tbuckley/cabot-search huggingface dataset:
Abstract P189: Cardiovascular Risk Factors in Adolescence and Young Adulthood Predict Carotid Intima-Media Thickness in Early and Middle Adult Life
Authors: Amber L Fyfe-Johnson, Julia Steinberger, Alan R Sinaiko, Alvaro Alonso, Donald R Dengel, David R Jacobs
Journal: Circulation (2015)

Introduction: Cardiovascular (CV) risk factors measured in childhood and adulthood are positively associated with increased carotid intima-media thickness (cIMT) later in life. In particular, body mass index (BMI), systolic blood pressure (SBP), and lipids are implicated. However, questions remain regarding prediction of cIMT from adolescent and young adult CV risk factors. Hypothesis: CV risk factors are positively associated with young adult and early middle age cIMT thickening, both cross-sectionally and longitudinally. Methods: CV risk factors (BMI, SBP, metabolic syndrome [MetS, mean of CV risk factor z-scores]) were measured in two pediatric cohort studies. The Insulin Study measured CV risk factors in 305 adolescents at mean ages 15 and 22 years, with cIMT measured at mean age 22 years. The Prevention of High Blood Pressure in Children Study measured CV risk factors in 444 individuals at mean ages 24 and 38 years, with cIMT measured at mean age 38 years. Predictors were categorized into quartiles; cIMT was measured by ultrasonography. Linear regression models were used to predict cIMT and adjust for potential confounding variables. Differences between risk factor quartile 4 and quartile 1 (Q4-Q1) were used in analyses, with a p -test for trend based on continuous predictors. Results: Positive cross sectional associations were found between CV risk factors at ages 24 and 38 and cIMT at 38 (Table). Positive longitudinal associations were found between BMI (Q4-Q1: 0.024 mm, p=0.0001) and MetS score (Q4-Q1: 0.019 mm, p=0.004) at age 15 and cIMT at age 22, and between BMI (Q4-Q1: 0.045 mm, p=0.01) and MetS score (Q4-Q1: 0.048 mm, p&lt;0.0001) at age 24 and cIMT at age 38 (Table). SBP at ages 24 and 38 was predictive of cIMT at age 38. Conclusions: These findings suggest that CV risk factors beginning in adolescence predict cIMT thickening in young adulthood, and this predictive association continues into middle age. This supports early identification of CV risk, and initiation of preventive strategies to reduce early CV disease.
ACTR-01. RETROSPECTIVE ANALYSIS OF OLIGODENDROGLIOMA TREATMENT AT A SINGLE INSTITUTION
Authors: Frank J Barbiero, Kevin Becker, Joachim M Baehring
Journal: Neuro-Oncology (2017)

Recently published results of randomized prospective clinical trials have demonstrated benefit from sequential radiation and chemotherapy after surgery for oligodendroglial tumors (RTOG 9802, 9402; EORTC 26951). We aimed to investigate whether such a benefit could be demonstrated in a retrospective cohort treated at our institution. Patients were identified from the quality control database in the Section of Neuro-Oncology, Yale Cancer Center. Histologic, clinical, imaging, treatment, and outcome data was reviewed. Patients who were 18 to 39 years old and had undergone gross total resection of a WHO II lesion were deemed low-risk (LR). High-risk patients were those ≥40 years old or who had undergone an incomplete resection or those with anaplastic tumors. Primary outcome measure is progression-free survival (PFS). Secondary outcome measure is overall survival (OS). PFS and OS are analyzed in high-risk patients who at initial diagnosis received sequential therapy (HR-SEQ) compared to individuals who only underwent surgery alone or combined with one adjuvant treatment modality (HR-DEL). Survival estimates are based on Kaplan Meier method and survival distributions are compared using the log-rank test. We identified 150 consecutive biopsy-confirmed oligodendroglioma cases who were treated at Yale Cancer Center between 2002 and 2016. Forty-one patients (27%) are deceased. Thirty patients were considered low risk (1p/19q intact, n=14; co-deletion, n=14; 1p-deleted, n=2). Amongst the high-risk patients, 99 were in the SEQ group (1p/19q intact, n=46; co-deletion, n=47; 1p-deleted, n=2; 19q-deleted, n=4) and 21 in the DEL group (1p/19q intact, n=9; co-deletion, n=8; 1p-deleted, n=3; 19q-deleted, n=1). Median OS was 15.1 years for LR, 6.75 years for HR-SEQ, and 16.95 years for HR-DEL. PFS and subgroup analysis based on molecular markers is ongoing. We reserve our conclusions until the analysis is complete. The cohort is likely too small for detailed subgroup analysis.
P3.02-018 Patients Harboring ALK Rearrangement Adenocarcinoma after Acquired Resistance to Crizotinib and Transformation to SCLC: A Case Report
Authors: W. Wang, C. Xu, Y. Zhu, X. Liao, W. Zhuang, K. Du, R. Chen, Y. Chen, G. Chen, M. Fang
Journal: Journal of Thoracic Oncology (2017)
Abstract 20076: Short-Term and Long-Term Mortality Rates in Patients With and Without Valvular Heart Disease Who Have Acute Decompensated Heart Failure: An Atherosclerosis Risk in Communities (ARIC) Study
Authors: Aamir Husain, Melissa Caughey, Michael Sola, Patricia P Chang, Cassandra J Ramm, Michael Yeung, Amil M Shah, Kunihiro Matsushita, Dalane Kitzman, John P Vavalle
Journal: Circulation (2016)

