tbuckley/cabot-search huggingface dataset:
LGG-36. DESMOPLASTIC INFANTILE GANGLIOGLIOMA (DIG) WITH A PPP1CB-ALK FUSION IN A 6-YEAR-OLD GIRL
Authors: William McDonald, Mahmoud Nagib, Robert Jenkins, Cristiane Ida, Kevin Halling, Mary Skrypek, Anne Bendel
Journal: Neuro-Oncology (2020)

Abstract Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are benign glioneuronal tumors that typically occur in infants, involve the superficial cerebral cortex, and have an excellent prognosis. DIA/DIG are a distinct molecular entity based on DNA methylation profiling. BRAF600 mutations are frequently reported in DIG/DIA. A recent comprehensive genetic analysis of infantile hemispheric gliomas identified 2 unique groups: group 1 harbored alterations in the receptor tyrosine kinase (RTK) genes ALK, ROS1, NTRK, and MET and group 2 harbored alterations in the RAS/MAPK pathway. We report a case of a 6.5-year-old girl who presented with seizures and right homonymous hemianopia. MRI of her brain demonstrated a large cystic/solid left hemispheric mass with remodelling of the overlying skull, consistent with a long-standing process. She underwent a gross total resection (GTR) and pathology demonstrated a DIG with a PPP1CB-ALK gene fusion (exon 5 to exon 20) identified by RNA sequencing. She remains disease free 12 months following GTR. A literature review identified 4 reported cases of pediatric brain tumors with PPP1CB-ALK gene fusions including: a 3-month-old with a hemispheric high-grade glioma which recurred 4 years later and pathology showed mature ganglioglioma, with both tumors showing the identical PPP1CB-ALK gene fusion; a 10-month-old infant with a hemispheric low-grade glioma; an infant with a “congenital” hemispheric high-grade glioma; and a child with an astrocytoma with no further clinical data. PPP1CB-ALK gene fusion appears to be a rare oncogenic driver in gliomas of infancy, including DIG.
Hepatic Artery Aneurysm
Authors: R B Lal, J A Strohl, S Piazza, M Aslam, D Ball, K Patel
Journal: JAMA (1963)

A 67-year-old man presented with epigastric pain and underwent cholecystectomy for acute acalculus cholecystitis. Exploration revealed a large aneurysm in the hepatic artery. One week later, the patient developed jaundice, ascending cholangitis and common bile duct obstruction. He was treated with percutaneous transhepatic drainage with dramatic improvement, then underwent an emergency aneurysm resection operation. He is now well, 8 months postoperatively. Due to the high mortality rate associated with hepatic artery aneurysm, treatment is primarily surgical with aneurysmorrhaphy or direct arterial reconstruction utilizing either autogenous saphenous vein or prosthetic grafts. For inaccessible aneurysms or when patients are unfit to withstand surgery, embolization is a useful alternative.
PATH-11. PROSPECTIVE (EPI-)GENETIC CLASSIFICATION OF &amp;gt; 1,000 PEDIATRIC CNS TUMORS—THE MNP 2.0 STUDY
Authors: Dominik Sturm, Felix Sahm, Felipe Andreiuolo, David Capper, Marco Gessi, Agata Rode, Brigitte Bison, Steffen Hirsch, Nicolas U Gerber, Nicholas G Gottardo, Christof M Kramm, Stefan Rutkowski, Andreas von Deimling, Torsten Pietsch, Stefan M Pfister, David T W Jones
Journal: Neuro-Oncology (2020)

