tbuckley/cabot-search huggingface dataset:
SURG-14. ENDOSCOPIC SURGERY FOR PEDIATRIC INTRAVENTRICULAR TUMOR WITHOUT HYDROCEPHALUS: INDICATION, SURGICAL TECHNIQUE, AVOIDANCE OF COMPLICATION, AND ITS PROSPECT
Authors: Shunsaku Takayanagi, Hirokazu Takami, Shota Tanaka, Masahiro Shin, Nobuhito Saito
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Neuroendoscopic surgery is useful for intraventricular tumors accompanied by ventriculomegaly. However, it is often challenging for cases with small ventricles. Our institution is actively performing surgeries for pediatric intraventricular tumors without frank ventriculomegaly. METHODS Seven cases of intraventricular tumors without ventriculomegaly (5 cases of subependymal giant cell astrocytoma (SEGA) and 2 cases of germ cell tumors (GCTs)) were analyzed. The age ranged between 3 and 14 years (median 5 years). The sizes of SEGA were between 10-27mm, and all the tumors showed an enlargement around the foramen of Monro, which was the indication for surgery. Biopsy and third ventriculostomy were performed for GCTs. For resection, after making a small craniotomy of 2 x 3 cm, ellipse-cone-like sheath with a diameter of 12mm or 17mm was inserted through it to the lateral ventricle, which enabled a wide surgical view. Under a rigid endoscope of 4mm diameter, 2 types of surgical instruments were employed, making the microsurgical procedure like under a microscope, with a wider view, possible. For the cases of tumor resection, septostomy and placement of a drain in the ventricle were performed at the end of surgery. RESULTS The lesions were safely approached in all the cases. For resection, endoscopic microsurgery was possible, and tumor was totally removed in all the cases. No postoperative complication was observed in any of them. CONCLUSIONS Our experience shows that tumor resection can be safely achieved with the aid of endoscope even for cases without ventriculomegaly.
Annular Plaques in a Woman Receiving Systemic Immunotherapy
Authors: Jessica Wu, Mengjun Hu, Suzanne M. Sachsman
Journal: JAMA Dermatology (2020)

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EPCO-17. A SINGLE-CELL ATLAS OF GLIOBLASTOMA EVOLUTION UNDER THERAPY
Authors: Lin Wang, Husam Babikir, Karin Shamardani, Francisca Catalan, Sweta Sudhir, Gary Kohanbash, Manish Aghi, Susan Chang, Joanna Philips, Aaron Diaz
Journal: Neuro-Oncology (2020)

Abstract Most clinical trials for glioblastoma (GBM) enroll patients at recurrence. However, most pre-clinical animal models are of primary disease. Most studies have used tissues from primary tumors. Knowledge of GBM cellular composition at recurrence is limited. We profiled 80 human IDH-wild-type GBM specimens via single-nucleus RNA sequencing, 40 primary tumors and 40 patient-matched recurrent tumors. Select cohorts were also profiled via single-cell assay for transposase-accessible chromatin, single-cell digital-spatial, and single-cell spatial-transcriptomic assays. All patients were treated only with standard-of-care therapy: temozolomide, radiation and surgical resection. The cohort had a 1.2 male/female ratio, ages 35–76. We found a significant increase at recurrence in cells with the Verhaak mesenchymal phenotype and fewer proneural cells. Although there was an increase in the percentage of cycling cells overall, the fraction of cycling proneural cells decreased while the fraction of cycling mesenchymal cells increased. These changes were concomitant with a significant increase in the percentage of tumor-infiltrating monocytic-lineage cells derived from the periphery. Taken together, these findings support a proneural-to-mesenchymal shift at recurrence due to an increase in the birth rate of mesenchymal cells, supported by an expansion of myeloid-derived cells from peripheral blood. Although the percentages of glioblastoma-infiltrating T-cells are generally low (~1% on average in our data), we found a statistically significant increase in T-cell abundance at recurrence. We identified a cohort of T-cell outliers that demonstrate 2-to-8-fold increases in T-cells over average levels. We validated that T-cells in these tumors have extravasated beyond the perivascular space and into the cellular tumor via immunohistochemistry and single-cell spatial profiling. We present our ongoing analysis of the paracrine signals, upstream transcription-factor expression, and cis-regulatory grammars utilized in immune-outlier GBMs. We describe how these programs change under therapy. These studies shed light on the effect of standard therapy in shaping GBM composition at recurrence.