Introduction:  Valvular heart disease remains an important cause of heart failure. Studies comparing acute decompensated heart failure (ADHF) associated with valvular disease to other forms of ADHF are limited. We compared mortality rates of patients with acute decompensated valvular heart failure (ADVHF) to those with non-valvular ADHF (ADnVHF).   Hypothesis:  Mortality differs between ADVHF and ADnVHF.   Methods:  The Atherosclerosis Risk in Communities (ARIC) study conducted surveillance of hospitalized ADHF patients age ≥55 years in 4 U.S. communities starting in 2005. ADHF hospitalizations were validated by standardized physician review. The prevalence of at least moderate mitral and aortic valvular disease was quantified using in-hospital echocardiograms. In-hospital, 28-day, and 1-year mortality were compared between ADVHF and ADnVHF using logistic regression and adjusted for demographics.   Results:  From 2005 to 2011, a weighted sample of 15,397 patients was hospitalized for ADHF and had echocardiography data. The ADVHF group was predominantly female (55%), Caucasian (70%), and had a mean age of 76 ± 0.2 yrs. After multivariate adjustment, in-hospital mortality was 30% lower for ADVHF patients compared to those with ADnVHF (OR 0.7, 95% CI 0.5 to 1.0). At 28 days, mortality rates were similar. At 1 year, however, mortality rates were 20% higher for the ADVHF group (OR 1.2, 95% CI 1.0 to 14) (Figure 1).   Conclusions:  Valvular heart disease is associated with increased risk for 1-year mortality in those hospitalized with heart failure, despite a lower in-hospital mortality in our sample. This suggests that patients with ADVHF have a worse long-term prognosis than those with ADnVHF and may benefit from more intensive follow-up care and aggressive therapy after hospital discharge.
ATIM-03. BIOMARKER ANALYSIS SUPPORTS THE VB-111 DUAL MECHANISM OF ACTION
Authors: Aleksandra Gruslova, Yichu Liu, Patrick Wen, Katherine B Peters, James Vredenburgh, Felix Bokstein, Deborah T Blumenthal, Yael Cohen, Itzhak Mendel, Eyal Breitbart, Andrew Brenner
Journal: Neuro-Oncology (2017)