Abstract The large variety of CNS tumor entities affecting children and adolescents, some of which are exceedingly rare, results in very diverging patient outcomes and renders accurate diagnosis challenging. To assess the diagnostic utility of routine DNA methylation-based CNS tumor classification and gene panel sequencing, the Molecular Neuropathology 2.0 study prospectively integrated these (epi-)genetic analyses with reference neuropathological diagnostics as an international trial for newly-diagnosed pediatric patients. In a four-year period, 1,215 patients with sufficient tissue were enrolled from 65 centers, receiving a reference neuropathological diagnosis according to the WHO classification in &amp;gt;97%. Using 10 FFPE sections as input, DNA methylation analysis was successfully performed in 95% of cases, of which 78% with sufficient tumor cell content were assigned to a distinct epigenetic tumor class. The remaining 22% did not match any of 82 represented classes, indicating novel rare tumor entities. Targeted gene panel sequencing of &amp;gt;130 genes performed for 96% of patients with matched blood samples detected diagnostically, prognostically, or therapeutically relevant somatic alterations in 48%. Germline DNA sequencing data indicated potential predisposition syndromes in ~10% of patients. Discrepant results by neuropathological and epigenetic classification (29%) were enriched in histological high-grade gliomas and implicated clinical relevance in 5% of all cases. Clinical follow-up suggests improved survival for some patients with high-grade glioma histology and lower-grade molecular profiles. Routine (epi-)genetic profiling at the time of primary diagnosis adds a valuable layer of information to neuropathological diagnostics and will improve clinical management of CNS tumors.
TBIO-27. RASOPATHIES AND BRAIN TUMOROGENESIS: ARE SOS1 MUTATIONS ARE CONCERNED?
Authors: Nouha Bouayed Abdelmoula, Rim Louati, Balkiss Abdelmoula, Samir Aloulou
Journal: Neuro-Oncology (2020)

Abstract Germ line gain-of-function mutations in several members of the RAS/MAPK pathway, including PTPN11 are associated with signalopathies named Rasopathies and known as Noonan syndrome and closely related conditions. Patients harboring Rasopathies are at increased risk of myeloproliferative diseases and solid tumors, such as neuroblastoma. Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, represent the second most frequent genetic defect in Rasopathies. However, SOS1 mutations are rare in human malignancies and patients with germline SOS1 mutations may not be at increased risk of developing cancer. Here, we report a SOS1 variant found to segregate in a Tunisian pedigree with many members affected by brain tumors as well as epileptic disorder. During our genetic counselling for congenital heart diseases, a 9-year-old female born at Sfax from a consanguineous couple and having pulmonic valvular stenosis, has been investigated at the molecular level. Screening of mutations in the entire coding sequence of PTPN11, Braf and SOS1, was conducted using HRM analysis and bidirectional sequencing. Heterozygous single nucleotide substitution of SOS1 gene: c.1655 G&amp;gt;A was confirmed. This mutation affected the PH-REM linker domain with substitution of residue Arg552 to Lys: p.Arg552Lys. This mutation accounts for one-third of all mutations reported in SOS1 during Rasopathies. Although no other molecular exploration was done, family history revealed other affected children by neurodevelopmental and epileptic conditions as well as recurrent brain malignancies in the paternal family. Two aunts developed blindness and then died subsequently to tumor progression.
Reducing Adolescent Psychopathology in Socioeconomically Disadvantaged Children With a Preschool Intervention: A Randomized Controlled Trial
Authors: Karen L. Bierman, Brenda S. Heinrichs, Janet A. Welsh, Robert L. Nix
Journal: American Journal of Psychiatry (2020)

Objective: Living in poverty increases exposure to adversities that undermine healthy development, impeding growth in the social-emotional and language skills that support adaptive coping and promote mental health. Evidence-based programs have the potential to improve current preschool practice and strengthen these early skills, potentially reducing risk for later psychopathology. The authors tested the hypothesis that an enrichment program in preschool would be associated with reduced levels of psychopathology symptoms at the transition from middle to secondary school. Methods: The Head Start REDI (Research-Based, Developmentally Informed) intervention was used to enrich preschool classrooms serving children from low-income families with an evidence-based social-emotional learning (SEL) program and a coordinated interactive reading program. Centers were randomly assigned to the intervention or usual practice, and 356 4-year-olds (58% White, 25% Black, 17% Latino; 54% female) were followed into early adolescence. Hierarchical linear models were used to evaluate intervention effects on teacher-rated psychopathology symptoms using the Strengths and Difficulties Questionnaire in grade 7 (ages 12–13) and grade 9 (ages 14–15), 8–10 years after the end of the intervention. Results: Statistically significant intervention-related reductions were observed in conduct problems and emotional symptoms in the intervention group. In addition, the proportion of youths with clinically significant levels of conduct problems, emotional symptoms, and peer problems was reduced in the intervention group, with rates one-third of those in the control group. Conclusions: The study findings indicate that enriching preschool programs serving at-risk children with a relatively inexpensive evidence-based SEL program with interactive reading substantially improved the later benefits for adolescent emotional and behavioral health. This kind of SEL enrichment represents an approach that can leverage public investments in preschool programs to enhance public health.
Viable virus aerosol propagation by positive airway pressure circuit leak and mitigation with a ventilated patient hood
Authors: Shane A. Landry, Jeremy J. Barr, Martin I. MacDonald, Dinesh Subedi, Darren Mansfield, Garun S. Hamilton, Bradley A. Edwards, Simon A. Joosten
Journal: European Respiratory Journal (2020)

