tbuckley/cabot-search huggingface dataset:
Abstract 15240: Cholesterol Crystal Embolization: The Incidence as a Cardiac Procedural Complication and the Comparison of the Outcomes Between its Causes
Authors: Ayumi Misao, Kazushige Kadota, Daiji Hasegawa, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Yasushi Fuku, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Circulation (2015)

Background: Cholesterol crystal embolization (CCE) is very rare, but has a poor prognosis and no proven therapy. Although CCE occurs from various causes, the incidence and outcomes of CCE remain unclear. Purpose: 1) to investigate the incidence of CCE as a complication of percutaneous coronary intervention (PCI), percutaneous transluminal angioplasty (PTA), and cardiovascular surgery; and 2) to investigate patient characteristics and outcomes of CCE on the basis of its causes: idiopathic CCE, catheter-related CCE, and cardiovascular surgery-related CCE. Methods: We registered 75 patients having CCE in the medical records between May 2004 and April 2014 and compared their patient characteristics and outcomes according to the causes of CCE: idiopathic CCE, 31 patients (41%); catheter-related CCE, 32 (43%); and cardiovascular surgery-related CCE, 12 (16%). CCE was diagnosed by clinical findings (blue toe syndrome or livedo) or laboratory findings (elevated serum creatinine level, eosinophil count, or skin biopsy). Results: The incidences of catheter-related CCE were 0.7% in PTA on arteriosclerotic obliterans and 0.17% in PCI. The incidence of CCE after PCI was significantly higher in patients treated with femoral approach than in those treated with nonfemoral approach (0.32% vs. 0.01%, p&lt;0.001). The incidences of cardiovascular surgery-related CCE were relatively high in endovascular aortic repair (1.3%) and in abdominal aortic replacement (0.6%). In the comparison of patient characteristics between idiopathic CCE, catheter-related CCE, and cardiovascular surgery-related CCE, there were significant differences in age and aortic aneurysm. Of the 75 patients, 24 (32%) died, 10 (13%) initiated dialysis, and 7 (9%) underwent leg or toe amputation. There was no significant difference in the outcomes of CCE depending on its causes. Conclusion: The incidences of CCE were significantly high in transfemoral procedures and in surgery for abdominal aortic aneurysm. Between the causes of CCE, there were significant differences in patient characteristics, but no significant differences in the outcomes.
RADI-18. DIFFUSION KURTOSIS IMAGING CAN HELP DIFFERENTIATE LOW- AND HIGH-GRADE GLIOMAS IN PEDIATRIC PATIENTS: A PROSPECTIVE SINGLE CENTRE STUDY
Authors: Ioan Paul Voicu, Antonio Napolitano, Chiara Carducci, Lorenzo Lattavo, Maria Camilla Rossi Espagnet, Andrea Carai, Antonella Cacchione, Mara Vinci, Angela Mastronuzzi, Paolo Tomà, Giovanna Stefania Colafati
Journal: Neuro-Oncology (2018)

To investigate whether diffusion kurtosis imaging (DKI) can be helpful in differentiating low- and high-grade gliomas (LGG and HGG respectively) in pediatric patients. MATERIALS AND After obtaining informed consent, thirty-two consecutive children (median age 8.5 years, 17 M) affected by histologically confirmed brain gliomas were prospectively studied on a 3T magnet with a 32-channel head coil. Conventional sequences and DKI sequences (30 directions, 3 b values: 0, 1000, 2000) acquired with the simultaneous multislice (SMS) technique were obtained. Mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK) and fractional anisotropy (FA) values were calculated and the corresponding maps were obtained. The enhancing and nonenhancing tumor volumes (VOIs) were segmented semiautomatically. Mean and highest 20 percentile (H20%) DKI values in tumor VOIs were calculated for each metric. Differences among DKI values in the enhancing and nonenhancing VOIs of low and high-grade gliomas (LGG and HGG respectively) were assessed with an independent sample t test. After excluding three patients for motion artifacts, the scans of twenty-nine children (20 LGG and 9 HGG) were analyzed. Significantly different mean RK, H20% RK and mean MK values were found in the enhancing tumor VOI between LGG and HGG (p<0.029, p<0.015 and p<0.05 respectively). DKI can be helpful in differentiating low and high-grade gliomas in pediatric patients.
IMMU-09. OUTCOME OF PATIENTS WITH RECURRENT DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) TREATED WITH PEMBROLIZUMAB (ANTI-PD-1): A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY (PBTC045)
Authors: Eugene Hwang, Arzu Onar, Tina Young-Poussaint, Duane Mitchell, Lindsay Kilburn, Ashley Margol, Stephen Gilheeny, Tong Lin, Ira Dunkel, Maryam Fouladi
Journal: Neuro-Oncology (2018)

