOBLASTOMA
Authors: Philipp Lohmann, Marc D Piroth, Bernd Sellhaus, Stefanie Geisler, Ana-Maria Oros-Peusquens, Hartmut Mohlberg, Katrin Amunts, Nadim J Shah, Norbert Galldiks, Karl-Josef Langen
Journal: Neuro-Oncology (2017)

Amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) provides important additional information on the extent of viable tumor tissue of glioblastoma compared with MRI. Especially after radiochemotherapy, progression of contrast enhancement in MRI can be equivocal and may represent either true tumor progression or treatment-related changes. We present the first case comparing post-mortem whole-brain histopathology in progressive glioblastoma with dynamic in vivo FET PET and MRI. A 61-year-old glioblastoma patient underwent initially partial resection and died eleven weeks after completion of chemoradiation with concurrent temozolomide. Three days before the patient died, a follow-up FET PET and MRI scan indicated local tumor progression within the irradiation field. An autopsy was performed at 48 h hours after death and the tumor bearing brain was preserved. After fixation in formalin and paraffin embedding, the brain tissue was cut into 3500 coronal sections (20 micrometers). Representative sections were stained using GFAP and cresyl violet. An experienced neuropathologist identified areas of neoplastic tissue, astrogliosis and necrosis. In vivo FET PET, MRI and histopathology were co-registered and compared by three experienced physicians. Increased FET uptake (tumor-to-brain ratio = 2.3) in the area of equivocal contrast enhancement on MRI correlated very well with vital tumor cells and showed tracer kinetics typical for malignant gliomas (early peak followed by constant descent). An area of reactive astrogliosis showed only moderate FET uptake (tumor-to-brain ratio = 1.5) and tracer kinetics usually observed in benign lesions (constantly increasing). Necrotic areas showed neither enhanced FET uptake nor contrast enhancement in MRI. This case report documents for the first time the correct imaging of a progressive glioblastoma by FET PET, thereby confirming findings from previous studies. FET PET significantly contributes to the correct identification of neoplastic tissue and, thus, to a better differentiation of tumor progression and treatment-related changes.
Quality of life in the GLARIUS trial randomizing bevacizumab/irinotecan versus temozolomide in newly diagnosed, MGMT-nonmethylated glioblastoma
Authors: Niklas Schäfer, Martin Proescholdt, Joachim P Steinbach, Astrid Weyerbrock, Peter Hau, Oliver Grauer, Roland Goldbrunner, Franziska Friedrich, Veit Rohde, Florian Ringel, Uwe Schlegel, Michael Sabel, Michael W Ronellenfitsch, Martin Uhl, Stefan Grau, Mathias Hänel, Oliver Schnell, Dietmar Krex, Peter Vajkoczy, Ghazaleh Tabatabai, Frederic Mack, Christina Schaub, Theophilos Tzaridis, Michael Nießen, Sied Kebir, Barbara Leutgeb, Horst Urbach, Claus Belka, Walter Stummer, Martin Glas, Ulrich Herrlinger
Journal: Neuro-Oncology (2017)

The GLARIUS trial, which investigated the efficacy of bevacizumab (BEV)/irinotecan (IRI) compared with standard temozolomide in the first-line therapy of O6-methylguanine-DNA methyltransferase (MGMT)-nonmethylated glioblastoma, showed that progression-free survival was significantly prolonged by BEV/IRI, while overall survival was similar in both arms. The present report focuses on quality of life (QoL) and Karnofsky performance score (KPS) during the whole course of the disease.Patients (n = 170) received standard radiotherapy and were randomized (2:1) for BEV/IRI or standard temozolomide. At least every 3 months KPS was determined and QoL was measured using the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life and 20-item Brain Neoplasm questionnaires. A generalized estimating equation (GEE) model evaluated differences in the course of QoL and KPS over time. Also, the time to first deterioration and the time to postprogression deterioration were analyzed separately.In all dimensions of QoL and KPS, GEE analyses and time to first deterioration analyses did not detect significant differences between the treatment arms. At progression, 82% of patients receiving second-line therapy in the standard arm received BEV second-line therapy. For the dimensions of motor dysfunction and headaches, time to postprogression deterioration was prolonged in the standard arm receiving crossover second-line BEV in the vast majority of patients at the time of evaluation.GLARIUS did not find indications for a BEV-induced detrimental effect on QoL in first-line therapy of MGMT-nonmethylated GBM patients. Moreover, GLARIUS provided some indirect corroborative data supporting the notion that BEV may have beneficial effects upon QoL in relapsed GBM.