VB-111 (Ofranergene Obadenovec) is non-integrating, non-replicating, Adeno 5 vector which targets the vasculature through induction of endothelial apoptosis. Our prior phase 2 study has shown a nearly doubling of overall survival (OS) in recurrent glioblastoma (rGBM) (59v32 weeks), and our pivotal phase 3 GLOBE study is fully accrued. To better understand any predictors of benefit and better define alternative mechanisms of action we assess both molecular and radiographic biomarkers of response. Tumor volumes were determined from T1-post and FLAIR T2 weighted images, and values extracted from ROIs of ADC, MTT, standardized rCBV maps. Baseline serum and 6h post infusion underwent cytokine profiling using a luminex array. To delineate the source of cytokines orthotopic U251 tumors were treated with VB-111 or control, resected, microglia (CD11b) and T cells (CD3) sorted, and individually cocultured with activated splenocytes. In the univariate cox analysis, baseline srCBVs for both VB-111 and combination groups demonstrated statistically significant association with OS (p=0.0198 and p=0.0458 respectively). In the VB-111 group, post-treatment srCBV also demonstrated significant association with OS (p=0.024). Whereas, in combination group, baseline MTT is significantly associated with OS (p=0.0323). Several cytokines 6h post VB-111 infusion correlated with overall survival including IL-1Rα, IL-17α, MIP1α, and TNFα (p<0.05). When U251 tumor microglia and T cells were cocultured with splenocytes and activated with LPS (72h), several cytokines including MIP1α, MIP1β, IL-10 and RANTES were significant higher from mice administered VB-111 (p<0.05). Conversely, using CD3/CD28 for activation, a decrease in immunosuppressive cytokines was observed including IL-10, 4, 3, and 5. These results suggested that tumoral microglia are responsible for cytokine release with a profile that promotes a cytotoxic T cell response. Improved survival in VB-111 treated patients correlates with both vascular imaging parameters and cytokine response, supporting both immune and anti-angiogenic mechanisms of this anti-cancer virotherapy.
P3.16-034 Impact of Travel Distance to Treatment Institution on Survival from Stage I to III Lung Cancer
Authors: C. Da Silva, G. Werutsky, A. Gelatti, M.T. Ruiz Tsukazan, G. Lenz, V. Sgnaolin, M. Rosa, R. D'Avila, P.R. Nunes Filho, P. Pacheco, J. Figueiredo Pinto, J. Rios, M.H. Sostruznik, F. Zaffaroni, A. Poisl Fay
Journal: Journal of Thoracic Oncology (2017)
P2.01-030 Real World Study of Bevacizumab-Contained Regimen as First Line Therapy in Chinese Patients with Advanced NSCLC
Authors: Y. Mu, P. Xing, Y. Wang, X. Hao, X. Hu, H. Wang, Y. Liu, Y. Wen, Y. Wang, J. Li
Journal: Journal of Thoracic Oncology (2017)
P1.04-003 The International Lung Screen Trial: A Multi-Center Study to Evaluate LDCT Screening Selection Criteria and Nodule Management
Authors: K.P. Lim, F. Brims, A. Mcwilliams, M. Tammemägi, C. Berg, H. Marshall, E. Stone, R. Manser, K. Canfell, L. Connelly, J. Yee, K. Fong, S. Lam
Journal: Journal of Thoracic Oncology (2017)
Rubéola na Dinamarca
Authors: S Glismann
Journal: Eurosurveillance (2004)

Ate 1987, foi registada anualmente uma media de 20 000 casos de rubeola na Dinamarca. Em 1989, contudo, foram apenas notificados 1006 casos, desconhecendo-se a verdadeira incidencia actual da infeccao da rubeola na Dinamarca, mas considera-se que seja muito baixa e l 1 por 100 000 individuos da populacao. A diminuicao significativa da incidencia da rubeola espelha o sucesso da vacinacao de mulheres seronegativas para a rubeola em idade reprodutora que foi iniciada na Dinamarca em 1980. A partir de 1982, o esquema de seguranca da saude nacional passou tambem a reembolsar a vacinacao de criancas, e a vacina MMR foi introduzida no programa de vacinacao da infância dinamarques em 1987. A baixa incidencia foi sustentavel gracas a estas intervencoes, e desde 1994 que o sindrome de rubeola congenita e a rubeola na gravidez estao listados como doencas infecciosas de notificacao na Dinamarca. Nao obstante, e visando cumprir o objectivo da OMS de controlo da rubeola na Regiao, esta agora em consideracao a introducao da nofiticacao notificacao obrigatoria de todos casos de rubeola diagnosticados laboratorialmente.
P2.06-001 A Study of MGCD516, a Receptor Tyrosine Kinase (RTK) Inhibitor, in Molecularly Selected Patients with NSCLC or Other Advanced Solid Tumors
Authors: Theresa Werner, Rebecca Heist, Richard Carvajal, Douglas Adkins, Ajjai Alva, Sanjay Goel, David Hong, Lyudmila Bazhenova, Mansoor Saleh, Robert Siegel, Christos Kyriakopoulos, Collin Blakely, Keith Eaton, Richard Lauer, Ding Wang, Gary Schwartz, Saskia Neuteboom, Diane Potvin, Demiana Faltaos, Isan Chen, James Christensen, Matteo Levisetti, Richard Chao, Todd Bauer
Journal: Journal of Thoracic Oncology (2017)
Carta a la redacción: Brotes de parvovirus B19
Authors: H Kelly, J Leydon
Journal: Eurosurveillance (2005)