QOLP-07. HEALTH-RELATED QUALITY OF LIFE AND SYMPTOM BURDEN IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA TREATED WITH BEVACIZUMAB BEYOND PROGRESSION: A PROSPECTIVE TRIAL
Authors: Shota Tanaka, Yoshitaka Narita, Akitake Mukasa, Motoo Nagane, Tomokazu Aoki, Toshihiko Wakabayashi, Takeo Uzuka, Hideo Nakamura, Yoshiki Arakawa, Satoshi Suehiro, Mitsutoshi Nakada, Satoshi Morita, Mamoru Kato, Kouichi Ichimura, Ryo Nishikawa
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND In BIOMARK trial, patients with newly diagnosed glioblastoma were treated with standard chemoradiotherapy combined with first-line bevacizumab; a subset of patients continued bevacizumab beyond progression (BBP). Neurocognitive function (NCF), symptom burden, and health-related quality of life (HRQoL) were examined as secondary endpoints. PATIENTS AND METHODS In the primary protocol, newly diagnosed glioblastoma patients aged 20-75 received standard 6-week radiotherapy combined with temozolomide and bevacizumab followed by 4-week cycles of temozolomide plus bevacizumab, and then 2-3-week cycles of bevacizumab monotherapy. Upon recurrence, patients were subjected to the secondary protocol with 2-3-week cycles of bevacizumab monotherapy with or without other chemotherapeutic agents. NCF tests (Hopkins verbal learning test-revised, trail making test, and controlled oral word association), EORTC QLQ-C30/BN20, and MDASI-BT were completed by the patients. Time to deterioration (TTD) was defined as the time from randomization until a pre-specified change from baseline without further improvement or death. The Kaplan-Meier method and the log-rank test were used to assess TTD for each subscale of the above tests. RESULTS Overall, 94 patients were enrolled in the study. Analyses were based on the full analysis set cohort (N=90), excluding non-glioblastoma diagnosis by central review. The median overall survival (OS) and progression-free survival (PFS) were 25.0 and 14.9 months, respectively. Baseline HRQoL and symptom burden subscales (emotional functioning, symptom severity score, affective factor, and focal factor) were significantly associated with PFS. The median TTD was 8.7, 7.5, 8.1 months for global health status/QoL, symptom severity score, interference score, respectively. Among patients who experienced recurrence, disease progression was apparently preceded by deterioration in terms of symptom burden. CONCLUSIONS Detailed analysis of HRQoL and symptom burden may aid care of glioblastoma patients throughout the disease trajectory.
SeSaMe: Metagenome Sequence Classification of Arbuscular Mycorrhizal Fungi-Associated Microorganisms
Authors: Jee Eun Kang, Antonio Ciampi, Mohamed Hijri
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract Arbuscular mycorrhizal fungi (AMF) are plant root symbionts that play key roles in plant growth and soil fertility. They are obligate biotrophic fungi that form coenocytic multinucleated hyphae and spores. Numerous studies have shown that diverse microorganisms live on the surface of and inside their mycelia, resulting in a metagenome when whole-genome sequencing (WGS) data are obtained from sequencing AMF cultivated in vivo. The metagenome contains not only the AMF sequences, but also those from associated microorganisms. In this study, we introduce a novel bioinformatics program, Spore-associated Symbiotic Microbes (SeSaMe), designed for taxonomic classification of short sequences obtained by next-generation DNA sequencing. A genus-specific usage bias database was created based on amino acid usage and codon usage of a three consecutive codon DNA 9-mer encoding an amino acid trimer in a protein secondary structure. The program distinguishes between coding sequence (CDS) and non-CDS, and classifies a query sequence into a genus group out of 54 genera used as reference. The mean percentages of correct predictions of the CDS and the non-CDS test sets at the genus level were 71% and 50% for bacteria, 68% and 73% for fungi (excluding AMF), and 49% and 72% for AMF (Rhizophagus irregularis), respectively. SeSaMe provides not only a means for estimating taxonomic diversity and abundance but also the gene reservoir of the reference taxonomic groups associated with AMF. Therefore, it enables users to study the symbiotic roles of associated microorganisms. It can also be applicable to other microorganisms as well as soil metagenomes. SeSaMe is freely available at www.fungalsesame.org.