Introduction Nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major feature of the COVID-19 pandemic. Evidence suggests patients can auto-emit aerosols containing viable viruses; these aerosols could be further propagated when patients undergo certain treatments, including continuous positive airway pressure (PAP) therapy. Our aim was to assess 1) the degree of viable virus propagated from PAP circuit mask leak and 2) the efficacy of a ventilated plastic canopy to mitigate virus propagation. Methods Bacteriophage phiX174 (10 8 copies·mL −1 ) was nebulised into a custom PAP circuit. Mask leak was systematically varied at the mask interface. Plates containing Escherichia coli host quantified viable virus ( via plaque forming unit) settling on surfaces around the room. The efficacy of a low-cost ventilated headboard created from a tarpaulin hood and a high-efficiency particulate air (HEPA) filter was tested. Results Mask leak was associated with virus contamination in a dose-dependent manner (χ 2 =58.24, df=4, p&lt;0.001). Moderate mask leak (≥21 L·min −1 ) was associated with virus counts equivalent to using PAP with a vented mask. The highest frequency of viruses was detected on surfaces &lt;1 m away; however, viable viruses were recorded up to 3.86 m from the source. A plastic hood with HEPA filtration significantly reduced viable viruses on all plates. HEPA exchange rates ≥170 m 3 ·h −1 eradicated all evidence of virus contamination. Conclusions Mask leak from PAP may be a major source of environmental contamination and nosocomial spread of infectious respiratory diseases. Subclinical mask leak levels should be treated as an infectious risk. Low-cost patient hoods with HEPA filtration are an effective countermeasure.
DIPG-54. A NON-INVASIVE PROGNOSTIC CIRCULATING miRNAs SIGNATURE IN DIFFUSE INTRINSIC PONTINE GLIOMAS
Authors: Maria Federica Iannò, Elisabetta Schiavello, Andrea Carenzo, Andrea Anichini, Veronica Biassoni, Lorenza Gandola, Loris De Cecco, Maura Massimino
Journal: Neuro-Oncology (2020)

Abstract Diffuse intrinsic pontine gliomas (DIPG) are the most common brainstem tumors of childhood and represent one of the most challenging paediatric tumours to treat. A non-randomized, open label phase II pilot study was conducted at Fondazione IRCCS Istituto Nazionale Tumori (Milan) to assess the efficacy in terms of objective response rate according to the RECIST criteria of combining nimotuzumab and vinorelbine with radiation in newly-diagnosed DIPG. Serum specimens were collected at baseline. microRNA expression profiling was performed using Agilent platform and Human miRNA SureSelect 8x60K containing 2006 miRNAs annotated on miRBase19.0. Primary data analysis yielded a matrix containing 330 detectable miRNA. Association with PFS allowed us to disclose a signature of 10 miRNAs able to stratify high and low risk patients (HR=4.33, 95%CI 1.49–12.54; p=4.27E-05). To test the 10 ct-miRNA model performance, we collected an independent cohort of the same sample size (n=24) and we derived the index values and risk stratification. The distribution of index values covers a range similar to the discovery cohort. Imposing the signature threshold patients were divided in high/low risk and Kaplan-Meier curves confirmed the different PFS time for the two groups with HR=3.5 (95%CI: 1.8–8.01, p-value=0.0002) for the high-risk patients, reaching AUC=0.833. Our signature is a biomarker based on non-invasive procedures for prognosis able to enter into clinical practice. Further validation on multicenter case series is warranted.
The Impact of Cytogenetic Clonality on Outcomes in Younger Acute Myeloid Leukemia Patients: Results on 1290 Patients Included in the EORTC/Gimema AML-10 and AML-12 Trials
Authors: Frederic Baron, Marian Stevens-Kroef, Michal Kicinski, Giovanna Meloni, Petra Muus, Jean-Pierre Marie, Constantijn J.M. Halkes, Xavier Thomas, Radovan Vrhovac, Crescenza Pasciolla, Francois Lefrere, Simona Sica, Marco Mancini, Adriano Venditti, Anne Hagemeijer, Heiko Becker, Joop H. Jansen, Sergio Amadori, T. M. M de Witte, Roelof Willemze, Stefan Suciu
Journal: Blood (2017)
EPCO-10. CHANGES IN ALTERNATIVE SPLICING AND ASSOCIATED NEOANTIGENS DUE TO THERAPY
Authors: Lin Wang, Karin Shamardani, Husam Babikir, Francisca Catalan, Takahide Nejo, Susan Chang, Joanna Philips, Hideho Okada, Aaron Diaz
Journal: Neuro-Oncology (2020)