Children with diffuse intrinsic pontine glioma (DIPG) have a dismal prognosis. Checkpoint blockade has revolutionized treatment of some resistant cancers. Pembrolizumab, a PD-1 inhibitor, was administered to children with progressive DIPG (Stratum A) and results are reported here. Children aged 1-18yrs with progressive DIPG were eligible with functional scores >60 and physiologic or less steroid usage, among standard eligibility criteria. Pembrolizumab was administered at 2mg/kg IV every three weeks. Tumor tissue (if available), serum and MRI studies were collected for correlative analysis. Five patients with progressive DIPG were enrolled from June-July 2015. The median age at diagnosis was 3.5yrs (range,2.8-6.9), and median time from diagnosis to study entry was 14.6 months (range,8.7-20.7). Progression-free survival (PFS) was 1.02 months (range,0.5-1.7); overall survival from initial treatment was 1.7 months (range,0.5-6.2). All patients clinically and/or radiographically worsened after one (n=1) or two (n=4) doses of pembrolizumab. Grade 3 or greater treatment-related adverse events included fatigue (n=2) and new or increased grade neurologic symptoms. Correlative analysis is ongoing. Checkpoint inhibition holds potential for CNS cancer treatment; however, special consideration is required in the CNS with limited space and large disease burdens. In our study, patients rapidly deteriorated neurologically after initiation of checkpoint blockade, with a shorter median PFS than expected by analogous historical trials; pembrolizumab protocols were amended to exclude recurrent DIPG patients after these events. Our findings suggest caution when utilizing immunotherapy in actively progressing tumor in the brain stem.
Clinical and histopathologic features of paraneoplastic granuloma annulare in association with solid organ malignancies: A case–control study
Authors: Aaron R. Mangold, Helen J.L. Cumsky, Collin M. Costello, Daniel Y. Xie, Matthew R. Buras, Steven A. Nelson, David J. DiCaudo, Aleksandar Sekulic, Mark R. Pittelkow
Journal: Journal of the American Academy of Dermatology (2018)
ATRT-16. CONGENITAL RHABDOID TUMORS AS A MAJOR CLINICAL CHALLENGE - A COLLABORATIVE EUROPEAN EFFORT
Authors: Karolina Nemes, Nathalie Clément, Denis Kachanov, Susanne Bens, Tatyana Shamanskaya, Svetlana Varfolomeeva, Kornelius Kerl, Floor Abbink, Martin Ebinger, Stephan Tippelt, Norbert Graf, Martin Hasselblatt, Pablo Hernáiz-Driever, Maria João Gil-Da-Costa, Thomas Klingebiel, Rolf-Dieter Kortmann, Jane Pears, Paul-Gerhardt Schlegel, Nicolas Andre, Anne-Isabelle Bertozzi, Nadège Corradini, Christelle Dufour, Fanny Fouyssac, Pierre Leblond, Olivier Delattre, Julien Masliah-Planchon, Thorsten Simon, Beate Timmermann, Olaf Witt, Reinhard Schneppenheim, Joachim Gerss, Reiner Siebert, Rhoikos Furtwängler, Franck Bourdeaut, Christoph Frühwald
Journal: Neuro-Oncology (2018)
CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer
Authors: Yelena Y. Janjigian, Johanna Bendell, Emiliano Calvo, Joseph W. Kim, Paolo A. Ascierto, Padmanee Sharma, Patrick A. Ott, Katriina Peltola, Dirk Jaeger, Jeffry Evans, Filippo de Braud, Ian Chau, Christopher T. Harbison, Cecile Dorange, Marina Tschaika, Dung T. Le
Journal: Journal of Clinical Oncology (2018)