P2.13-008 Lung Cancer Screening Improves Mortality: Examining Screening Patterns in an Urban Underserved Community
Authors: C. Su, A. Bhargava, C. Shah, B. Halmos, R. Gucalp, S. Packer, N. Ohri, L. Haramati, R. Perez-Soler, H. Cheng
Journal: Journal of Thoracic Oncology (2017)
Association of Cardiac Hemodynamic Factors With Severity of White Matter Hyperintensities in Chronic Valvular Heart Disease
Authors: Woo-Jin Lee, Keun-Hwa Jung, Young Jin Ryu, Jeong-Min Kim, Soon-Tae Lee, Kon Chu, Manho Kim, Sang Kun Lee, Jae-Kyu Roh
Journal: JAMA Neurology (2017)

The cerebral white matter hyperintensity (WMH) is frequently noted in patients with chronic heart disease. Long-term alteration of cardiac hemodynamics might have an influence on the mechanism of cerebral WMH.To investigate the association between chronically altered cardiac hemodynamics and severity of cerebral WMH in patients with chronic valvular heart disease.This cross-sectional analysis identified 303 consecutive patients at a tertiary referral center between 2008 and 2016 who were 50 years or older, and diagnosed with severe chronic valvular heart disease and underwent cardiac catherization, echocardiography, and received brain magnetic resonance imaging. Among these patients, 71 with other demonstrated cardiac disease, central nervous system disease, and/or without sufficient catheterization data were excluded, and the remaining 232 patients were included in further analyses.The site and mechanism of valve diseases, as well as clinical and medication profiles, were reviewed. Cardiac catheterization parameters such as right atrial (RA) mean pressure, right ventricular pressure, and aortic mean pressure were obtained. Comprehensive echocardiographic hemodynamic markers such as left ventricular (LV) ejection fraction, LV mass index, LV end diastolic volume, cardiac index, and E/e' ratio were also obtained.White matter hyperintensity volume was quantitatively evaluated using volumetric analysis.This study included 232 patients (103 men [44.4%] and 129 women [55.6%]; mean [SD] (range) age, 65.6 [8.8] (51-88) years) in the final analysis. The mean (SD) WMH volume was 5.93 (7.14) mL (median [interquartile range], 4.33 [1.33-8.62] mL), and mean (SD) RA pressure was 10.0 (4.7) mm Hg. From the catheterization data, 147 patients (63.4%) were classified as having a disease involving the mitral valve; 93 (40.1%), aortic valve; 37 (15.9%), tricuspid valve; and 4 (1.7%), pulmonary valve. In multivariate linear regression analysis, adjusting the type and mechanism of valve disease and clinical, echocardiographic, and/or other catheterization parameters, WMH volume was linearly associated with mean RA pressure (B coefficient, 0.702; 95% CI, 0.373-1.031; P = .001), along with age (B coefficient, 0.145; 95% CI, 0.029-0.261; P = .01) and mean aortic pressure (B coefficient, 0.112; 95% CI, 0.034-0.190; P = .005).Mean RA pressure was independently associated with the WMH volume in chronic valvular heart disease. Chronically altered RA hemodynamics might have a distinct influence on the pathomechanism underlying the development of WMH.