Abstract Recent studies have identified alternative splicing (AS) as a novel source of neoantigens for immunotherapy. Surprisingly little is known about the AS milieu in recurrent glioblastoma (GBM), despite this being the venue for most clinical trials. We profiled 29 primary-recurrent paired human GBM specimens via RNA sequencing and re-analyzed RNA-sequencing data from non-malignant human brain tissues. From these data, we reconstructed the landscape of AS in GBM through recurrence and contrasted that to isoforms observed in non-malignant brain. The AS events we identified were cross-referenced with single-cell GBM atlases to determine cell-type specific splicing patterns. From this we identified novel splicing events in cell-surface proteins that are suitable targets for engineered T-cell therapies. We found recurrent-specific isoforms of mitogen-activated kinase pathway genes which are expressed exclusively by GBM stem-like cells that enhance invasiveness. These studies shed light on the effect of therapy on AS and identify novel targets for emerging immunotherapies.
RADT-05. CLINICAL OUTCOMES OF PROTON CRANIOSPINAL IRRADIATION FOR PATIENTS WITH LEPTOMENINGEAL CARCINOMATOSIS
Authors: N Ari Wijetunga, Nader Mohammed, Yoshiya Yamada, Suzanne Wolden, Andrew Seidman, Helena Yu, Mark Kris, Rachna Malani, Elena Pentsova, Adrienne Boire, T Jonathan Yang
Journal: Neuro-Oncology (2020)

Abstract Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic tumors. Radiotherapy (RT) is integral to LC treatment, and proton craniospinal irradiation (CSI) may make RT more effective by targeting the entire central nervous system (CNS) compartment. We evaluated outcomes in patients treated with proton CSI for LC. We identified 56 patients treated with proton CSI for LC between 2018 and 2020 at our institution. Data on patient demographics, disease and treatment history, cerebrospinal fluid circulating tumor cells (CSF CTCs), and gene alterations were collected. Kaplan Meier analysis and Cox regression models were used to compare correlates with CNS time to progression (TTP), CNS progression-free survival (PFS) and overall survival (OS). Most patients had non-small cell lung cancer (NSCLC, n=27, 48%) or breast cancer (n=21, 38%). The median age was 58 (30-77), and median KPS was 80 (60-90). The median RT dose was 30Gy (25-36). The median follow-up was 12 months (1-22), with 26 (46%) patients alive at the last follow-up. Of 35 (63%) patients who progressed, 6 (11%) progressed in the CNS, 13 (23%) progressed systemically, and 16 (29%) progressed in both. The median TTP, PFS and OS was 8 months (1-21), 6 months (1-21) and 8 months (1-22), respectively. No difference in PFS (7 vs. 6 months, p=0.6) and OS (8 vs. 7 months, p=0.3) was observed between patients with NSCLC and breast cancer. Of patients alive at 3 months, 79% showed stable or improved functional status after CSI. Decreased CSF CTCs immediately post CSI had significantly improved PFS (8 vs. 5 months with no CTC decrease, HR=0.3, p=0.02). Lastly, we identified genetic correlates with survival outcomes. Proton CSI appears to be a promising treatment for LC in select patients, resulting in prolonged CNS disease control and survival. A randomized trial is currently underway to assess its efficacy prospectively.
American College of Surgeons Efforts in Support of Value-Based Metrics—Reply
Authors: Jill R. Dietz, Peter Pronovost
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
PATH-05. A CASE OF PILOCYTIC ASTROCYTOMA HARBORING THE FGFR1 GENE MUTATION WITH A PREDOMINANT OLIGODENDROGLIOMA-LIKE COMPONENT
Authors: Nobuyoshi Sasaki, Tomohiro Chiba, Kuniaki Saito, Keiichi Kobayashi, Yoshiaki Shiokawa, Junji Shibahara, Motoo Nagane
Journal: Neuro-Oncology (2020)