Metastatic esophagogastric cancer treatments after failure of second-line chemotherapy are limited. Nivolumab demonstrated superior overall survival (OS) versus placebo in Asian patients with advanced gastric or gastroesophageal junction cancers. We assessed the safety and efficacy of nivolumab and nivolumab plus ipilimumab in Western patients with chemotherapy-refractory esophagogastric cancers.
GERM-08. EARLIER RECOGNITION OF SYMPTOMS AND DIAGNOSIS MAY REDUCE TREATMENT AND LATE EFFECT BURDEN IN CHILDREN, TEENAGERS AND YOUNG ADULTS WITH INTRACRANIAL GERM CELL TUMOURS
Authors: James Hayden, Ute Bartels, Anthony Penn, Matthew Murray, Gabriele Calaminus, James Nicholson
Journal: Neuro-Oncology (2018)

Prolonged symptom intervals (SI) are frequently seen in malignant intracranial germ cell tumours (iGCTs) and have been associated with inferior outcomes in other brain tumours. This study reviewed the clinical presentation of iGCTs and examined the effect of prolonged SI on this group. Clinical data were retrospectively reviewed for patients (diagnosed with an iGCT (January 2002-December 2011) from 6 centres [4 UK (n=45), 1 German (n=11) and 1 Canadian (n=31)]. Fisher’s exact test used for comparisons (p<0.05 significant). Study cohort included 87 (58M:29F) patients [59 germinoma, and 28 non-germinoma] with tumours located in pineal (34), suprasellar (25), bifocal (24) and other area (4), of which 16 were metastatic. Median age at diagnosis was 11.5 years (0.6-22.6y). The time to diagnosis from first symptom (SI) ranged from 0-69 months (median 3m, mean 8.5m). A prolonged SI (> 6months) was observed in one third of patients (n=28) and significantly associated with metastatic disease (11/28 vs. 5/59, p=0.002) at diagnosis. In patients with a prolonged SI, endocrine symptoms, particularly diabetes insipidus (DI), were common (75%) but raised intracranial pressure (RICP) was infrequent (14%). In contrast, those with a SI <6 months frequently presented with RICP (84%, p<0.0001). One third of patients with an iGCT have symptoms >6 months prior to diagnosis. Delayed diagnosis is associated with metastatic disease. Early symptom recognition, particularly related to hormonal disturbances without RICP, may improve timely diagnosis, reduce frequency of metastatic disease and thus reduce the burden of treatment and late-effects.
Itaconic acid mediates crosstalk between macrophage metabolism and peritoneal tumors
Authors: Jonathan M. Weiss, Luke C. Davies, Megan Karwan, Lilia Ileva, Michelle K. Ozaki, Robert Y.S. Cheng, Lisa A. Ridnour, Christina M. Annunziata, David A. Wink, Daniel W. McVicar
Journal: Journal of Clinical Investigation (2018)

