tbuckley/cabot-search huggingface dataset:
SURG-15. A NOVEL RISK MODEL TO DEFINE THE RELATIVE BENEFIT OF MAXIMAL EXTENT OF RESECTION WITHIN PROGNOSTIC GROUPS IN NEWLY DIAGNOSED DIFFUSE LOW-GRADE GLIOMA
Authors: Shawn Hervey-Jumper, Annette Molinaro, Joanna Phillips, Ramin Morshed, Jacob Young, Yalan Zhang, Marisa LaFontaine, Tracy Luks, Simon Ammanuel, Sofia Kakaizada, Javier Villanueva-Meyer, Anny Shai, Gayathri Warrier, Terri Rice, Yi Lin, Jason Crane, Margaret Wrensch, John Wiencke, Nancy Ann Oberheim Bush, Jennie Taylor, Nicholas Butowski, Jennifer Clarke, Susan Chang, Edward Chang, Manish Aghi, Philip Theodosopoulos, Mitchel Berger
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The overall prognostic significance of maximal surgical resection in patients with diffuse low-grade glioma has been well established. Nonetheless, prior studies omit the combined importance of molecular subclass, patient characteristics, and chemoradiation. Similar to findings recently published in newly diagnosed glioblastoma, incorporation of these interactive factors may redefine the relative benefit of cytoreductive surgery. METHODS We examine the interactive effects of volumetric extent of resection with molecular and clinical factors to develop a new roadmap for cytoreductive surgery. Based on a 20-year retrospective cohort of 556 patients with WHO II diffuse low-grade glioma treated with surgery at UCSF 444 had complete records for survival modeling and recursive partitioning (RPA) to investigate multivariate relationships of overall and progression free survival. RESULTS Regardless of molecular subtype, patients with tumor volume under 55cm3 and postoperative volume of residual under 1.9cm3 experience the longest OS (median OS: not reached). Patients with volume of residual over 1.9cm3 experience a OS similar to that of patients with large (over 55cm3) oligodendrogliomas (median OS: not reached). Patients faring worst have large (over 55cm3) astrocytic gliomas (median OS: 84.8 months). Patients not treated with chemotherapy and either ATRX wild-type tumors or ATRX-mutant tumors with small (under 1cm3) volume of residual have the longest PFS together with chemotherapy treated patients who receive either no radiation or radiation for p53-mutant tumors under 30cm3 (median PFS 119 months). Patients with the shortest PFS are under 32-years with larger volume of residual (&amp;gt;1cm3), who receive no chemotherapy for ATRX-mutant tumors together with patients who receive both chemoradiation for larger (&amp;gt;30cm3) p53 mutant tumors (median PFS 30.8 months). CONCLUSION This is the first study to combine extent of resection with molecular and clinical information which paves the way for rethinking surgical strategies for individual patients with newly diagnosed low-grade gliomas.
Effect of Routine Cytochrome P450 2D6 and 2C19 Genotyping on Antipsychotic Drug Persistence in Patients With Schizophrenia
Authors: Gesche Jürgens, Stig E. Andersen, Henrik B. Rasmussen, Thomas Werge, Heidi D. Jensen, Benjamin Skov Kaas-Hansen, Merete Nordentoft
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Genetic polymorphism of genes encoding the drug metabolizing enzymes, cytochrome P450 2D6 and 2C19 (<i>CYP2D6</i>and<i>CYP2C19</i>), is associated with treatment failure of and adverse reactions to psychotropic drugs. The clinical utility of routine<i>CYP2D6</i>and<i>CYP2C19</i>genotyping (CYP testing) is unclear. <h3>Objective</h3> To estimate whether routine CYP testing effects the persistence of antipsychotic drug treatment. <h3>Design, Setting, and Participants</h3> This single-masked, 3-group randomized clinical trial included patients aged 18 years or older who had been diagnosed within the schizophrenic spectrum (<i>International Statistical Classification of Diseases and Related Health Problems, Tenth Revision </i>codes, F20-F29) and not previously genotyped. A total of 669 of 1406 potentially eligible patients from 12 psychiatric outpatient clinics in Denmark were approached between July 2008 and December 2009. Overall, 528 patients were genotyped and randomly allocated to 1 of 3 study groups or exclusion in a sequence of 1:1:1:3 using a predictive enrichment design, aiming to double the proportion of poor or ultrarapid metabolizers for CYP2D6 or CYP2C19. Outcome measurements were recorded at baseline and 1-year follow-up. Data analysis was performed in December 2012 and updated March 2019. <h3>Interventions</h3> The trial included 2 intervention groups, where antipsychotic drug treatment was guided by either CYP test (CYP test–guided [CTG]) or structured clinical monitoring (SCM), in which adverse effects and factors influencing compliance were systematically recorded at least once quarterly, and 1 control group. <h3>Main Outcomes and Measures</h3> Primary outcome was antipsychotic drug persistence, ie, days to first modification of the initial treatment. Secondary outcomes were number of drug and dose changes, adverse effects, and psychotic symptoms, ie, hallucinations