Abstract Pilocytic astrocytomas rarely present with oligodendroglioma-like morphological features, which gives rise to a diagnostic challenge. In this report we present a case of pilocytic astrocytoma harboring the FGFR1 mutation, accompanied with a predominant oligodendroglioma-like component, thus initially diagnosed as oligodendroglioma. A 14-year-old female presented with syncope and simple partial seizure involving her right upper limb. Contrast-enhanced MRI revealed an enhancing lesion with substantial cystic portion and perifocal edema in the left parietal lobe. Open surgery was performed and a gross total resection of the tumor was achieved. On initial histopathological diagnosis, tumor cells with monotonous round nuclei and perinuclear halo predominated with branching capillaries, which were strongly suggestive for oligodendroglioma. Immunohistochemically, IDH1 R132H was negative, and Ki-67 index was around 5%. The patient was thus initially diagnosed as oligodendroglioma, WHO grade II, based on the 2007 WHO classification criteria. However, histopathological re-review revealed a minor astrocytic component with Rosenthal fibers and rare eosinophilic granular bodies, thus the diagnosis was changed as pilocytic astrocytoma. FGFR1 K654E mutation was confirmed by Sanger sequencing. Although she postoperatively developed mild sensory disturbance in her right hands, finger agnosia, and left-right disorientation, her symptoms had gradually improved, and she was discharged on day 17 with a Karnofsky performance status (KPS) of 90 and no cognitive decline. Without any adjuvant therapies, she has remained recurrence-free for 85 months. While the diagnosis of pilocytic astrocytoma with predominant oligodendroglioma-like component can be challenging, analysis of IDH1 and FGFR1 mutations can be beneficial in certain cases.
TAMI-35. AUTOPHAGY MEDIATED LIPID CATABOLISM FACILITATES GLIOMA PROGRESSION TO OVERCOME BIOENERGETIC CRISIS
Authors: Chenran Wang, Michael Haas, Syn Yeo, Ritama Paul, Fuchun Yang, Subrahmanya Vallabhapurapu, Xiaoyang Qi, David R Plas, Jun-Lin Guan
Journal: Neuro-Oncology (2020)

Abstract Activation of mTORC1 plays a significant role in cancer development and progression. However, the metabolic mechanisms to sustain mTORC1 activation in stressed cancer cells are still underappreciated. Autophagy, one downstream process of mTORC1, is proposed to be suppressed under the condition of mTORC1 hyper-activation. Interestingly, we recently revealed higher autophagy activity in various Tsc-deficient tumor cells with mTORC1 hyper-activity. Nevertheless, the functions and mechanisms of autophagy in regulating mTORC1 in cancer cells are not well understood. In this study, we revealed a strong association of altered mRNA levels in mTORC1 upstream and downstream genes with poor prognosis of glioma patients. Our metabolic and molecular studies indicated that autophagy mediated lipid catabolism was essential to sustain mTORC1 activity in glioma cells under energy stresses. We found that autophagy inhibitors or fatty acid oxidation (FAO) inhibition in combination with 2-Deoxy-D-glucose (2DG) decreased oxidative phosphorylation, ATP production, mTORC1 activity, and survival of glioma cells in vitro. Consistently, the combination of chloroquine (CQ) or FAO inhibitors with 2DG effectively suppressed the progression of xenografted glioma with mTORC1 hyperactivation in mice. This study established a novel autophagy/lipid degradation/FAO/ATP pathway that maintains high mTORC1 signaling and tumor progression in brain cancer cells under energy stresses. The requirement of lipophagy in brain cancers may provide an opportunity to develop new molecular therapeutic targets to counteract mTORC1 for tumor progression.