In a recent issue of Eurosurveillance, Goncalves and colleagues reported that outbreaks of a rash illness in a kindergarten, a primary and a secondary school in the local health area of Braga in northern Portugal were due to human parvovirus B19 [1]. Although human parvovirus was suspected clinically, laboratory investigations were undertaken to exclude both measles and rubella as the cause of the outbreak, given that Portugal is approaching measles elimination. The authors noted that human parvovirus has been reported as a cause of rash illness, potentially as a differential diagnosis for measles and rubella, in developing and developed countries [1].
CMET-21. TOLERANCE AND OUTCOMES OF STEREOTACTIC RADIOSURGERY COMBINED WITH ANTI-PD1 (PEMBROLIZUMAB) FOR MELANOMA BRAIN METASTASES
Authors: Charlée Nardin, Christine Mateus, Matthieu Texier, Emilie Lanoy, Salima Hibat-Allah, Sami Ammari, Caroline Robert, Frederic Dhermain
Journal: Neuro-Oncology (2017)

Anti-PD1 antibodies are currently the first-line treatment for patients with metastatic BRAF wild- type melanoma, alone or combined with the anti-CTLA4 mAb, ipilimumab. To date, data on safety and the outcomes of patients treated with the anti-PD1 mAbs, pembrolizumab (PB) or nivolumab, combined with stereotactic radiosurgery (SRS) for melanoma brain metastases (MBM) are lacking. Patients with MBM treated with PB combined with SRS between 2012 and 2015 were retrospectively reviewed. The primary endpoint was neurotoxicity. The secondary endpoints were local control, distant intracranial control and overall survival (OS). Among 74 patients with MBM treated with SRS, 25 patients with a total of 58 MBM treated with PB combined with SRS within 6 months were included. Radionecrosis, occurring within a median time of 6.5 months, was observed in four metastases (6.8%) in four different patients. No significant other SRS-related adverse event had been reported. After a median follow-up of 8.4 months, local control had been achieved in 46 metastases (80%). The median time to local progression was 2 months. Perilesional oedema and intratumour haemorrhage appearing or increasing after SRS were mostly associated with local progression (P <0.001). Median OS was 15.3 months (95% CI 4.6–26). The timing between SRS and PB administration did not seem to influence radionecrosis, intracranial control or OS. SRS combined with PB was well tolerated and achieved satisfactory local control as described with nivolumab. There is a current study testing the association of anti-CTLA4 and anti-PD1 with radiotherapy for patients with melanoma metastases (excluding active MBM) that will provide data about the tolerance and the efficacy of this combination therapy. Prolonged OS were achieved compared to that currently yielded with recommended treatments. Prospective studies are required to confirm these results and define the best timing between SRS and anti-PD1 for the management of MBM.
GENE-33. THE 3D EVOLUTION AND IN VIVO GROWTH PATTERNS OF GLIOMA CELL POPULATIONS
Authors: Stephanie Hilz, Samuel J Shelton, Llewellyn Jalbert, Hang K Wong, Tali Mazor, Chibo Hong, Josie Hayes, Tracy Luks, Henrik Bengtsson, Annette Molinaro, Michael McDermott, Mitchel S Berger, Daniel Lim, Aaron Diaz, Joanna J Phillips, Susan Chang, Sarah Nelson, Michael C Oldham, Joseph Costello
Journal: Neuro-Oncology (2017)