and delusions. <h3>Results</h3> A total of 528 participants were genotyped, and 311 (median [interquartile range {IQR} age, 41 [30-50] years; 139 [45%] women; median [IQR] duration of illness, 6 [3-13] years) were randomly allocated to 1 of 3 study groups. Overall, 61 participants (20%) were extreme metabolizers. There was no difference in antipsychotic drug persistence between the CTG group and the control group (hazard ratio [HR], 1.02; 95% CI, 0.71-1.45) or SCM and the control group (HR, 0.88; 95% CI, 0.61-1.26). Subanalyses among extreme metabolizers showed similar results (CTG: HR, 0.99; 95% CI, 0.48-2.03; SCM: HR, 0.93; 95% CI, 0.44-1.96). <h3>Conclusions and Relevance</h3> The results of this randomized clinical trial do not support routine CYP testing in patients with schizophrenia. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT00707382
COVD-27. THE COVID-19 PANDEMIC AND NEURO-ONCOLOGICAL PATIENTS
Authors: Sofya Norman, Rupa Juthani
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION The Coronavirus disease 2019 (COVID-19) pandemic has uprooted healthcare systems worldwide, disrupting care and increasing dependence on alternative forms of health care delivery. It is yet to be determined how the pandemic affected neuro-oncology patient outcomes, given that the majority of even “elective” neurosurgical oncology procedures are time-sensitive. This study quantifies changes in neuro-oncological care during the height of the pandemic in New York City and investigates patient outcomes in 2020 compared to a historical control. METHODS We performed a retrospective review of patients with brain tumor diagnoses (primary or secondary) who were seen at the Weill Cornell Brain and Spine Center between March 13, 2020 and May 1, 2020. A control cohort from the corresponding time period in 2019 was also reviewed. Alterations in care, including shift from in-person to telehealth, delays in evaluation and intervention, and treatment modifications were evaluated. These variables were analyzed with respect to brain tumor control and mortality. RESULTS 114 patients from 2020 and 171 patients from 2019 were included, with no significant difference in baseline demographics between the groups. There was no significant difference in outcomes between the cohorts, despite significantly more treatment delays (p= 0.0154) and use of telehealth (p&amp;lt; 0.0001) in 2020. For patients treated during the pandemic in 2020, patients who experienced delays in care did not suffer from worse outcomes compared to those without delays. Patients who utilized telehealth visits had significantly more stable tumor control (P = 0.0027), consistent with appropriate use of in-person visits for patients with progression. CONCLUSION Our study showed that use of telehealth and selective alterations in neuro-oncological care during the COVID-19 pandemic did not lead to adverse patient outcomes. This suggests that adaptive physician-led changes during the pandemic were successful and effective. Further studies are needed to evaluate impact on long-term survival.
EPID-01. METASTATIC BRAIN TUMORS IN THE CENTRAL TEXAS MILITARY AND VETERAN POPULATION
Authors: Jennifer Murillo, Jared Benge, Danijela Levacic, Elizabeth Anyanda
Journal: Neuro-Oncology (2020)

Abstract There are relatively few studies on brain metastases in the military population, despite increased risk factors for the development of some cancers. This data was compared to the results from previously published epidemiological data Surveillance, Epidemiology, and End Results (SEER; Cagney et al, 2017) from the general population. PURPOSE: The purpose of our research was to compare the frequency and etiology of metastatic brain cancer in the military and veteran population in our database relative to the general population. METHODS: Retrospective chart review of diagnoses retrieved from the Electronic Medical Record dated January 1, 2016 to July 1, 2019 capturing visits to the Baylor Scott &amp; White Medical Center with specific ICD 10 brain cancer codes for nonhematologic malignancies originating outside of the CNS. RESULTS: Data from 63 individuals that met criteria for the study was analyzed. The military group was predominantly male (92.1%), white (66.7%) and non-Hispanic (90.5%). In our current sample (N=63) 74.6% had metastatic lung cancer with a histology subset of 24.5% having adenocarcinoma. Compared to the SEER general population our sample was more likely to have metastatic lung cancer with a similar frequency in the histologic subset adenocarcinoma. CONCLUSION: In this exploratory study using retrospective data, trends were found for lung cancer diagnosis with brain metastatic disease, appearing more common in the military sample from a single-center relative to previously published estimates in the general population. Rates were similar for adenocarcinoma. More research into the higher frequency of lung cancer in the military population compared to the general population should be further explored.