Control of cellular metabolism is critical for efficient cell function, although little is known about the interplay between cell subset–specific metabolites in situ, especially in the tumor setting. Here, we determined how a macrophage-specific (Mϕ-specific) metabolite, itaconic acid, can regulate tumor progression in the peritoneum. We show that peritoneal tumors (B16 melanoma or ID8 ovarian carcinoma) elicited a fatty acid oxidation–mediated increase in oxidative phosphorylation (OXPHOS) and glycolysis in peritoneal tissue–resident macrophages (pResMϕ). Unbiased metabolomics identified itaconic acid, the product of immune-responsive gene 1–mediated (Irg1-mediated) catabolism of mitochondrial cis-aconitate, among the most highly upregulated metabolites in pResMϕ of tumor-bearing mice. Administration of lentivirally encoded Irg1 shRNA significantly reduced peritoneal tumors. This resulted in reductions in OXPHOS and OXPHOS-driven production of ROS in pResMϕ and ROS-mediated MAPK activation in tumor cells. Our findings demonstrate that tumors profoundly alter pResMϕ metabolism, leading to the production of itaconic acid, which potentiates tumor growth. Monocytes isolated from ovarian carcinoma patients' ascites fluid expressed significantly elevated levels of IRG1. Therefore, IRG1 in pResMϕ represents a potential therapeutic target for peritoneal tumors.
ATRT-32. PREPARATION OF GENETIC TESTING SYSTEM OF AT/RT FOR PEDIATRIC CANCER PREDISPOSITION PROGRAM
Authors: Chikako Kiyotani, Ryota Shirai, Yui Kimura, Yoko Sioda, Tomoo Osumi, Motohiro Kato, Daisuke Tomizawa, Kenichi Usami, Hideki Ogiwara, Hidekazu Aoki, Yoshiyuki Tsutsumi, Hiroshi Fuji, Rie Irie, Takako Yoshioka, Kimikazu Matsumoto, Keita Terashima
Journal: Neuro-Oncology (2018)

Atypical teratoid rhabdoid tumors (AT/RTs) are highly aggressive embryonal CNS tumors. Up to one-third of AT/RTs are reported to have germline mutation and/or deletion of SMARCB1/hSNF5. In accordance with the increased understanding for pediatric cancer predisposition syndrome, the needs for genetic counseling and testing is expanding. And next generation suquencing technique is inevitable for these genotyping. So we start to prepare genetic testing system of AT/RT for future pediatric cancer predisposition program. Proior to the genetic testing, pretest counseling is performed for each patient/family. Informed consent was obtained according to the institutional ethical review board. Genomic DNA was isolated from the patient's periphera blood, and somatic DNA was extracted from frozen tissues or FFPE samples. Genetic analysis of the SMARCB1 coding sequence was performed by Sanger method. Deletion of SMARCB1 is examined by quantitative analysis of each exon with droplet digital PCR (ddPCR). SNP array analysis is also tried if frozen sample is available. Three AT/RT patients and one rhabdoid tumor patient received genetic testing. None of them had germline mutation. In an infant ATRT, Sanger sequence analysis revealed frameshift mutation (c649-650delAT). Also, ddPCR showed uniparenteral heterodisomy (UPD). In another AT/RTs, copy number decrease and UPD over whole region of SMARCB1, or exon 3 deletion are recognized respectively. Rhabdoid tumor case had nonsense mutation (c610C>T). Although most of AT/RT should have biallelic mutation, false negative could happen due to less tumor cells obtained in those samples. Enlightenment for sampling and accumulation for testing would be important.
ATRT-22. SWI/SNF COMPLEX HETEROGENEITY RELATES WITH POLYPHENOTYPIC DIFFERENTIATION AND THE IMMUNE MICRO ENVIRONMENT IN RHABDOID TUMORS
Authors: Sriram Venneti, Pooja Panwalkar, Chan Chung, Drew Pratt, Daniel Martinez, Jill Bayliss, Christopher Paran, Debra Hawes, Bruce Pawel, Alexander Judkins
Journal: Neuro-Oncology (2018)