EXTH-70. CYP450 AND METABOLIC PROFILING OF ANTI-CANCER IMIPRIDONE ONC201
Authors: Sara Morrow, Varun Prabhu, Rohinton S Tarapore, Ailan Guo, Yunlan Fang, Magdalena Nej, Martin Stogniew, Joshua Allen
Journal: Neuro-Oncology (2020)

Abstract Imipridone ONC201 is an investigational agent in phase II clinical trials for high grade gliomas as a single agent once weekly. Systemic and tumor exposure to ONC201 exceeds therapeutic thresholds consistently; however, exposure is variable despite fasted conditions and does not strongly covary with body weight or body surface area. Clinical trials with ONC201 have restricted the use of concomitant medication that induce or inhibit cytochrome P450 (CYP) enzymes; however, several supportive medications for glioma patients such as corticosteroids and anti-seizure medications can affect these enzymes. Studies in pooled human liver microsomes revealed that ONC201 is not an inducer of seven major drug-metabolizing human CYP enzymes: CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4. However, ONC201 inhibits multiple CYPs IC50 values ranging from 34.9 to 428.6 μM and is substrate of CYP3A4 and, to lesser extent, other CYPs. Given potential metabolism of ONC201 by these enzymes, we conducted metabolic profiling in human hepatocytes that revealed at least 13 metabolites; however, only one was &amp;gt;10% abundance. The major metabolite, termed ONC207, that lacks a benzyl moiety of ONC201 was assayed by LC-MS-MS in plasma samples obtained from 16 ONC201-treated H3 K27M-mutant glioma patients. Peak plasma concentrations of ONC207 relative to ONC201 was 22% (range: 6%-48%) and its abundance was not correlated with ONC201, suggesting that variable exposure to ONC201 may not be associated with variable metabolism. ONC207 does not inhibit dopamine receptor D2 or cancer cell viability in contrast to the parent compound. In summary, ONC201 is an inhibitor and substrate, but not an inducer, of multiple CYP enzymes. The major metabolite of ONC207 appears to be biologically inactive and is unlikely to explain variable ONC201 exposure or its prolonged biological activity that outlives its systemic presence.
PATH-08. THE IMPORTANCE OF RE-DIAGNOSIS OF TUMORS PREVIOUSLY CLASSIFIED AS CENTRAL NERVOUS SYSTEM PRIMITIVE NEUROECTODERMAL TUMORS
Authors: Naohide Fujita, Osamu Akiyama, Akihide Kondo
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The recent molecular analyses have revealed that central nervous system primitive neuroectodermal tumors (CNS PNETs) those having clusters of small round tumor cells are genetically different tumors. However, the concepts of CNS PNET are complicated, and it is difficult to diagnose them appropriately in clinical field. To overcome this difficulty, we reviewed previous studies associated with CNS PNETs, and carried out several approaches, those are relatively easy access to use in clinics, for our 8 samples of embryonal brain tumors diagnosed CNS PNETs in our institution, initially. METHODS We used in combination with immunohistochemistry (IHC), Sanger sequence, Pyrosequence, polymerase chain reaction (PCR), real time PCR and copy number analysis referring recent reports. RESULTS In terms of the diagnosis three out of 8 cases were changed based on the results in this study from previous diagnoses. CONCLUSION In this review, it seemed that either the histopathological evaluation or molecular analyses would be not enough to make accurate diagnosis of CNS embryonal brain tumors, and it is essential to combine both of them including recent comprehensive analysis methods.