Most cancers result from multiple clonal expansion events, resulting in tumors comprised of many subclones. The coexistence of these genetically distinct populations within a single tumor is thought to underlie the failure of most current treatments. Ascertaining how diverse populations of cells evolve within tumors, and the functional implications of this diversity, are the next steps to developing more informed treatments that overcome the barrier currently posed by intratumoral heterogeneity (ITH). Previous studies of adult diffuse glioma have been restricted in their ability to provide a detailed understanding of the spatial evolution of solid tumors due to insufficient sampling, typically just one biopsy per patient, and a lack of knowledge of where within the heterogeneous tumor the sample was obtained. We have developed a unique sample collection protocol, in which we record the precise, three-dimensional (3D) coordinate for each of 10 spatially-distinct samples obtained from each patient’s tumor. Whole exome data from IDH1 mutant grade II astrocytomas analyzed in this manner have revealed that expansion events are typically spatially segregated, suggesting minimal tumor-wide intermixing of subclonal cell populations in these low grade gliomas. Expression profiling of one particular case has furthermore revealed ITH of the immune microenvironment, uncovering a region of increased PD-L1 expression and IFN-gamma signaling. Ongoing analysis is focused on integrating genetic and expression profiles from these and additional spatially-mapped cases. This integrative analysis aims to dissect the relative contributions of subclonal variation and location within the tumor on gene expression patterns and ITH of the immune microenvironment. The delineation of the spatial patterns of ITH our work provides will enable more informed selection of biopsy targets in the future. It also lends greater insight into the factors shaping intratumoral variation of gene expression patterns and the immune microenvironment in adult diffuse glioma.
Gα12 overexpression induced by miR-16 dysregulation contributes to liver fibrosis by promoting autophagy in hepatic stellate cells
Authors: Kyu Min Kim, Chang Yeob Han, Ji Young Kim, Sam Seok Cho, Yun Seok Kim, Ja Hyun Koo, Jung Min Lee, Sung Chul Lim, Keon Wook Kang, Jae-Sung Kim, Se Jin Hwang, Sung Hwan Ki, Sang Geon Kim
Journal: Journal of Hepatology (2018)
ACTR-78. TAMIGA: A PHASE II STUDY EVALUATING THE EFFICACY AND SAFETY OF CONTINUOUS BEVACIZUMAB THROUGH MULTIPLE LINES OF TREATMENT FOR GLIOBLASTOMA
Authors: Alba Brandes, Miquel Gil Gil, Frank Saran, Antoine F Carpentier, Anna Nowak, Warren Mason, Francois Dubois, Gaetano Finocchiaro, George Fountzilas, Vittorina Zagonel, Dana M Cernea, Olivier Chinot, Martina Makrutzki, Chiedzo Mpofu, Hans-Joerg Urban, Josef Pichler
Journal: Neuro-Oncology (2017)

Bevacizumab (anti-vascular endothelial growth factor) prolongs progression-free survival (PFS) in newly diagnosed and recurrent glioblastoma. We hypothesized overall-survival (OS) benefit from continuing bevacizumab (BEV) through multiple lines of treatment (TML). Patients with newly diagnosed glioblastoma were enrolled in a multicenter, double-blind, placebo-controlled, randomized study (TAMIGA/NCT01860638). First-line (1L) treatment was radiotherapy plus temozolomide and BEV with maintenance treatment consisting of temozolomide plus BEV (six cycles) and BEV monotherapy until first disease progression (PD1). After PD1, patients were randomized to receive lomustine (CCNU) plus BEV or CCNU + placebo (P) until PD2. After PD2, patients received BEV plus chemotherapy (investigator choice; CIC) or P+CIC. Primary endpoint: OS. Secondary endpoints: PFS, OS rates, and safety. Overall, 296 patients were enrolled and 123 patients (due to withdrawal) were randomized at PD1 (BEV+CCNU, n=61; P+CCNU, n=62). After PD2, 25 patients in each arm received third-line treatment. Baseline characteristics were generally balanced. At randomization, 32.8% and 30.6% of the patients were receiving corticosteroids for BEV and placebo, respectively. The study terminated prematurely, due to the high withdrawal rate, implying underpowered (i.e. power=60%) inferential testing. For BEV versus placebo, respectively: median OS from randomization was 6.4 vs 5.5 months (HR=1.04, 95% CI 0.69–1.59); 6-month OS rate was 49.2% vs 38.7%; median time to corticosteroid initiation during second-line treatment was 5.8 vs 5.4 months; 86% and 83% had an adverse event (AE); 19% and 15% had ≥1 treatment-related grade ≥3 AEs; 21% and 15% had AEs leading to discontinuation. The study was underpowered for analysis of the primary endpoint. Descriptive analyses suggest neither an improvement nor detriment with the addition of BEV TML, in recurrent glioblastoma. No new safety signals were observed.
Eribulin mesylate in advanced breast cancer: retrospective review of a single institution experience
Authors: R. Di Cicilia, A. Garcia-Arias, A. Berselli, E. Gervasi, G. Stridi, C. Bonelli, A. Romagnani, R. Gnoni, A. Bologna, G. Moretti, A. Bologna, C. Pinto
Journal: Annals of Oncology (2017)
Interpretation of Urine Drug Screens
Authors: Geeta Nagpal, Heather Heiman, Shannon Haymond
Journal: JAMA (2017)