Malignant rhabdoid tumors (MRT), including central nervous system (CNS) Atypical Teratoid / Rhabdoid Tumors (AT/RT) and extra CNS (eCNS) MRT, are aggressive cancers characterized by loss of SMARCB1, a core component of the SWI/SNF chromatin-remodeling complex. Histopathologically, MRTs are characterized by polyphenotypic differentiation that varies from tumor to tumor. Because the SWI/SNF complex regulates differentiation we hypothesized that the SWI/SNF complex would exhibit heterogeneity in MRTs. We first characterized the SWI/SNF complex in developing human brain. SMARCB1 expression was highest in the cerebellum compared to hemispheric regions and remained so throughout development. In contrast, many subunits of the SWI/SNF complex were down regulated after cerebellar development. In MRTs we discovered that the SWI/SNF complex subunits showed marked differences between AT/RTs and eCNS MRTs. In eCNS MRTs high ACTL6A and ACTL6B expression was associated with neuronal differentiation while tumors with low ACTL6A and ACTL6B showed epithelial and mesenchymal differentiation. In AT/RTs there was marked heterogeneity in members of the PBAF complex including ARID2, BRD7 and PBRM1. Tumors with high PBAF expression were associated with worse prognosis, increased metastasis and cell cycle deregulation. Of the PBAF components, tumors with low PBRM1 showed a better prognosis and were associated with increased cytotoxic lymphocytes in their microenvironment. Our data demonstrate that MRTs exhibit heterogeneity in the SWI/SNF complex that may contribute to the polyphenotypic differentiation characteristic of these tumors, and which may have implications in understanding the biology, prognosis and development of immunotherapeutic approaches to these tumors.
CRAN-30. HIGH PRECISION STEREOTACTIC CONFORMAL RADIOTHERAPY (SCRT) IMPROVES THE LONG TERM FUNCTIONAL OUTCOME IN CHILDREN AND ADOLESCENT PATIENTS OF CRANIOPHARYNGIOMA: DATA FROM A PROSPECTIVE RANDOMIZED TRIAL
Authors: Jayant Goda, Uday Krishna, Debnarayan Dutta, Sadhna Kannan, Savita Goswami, Nazia Bano, Tejpal Gupta, Nalini Shah, Rajiv Sarin, Rakesh Jalali
Journal: Neuro-Oncology (2018)

To compare the clinical and functional outcome in young patients with craniopharyngioma treated with Stereotactic Conformal focal radiotherapy (SCRT) and conventional RT(ConvRT). Patients were assigned to either SCRT or ConvRT to a dose of 54 Gy in 30 fractions over 6 weeks. 82 patients (SCRT:39 & ConvRT 43; median age-11years [IQR: 8–17]) diagnosed with craniopharyngioma underwent serial longitudinal neurocognitive domains which included Full Scale Intelligence Quotient(FSIQ), Performance Quotient(PQ), Verbal Quotient(VQ), Memory Quotient(MQ) and neuroendocrine evaluation at baseline and follow-up after RT. Mild hydrocephalus was observed in 80% patients. NPS (0–1) was seen in 64% patients. Vision was impaired in 7%. Pre-RT mean VQ/MQ, PQ and FSIQ were 85.15, 83.90 and 79.38 and improved to 96.73(p=0.07), 101.79(0.002) and 87.71(p=0.06) respectively at 5 years post RT. Improvement in all the neurocognitive domains were better with SCRT technique as opposed to ConvRT technique over a period of 5 years [FSIQ(difference in slopes:-0.67), PQ(difference of slope:-1.22), VQ/MQ(difference of slope:0.57)]. At a median follow-up of 5.4 years (IQR 3.8 -7.2),80(97.5%)patients were locally controlled. 10-year overall survival and local control with SCRT was 74.1% & 97% compared to 80.6% & 95.2% with ConvRT. Cumulative incidence of developing any neuroendocrine dysfunction was lower in SCRT arm (12/39 patients, 30.7%) compared to ConvRT arm (20/43 patients, 45.6%). In young patients of craniopharyngioma requiring radiotherapy for long-term tumour control, SCRT as compared to ConvRT achieves superior neurocognitive and neuroendocrine functional outcomes over 5 years without compromising local control or survival.
DIPG-25. A KINOME-WIDE shRNA SCREEN UNCOVERS VRK3 AS AN ESSENTIAL GENE FOR DIPG SURVIVAL
Authors: Cláudia CS Evangelista, Emilie Barret, Jane Merlevede, Ambre Saccasyn, Stéphanie Puget, Jacques Grill, David Castel, Marie-Anne Debily
Journal: Neuro-Oncology (2018)