PATH-24. DETECTION OF POINT MUTATIONS AND GENE FUSIONS FROM CIRCULATING CELL-FREE DNA (CFDNA) OF GLIOBLASTOMA (GBM) PATIENTS
Authors: Milana Frenkel-Morgenstern, Vikrant Palande, Rajesh Detroja, Alessandro Gorohovski, Rainer Glass, Charlotte Flueh, Andrew A Kanner, Yoseph Laviv, Sagi Har Nof, Adva Levy-Barda, Alexandra Benouaich-Amiel, Shlomit Yust-Katz, Marina Kurtz, Shira Perez, Dorith Raviv Shay, Tali Siegal
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND GBM is characterized by intratumoral heterogeneity. Tumor heterogeneity, clonal diversity and mutation acquisition hamper the ability to tailor personalized therapy for GBM. Tumor sampling has limited ability to accurately capture the molecular landscape of the tumor and to disclose acquired molecular aberrations. Mutation analysis of cfDNA is a non-invasive procedure which may overcome these limitations as it may reflect the real composition of the tumor and track the molecular evolution. We sequenced cfDNA of GBM patients and assessed mutation patterns and fusion genes. METHODS We collected blood and respective tumor samples from 27 GBM patients and blood samples from 14 healthy controls. Tumor DNA, cfDNA and WBC DNA were sequenced using deep sequencing procedures. The data were analyzed for detection of single nucleotide polymorphism (SNPs) and gene-gene fusions. RESULTS GBM cfDNA concentrations were significantly elevated (median: 23.63 ng/mL; range 12.6–137) compared to healthy controls (median 2.06; range 1.68–7.62) (p &amp;lt; 0.0001). We identified unique SNPs in each glioma patient’s cfDNA and the corresponding tumor DNA including the top-10 most frequently mutated genes in GBM. For example, mutation of TP53 was detected in18.75%; EGFR in 37.5%; NF1-12.5%; LRP1B-25% and IRS4 in 25%. For gene-gene fusion we used the in-house fusion gene database, ChiTaRS 5.0, and identified fusions in cfDNA and tumor DNA. Thus, KMT2A-FLNA was the most frequent fusion found in 16.4% of samples. BCR-ABL1 in 8.82% and FGFR1-BCR in 2.94%. Other fusions included COL1A1-PDGFB (5.88%), NIN-PDGFRB (5.88%), KIF5B-RET (5.88%) and also TPM3-ROS1(2.94%), TFG-ALK(2.94%), MSN-ALK (2.94%) and NPM1-ALK (2.94%) which may be targeted by brain penetrating drugs that are ROS1 and ALK inhibitors. CONCLUSIONS Our study suggests that plasma cfDNA analysis may help to uncover real time mutational and gene fusion status of GBM by a non-invasive procedure. It may identify drug targets based on personalized gene-gene fusions.
Drug-Eluting Stenting for Unprotected Left Main Coronary Artery Disease: Are We Ready to Replace Bypass Surgery?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Donald S. Baim, Laura Mauri, Donald C. Cutlip
Journal: Journal of the American College of Cardiology (2006)
NIMG-46. RADIOGENOMIC FEATURES PREDICT CLINICALLY RELEVANT GENOME-WIDE ALTERATION SIGNATURES IN GLIOBLASTOMA
Authors: Nicholas Nuechterlein, Beibin Li, James Fink, David Haynor, Eric Holland, Linda Shapiro, Patrick Cimino
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Previously, we have shown that combined whole-exome sequencing (WES) and genome-wide somatic copy number alteration (SCNA) information can separate IDH1/2-wildtype glioblastoma into two prognostic molecular subtypes (Group 1 and Group 2) and that these subtypes cannot be distinguished by epigenetic or clinical features. However, the potential for radiographic features to discriminate between these molecular subtypes has not been established. METHODS Radiogenomic features (n=35,400) were extracted from 46 multiparametric, pre-operative magnetic resonance imaging (MRI) of IDH1/2-wildtype glioblastoma patients from The Cancer Imaging Archive, all of whom have corresponding WES and SCNA data in The Cancer Genome Atlas. We developed a novel feature selection method that leverages the structure of extracted radiogenomic MRI features to mitigate the dimensionality challenge posed by the disparity between the number of features and patients in our cohort. Seven traditional machine learning classifiers were trained to distinguish Group 1 versus Group 2 using our feature selection method. Our feature selection was compared to lasso feature selection, recursive feature elimination, and variance thresholding. RESULTS We are able to classify Group 1 versus Group 2 glioblastomas with a cross-validated area under the curve (AUC) score of 0.82 using ridge logistic regression and our proposed feature selection method, which reduces the size of our feature set from 35,400 to 288. An interrogation of the selected features suggests that features describing contours in the T2 abnormality region on the FLAIR MRI modality may best distinguish these two groups from one another. CONCLUSIONS We successfully trained a machine learning model that allows for relevant targeted feature extraction from standard MRI to accurately predict molecularly-defined risk-stratifying IDH1/2-wildtype glioblastoma patient groups. This algorithm may be applied to future prospective studies to assess the utility of MRI as a surrogate for costly prognostic genomic studies.