A comprehensive urine drug screen for a 50-year-old woman taking daily methadone, immediate-release morphine, gabapentin, duloxetine, and celecoxib for pain was positive for methadone and morphine but also codeine and hydromorphone. How do you interpret the results?
Activated Hedgehog-GLI Signaling Causes Congenital Ureteropelvic Junction Obstruction
Authors: Sepideh Sheybani-Deloui, Lijun Chi, Marian V. Staite, Jason E. Cain, Brian J. Nieman, R. Mark Henkelman, Brandon J. Wainwright, S. Steven Potter, Darius J. Bagli, Armando J. Lorenzo, Norman D. Rosenblum
Journal: Journal of the American Society of Nephrology (2017)

Export Intrinsic ureteropelvic junction obstruction is the most common cause of congenital hydronephrosis, yet the underlying pathogenesis is undefined. Hedgehog proteins control morphogenesis by promoting GLI-dependent transcriptional activation and inhibiting the formation of the GLI3 transcriptional repressor. Hedgehog regulates differentiation and proliferation of ureteric smooth muscle progenitor cells during murine kidney-ureter development. Histopathologic findings of smooth muscle cell hypertrophy and stroma-like cells, consistently observed in obstructing tissue at the time of surgical correction, suggest that Hedgehog signaling is abnormally regulated during the genesis of congenital intrinsic ureteropelvic junction obstruction. Here, we demonstrate that constitutively active Hedgehog signaling in murine intermediate mesoderm–derived renal progenitors results in hydronephrosis and failure to develop a patent pelvic-ureteric junction. Tissue obstructing the ureteropelvic junction was marked as early as E13.5 by an ectopic population of cells expressing Ptch2, a Hedgehog signaling target. Constitutive expression of GLI3 repressor in Ptch1-deficient mice rescued ectopic Ptch2 expression and obstructive hydronephrosis. Whole transcriptome analysis of isolated Ptch2+ cells revealed coexpression of genes characteristic of stromal progenitor cells. Genetic lineage tracing indicated that stromal cells blocking the ureteropelvic junction were derived from intermediate mesoderm–derived renal progenitors and were distinct from the smooth muscle or epithelial lineages. Analysis of obstructive ureteric tissue resected from children with congenital intrinsic ureteropelvic junction obstruction revealed a molecular signature similar to that observed in Ptch1-deficient mice. Together, these results demonstrate a Hedgehog-dependent mechanism underlying mammalian intrinsic ureteropelvic junction obstruction.
MA 12.03 Kinase Fusions as Recurrent Mechanisms of Acquired Resistance in EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC)
Authors: S. Ou, S. Klempner, B. Creelan, W.S. Hsieh, D. Costin, P.J. Stephens, J. Ross, V. Miller, S. Ali, A. Schrock
Journal: Journal of Thoracic Oncology (2017)
P1.05-011 Comparison of Tumor Measurement Methods in Patients with Clinical Stage IA Non-Small Cell Lung Cancer
Authors: T. Nagashima, H. Ito, J. Samejima, J. Osawa, K. Inafuku, M. Nito, H. Nakayama, K. Yamada, T. Yokose
Journal: Journal of Thoracic Oncology (2017)
MA 15.13 The Transfer of Exogenous UCHL-1 via Mesenchymal Lung Cancer Exosomes to Mediate Phenotypic Alterations of Recipients
Authors: Y. Shimada, P. Yenerall, K. Huffman, K. Avila, H. Park, B. Timmons, B. Gao, D. Deb, N. Ikeda, J. Minna
Journal: Journal of Thoracic Oncology (2017)