Diffuse Intrinsic Pontine Glioma (DIPG) remains the most fatal form of pediatric brain tumor. The specific somatic mutation (H3K27M) in the H3 histone gene was found in around 95% of patients making this alteration as the initial oncogenic event. However, until now this alteration cannot be targeted. Consequently, we conducted a RNAi-based loss-of-function screen targeting the human kinome to decipher vulnerabilities in DIPG, unravel their biology and provide therapeutic opportunities in this devastating disease. An integrative lentiviral pooled library of 7450 shRNAs against 770 kinases was used to transduce four GSC (glioma stem cells) cultures harboring either H3.1 (n=2) or H3.3-mutation (n=2) in order to cover the diversity observed in patients, and 2 control NSC (neural stem cell) cultures. The entire set of shRNAs was identified by sequencing 40 hours and 22 days after transduction. Genes required for cell expansion over 22 days of outgrowth in GSC but with limited deleterious effect on NSC proliferation were identified. Among those, we selected the target genes with at least 3 distinct shRNAs presenting a significant decrease in their abundance and identified in particular VRK3 (Vaccinia-Related Kinase 3) as one of the top scoring kinases whose extinction was lethal to DIPG. This serine-threonine kinase was recently linked to cell cycle progression, DNA repair and neuronal differentiation. The role of this protein in DIPG biology is currently assessed especially to identify actionable downstream targets. Drugs mimicking the effect of VRK3 extinction will be evaluated in our vitro and vivo models of DIPG.
Molecular profiling of gastrointestinal cancer
Authors: P. Apostolou, M. Papadimitriou, P. Parsonidis, A. Iliopoulos, I. Papasotiriou
Journal: Annals of Oncology (2018)

Introduction: Gastro-intestinal cancer (GI) include a variety of cancers that affect esophagus, gallbladder, liver, pancreas, stomach, intestine and other organs involved in digestive system. The above types of cancers appear higher mortality rates in comparison with cancers in other systems. Therefore, it is essential the optimization of treatment management. Even though great achievements have been performed the last years in prediction of cancer therapy, treatment is based in specific markers, avoiding genes that affect or affected through signaling transduction pathways. The present study aimed to analyze the gene expression in cancer cells, representing different GI cancer types and compare them with circulating tumor cells (CTCs) from patients and cells from normal donors. Methods: RNA was extracted from commercial cell lines representing gastric (MKN45, 23132/37), liver (Huh 7D-12), colon (CaCO2, HCT15, HCT116) and pancreatic (PANC-1) cancer. Blood was collected from two healthy donors as well as two colon cancer patients. PBMCs in healthy individuals and CTCs in cancer samples were isolated and RNA was extracted. qRT-PCR was performed including reference RNA as positive control. 80 primer pairs were designed for exon-exon amplification of genes involved in signaling pathways, invasion, receptors, cell cycle regulation, resistance etc. ACTB was used as housekeeping genes and DeltaCt analysis was followed. Experiments were performed in triplicates including appropriate controls. Hierarchical clustering was performed to identify gene expression patterns. Results: The genes ERK1, ERK2, CDC6, JAK1, JAK2, FAS, NRAS, BCL2, NME1 and HSPB1 were not expressed in normal samples, while different expression patterns were observed in commercial cancer cells and cells derived from patients. Regarding the migration-invasion marker NME1, and genes ERK1, BAX, RRM1, ERCC1, ARAF, MET, E2F1, ERBB2, MTOR, TYMS, GART, PNP, RRBP1 and HSPB1, commercial cells had higher expression. On the contrary, patients-derived cells' gene expression was higher for ERK2, PTEN, RPSA, JAK1, JAK2, FAS, KRAS, TGFB1 and NANOG. For the rest genes that were studied, there was not observed clear molecular profile. The clustering among samples revealed that cancer cells' gene expression pattern is different than normal, while dissimilar pattern was also observed between commercial cancer cells and CTCs. Conclusion: Taking everything into consideration it is well understood that personalized treatment is essential, since different expression profiles are observed among samples with the same type of cancer. The more genes that are studied, the more information are collected for the cancer; therefore a treatment with greater success can be achieved. In addition, the study of genes should not limited in receptors and/or pathways, but also to include genes involved in various cell processes. Further studies, in more samples, are imperative to confirm all the above and be able to use at clinical level.