LGG-16. PILOMYXOID ASTROCYTOMA OF THE CERVICAL SPINAL CORD IN A 7-YEAR-OLD ARMENIAN BOY: A CASE REPORT
Authors: Anna Avagyan, Lilit Sargsyan, Julia Hoveyan, Samvel Iskanyan, Samvel Bardakhchyan, Samvel Danielyan, Gevorg Tamamyan
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Pilomyxoid astrocytoma (PMA) is a glial tumor that occurs predominantly in the hypothalamic-chiasmatic region and rarely in spinal cord. It has similar features as pilocytic astrocytomas, with some distinct histological characteristics and worse prognosis. The 2007 WHO recognized PMA as a Grade II glioma due to its aggressive behavior and dissemination tendency, but according to 2016 version grading of the pilomyxoid variant is under research. Here we report a case with a rare location, aggressive behavior and rapid progression. CASE PRESENTATION: A 7-year-old boy presented with headache, nausea, vomiting. Imaging revealed an intramedullary tumor extending from C2 to C6 with hydrocephalus. A ventriculo-peritoneal shunt and complete surgical resection were performed with significant improvement in the patient’s condition. Histopathological findings were consistent with pilomyxoid variant of pilocytic astrocytoma, with negative BRAF V600E and MGMT. Three months later, the follow-up imaging revealed disease recurrence with leptomeningeal metastases, for which the patient received standard-dose craniospinal irradiation 35.2 Gy with boosts to tumor bed and metastatic sites 49.6 Gy and 54 Gy respectively. 11 months later tumor progression was revealed with new metastatic lesions in the bones. Patient received 6 cycles of chemotherapy with TMZ and Avastin, but continued to suffer disease progression on therapy and he succumbed to his disease at 24 months from diagnosis. CONCLUSION Given the rarity of documented patients with spinal pilomyxoid astrocytoma with rapid progression, as well as the lack of certain WHO classification and treatment guidelines, this case report might be useful for development of more efficient treatment strategies.
Impact of Cancer in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Alexander Lind, Matthias Totzeck, Amir A. Mahabadi, Rolf A. Jánosi, Mohamed El Gabry, Arjang Ruhparwar, Simone M. Mrotzek, Lena Hinrichs, Merve Akdeniz, Tienush Rassaf, Raluca I. Mincu
Journal: JACC CardioOncology (2020)

The use of transcatheter aortic valve replacement (TAVR) in cancer survivors and patients with active cancer (AC) in cancer survivors and patients with active cancer (AC) is expanding, suggesting a need to adjust the indications and risk assessment pre-TAVR.The purpose of this study was to determine the impact of cancer on peri-procedural complications and survival in a long-term, single-center cohort of patients treated with TAVR.Patients treated with TAVR between January 2006 and December 2018 were grouped as follows: controls (patients without cancer), stable cancer (SC), and AC. The primary endpoints were peri-procedural complications and 30-day survival. A secondary endpoint was 10-year survival.A total of 1,088 patients (age 81 ± 5 years, 46.6% men) treated with transfemoral TAVR were selected: 839 controls, 196 SC, and 53 AC. Predominant malignancies were breast, gastrointestinal, and prostate cancer. No differences were observed between patients with cancer and controls regarding peri-procedural complications. Patients with AC had similar 30-day survival compared with controls and SC (94.3% vs. 93.3% vs. 96.9%, p = 0.161), but as expected, reduced 10-year survival. AC was associated with a 1.47 (95% CI 1.16 to 1.87) fold increased risk of all-cause 10-year mortality in multivariable adjusted models.TAVR should be performed in patients with cancer when indicated, considering that patients with cancer have similar periprocedural complications and short-term survival compared with control patients. However, patients with AC have worse 10-year survival. Future studies are needed to define cancer-specific determinants of worse long-term survival.