New artificial immunological systems algorithms useful to investigate chromosomal high throughtput data
Authors: Stefania Tommasi, Filippo Menolascina, Vitoantonio Bevilacqua, Roberto Alves, Giuseppe Mastronardi, Angelo Paradiso
Journal: Cancer Research (2008)

1639   Many biological and clinical questions can be answered by molecular tests producing high density data. However, the results are often differently interpreted depending on the algorithm used. In particular, Array Comparative Genomic Hybridization (aCGH) platform has been used to investigate chromosomal alterations, in terms of region gain or loss, characterizing peculiar tumor phenotypes, such as histological types or steroid receptor expression. The enormous complexity of the DNA alterations in cancer genomes has been demonstrated to be consistent with a non random patterns of copy number alterations in human cancer.  With the present work we would like to verify the possibility to use a new class of algorithm based on Artificial Immune System (AIS) paradigm to elucidate the biological dynamics of cancerous processes using a novel fuzzy rule induction system for data mining (IFRAIS). It is the first time that this algorithm has been used for a biological purpose.  A high-resolution array Comparative Genomic Hybridization based on 2464 BAC clones (HunArray2.0, UCSF Comprehensive Cancer Center Microarray Core), has been carried out as previously described (Pinkel and Albertson, 2005; Fridlyand 2006). We analyze these data with already validated algorithms as J48, Ant Miner and GEP and with IFRAIS with the aim to extrapolate rules classifying breast cancer patients with respect to oestrogen receptor status (ER+ vs ER-) and familiarity (familial vs sporadic). Competitive results have been obtained using IFRAIS with respect to the other 3 methods in terms of accuracy (88,95%) and k-statistic (0,648). Furthermore, a strong correlation of Gene Ontology Terms discovered by the 4 top performing algorithms has been observed. In particular, the attention has to be focused in FER role in ER status determination, while, 3 rules have been extrapolated to define familial breast cancer and 5 to define sporadic. In conclusion, the results showed that AIS based classifier returned results, in terms of accuracy and kappa statistic quite comparable with the ones that characterized best performing tree classifiers. These results seem to encourage further studies on the employment of such systems in these context. AIS systems seem to be their ease in context characterized by high dimensional data and complex information distribution.
P3.01-059 First Experience with Osimertinib in Patients with Newly Developed T790M Mutation Previously Treated with EGFR – TKIs in Croatia
Authors: M. Jakopovic, L. Bitar, F. Seiwerth, S. Plestina, S. Kukulj, S. Seiwerth, M. Misic, G. Redzepi, M. Samarzija
Journal: Journal of Thoracic Oncology (2017)
GENE-27. DIFFERENTIAL LEVELS OF H3K27me3 AT THE EfnA5 PROMOTER ARE CONTROLLED BY Bmi1 THROUGH MODULATION OF JmjD3 IN GLIOBLASTOMA
Authors: Loredana Guglielmi, Barbara Ricci, Michael Barnes, Silvia Marino
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme (GBM) is the most common malignant adult intrinsic brain tumour. Recent studies on gliomagenesis have provided new insights into the genomic and epigenomic landscape of this disease. Fine-tuned regulation of expression of key genes involved in several cellular processes, such as proliferation and migration, has proved to be essential in defining the biological characteristics that are specific of glioblastoma stem-like cells (GSCs) as compared to neural stem cells (NSCs). We have identified EfnA5, a member of the ephrin-A subclass of ephrin ligands, as a direct target of the polycomb complex protein Bmi1 in a murine GSC model in genome wide transcriptomic and histone modification analysis. We found evidences that a similar epigenetic signature is also present in human GSCs, according to publicly available ChIP-seq data. To further investigate the mechanistic relationship between Bmi1 and EfnA5, we performed ChIP-on-tissue assay which allowed us to detect and monitor the repressive histone mark H3K27me3 at the EfnA5 locus at single-cell level. We show that Bmi1 regulates the levels of the H3K27me3 at EfnA5 promoter region via repression of the demethylase JmjD3. These findings raise the possibility that pharmacological targeting of either EfnA5 or JmjD3 may be of particular interest for GBM overexpressing Bmi1.