CTNI-61. PILOT STUDY OF REPEATED PLANNED GLUCARPIDASE FOLLOWING HIGH DOSE METHOTREXATE (HD-MTX) IN CNS LYMPHOMA (CNSL)
Authors: Lauren Schaff, Mina Lobbous, Ugur Sener, Igor Gavrilovic, Alexandra Miller, Jacqueline Stone, Anna Piotrowski, Anna Skakodub, Juli Madzsar, Alyssa Schumpp, Edward Acosta, Kevin Ryan, Dean Carlow, Lisa DeAngelis, Louis Nabors, Christian Grommes
Journal: Neuro-Oncology (2020)

Abstract This study explores the repeated use of glucarpidase following HD-MTX in patients with CNSL. HD-MTX requires aggressive hydration and inpatient monitoring to prevent toxicity. Glucarpidase 50 units(u)/kg for delayed MTX clearance results in a reduction of systemic MTX levels without crossing the blood brain barrier. This study explores the use of 1000 or 2000 units of glucarpidase following repeated cycles of MTX 3–8 g/m2. Eligible adult patients had isolated CNSL, CrCl ≥ 60 mL/min, and KPS ≥ 50. Rituximab with MTX was administered for eight cycles. Glucarpidase was given 24 hours after each MTX infusion. MTX concentrations were monitored in serum and cerebrospinal fluid (CSF). Twelve patients enrolled to date and data are available for 50 doses of MTX (3 g/m2 (20), 6 g/m2 (21), 8 g/m2 (9)). Glucarpidase 1000u (14) or 2000u (36) resulted in at least a 95% reduction in serum MTX levels within 15 minutes following 49/50 doses. A 93% decrease was seen with the remaining dose. Glucarpidase was not detected in the CSF of 7 patients analyzed. Potentially cytotoxic MTX concentrations (10–6 M) were observed in CSF 1 hour (7/7) and 6 hours (4/7) after glucarpidase administration. Radiographic responses are evaluable in 9 patients: complete response (5), partial response (2), stable disease (1), and progressive disease (1). No grade 3 events were attributed to glucarpidase; one grade 4 event of anaphylaxis occurred. Anti-glucarpidase antibodies were detected in 2/5 patients analyzed. In summary, administration of low-dose glucarpidase 24 hours after MTX 3–8 g/m2 results in a reproducible rapid reduction in serum MTX levels in non-renally impaired patients. CSF MTX levels remain therapeutic and clinical response expected from MTX-based therapy does not appear compromised. Anti-glucarpidase antibodies may develop though significance remains unclear. Study is ongoing. Future directions will explore glucarpidase use for reduction of inpatient stay with HD-MTX.
Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial
Authors: Jacqueline Halton, Leonardo R Brandão, Matteo Luciani, Lisa Bomgaars, Elizabeth Chalmers, Lesley G Mitchell, Ildar Nurmeev, Anjali Sharathkumar, Pavel Svirin, Kirill Gorbatikov, Igor Tartakovsky, Monika Simetzberger, Fenglei Huang, Zhichao Sun, Jörg Kreuzer, Savion Gropper, Paul Reilly, Martina Brueckmann, Manuela Albisetti, Ildar Nurmeev, Asiya Safina, Ondrej Zapletal, Leonardo R Brandão, Tomas Kuhn, Tomas Votava, Judy Felgenhauer, Anjali Sharathkumar, Pavel Svirin, Ali Amid, Jacqueline Halton, Kirill Gorbatikov, Paola Saracco, Csongor Kiss, Susan Halimeh, Madlen Reschke, Beate Wulff, Michele David, Zbynek Novak, Inna Trunina, Manuela Albisetti, Tony Frisk, Heidi Glosli, Andreas Groll, Olga Lvova, Ilgen Sasmaz, Darintr Sosothikul, Virginija Zilinskaite, Erin Cockrell, Valeriy Digtyar, Ivana Hadacova, Sauli Palmu, Anjali Pawar, Joyce Maria Annichino Bizzacchi, Umran Caliskan, Tiraje Celkan, Dmytro Dmytriiev, Colleen Harkins Druzgal, Graciela Onelda Elena, Antonis Kattamis, Ramazan Kaan Kavakli, Christoph Male, Nihal Ozdemir, An Van Damme, Tatiana Zvereva, Aanen Aarli, Rogelio Alejandro Paredes Aguilera, Selin Aytac, Jorge Carneiro, Antonio Chistolini, Maria Gabriela Mazzucconi, Fernando Corrales-Medina, Francis Couturaud, Stacey E Croteau, Cameron Trenor III, Michael Damgaard, Natalia Dixon, Anna Galustyan, Jiri Hak, Marianne Hoffmann, Alphan Kupesiz, Veerle Labarque, Christel van Geet, Ming-Chih Lin, Yun-Ching Fu, Sandra Loggetto, Veerle Mondelaers, Irena Odri-Komazec, Shoshana Revel-Vilk, Julian Sevilla, Luciano Fuzzato Silva, José Kerr Saraiva, Fernando Felix Montes Tapia, Wendy Woods-Swafford
Journal: The Lancet Haematology (2020)
56P Efficacy and safety of nivolumab (Nivo) in recurrent and/or metastatic platinum-refractory squamous cell carcinoma of head and neck (R/M SCCHN): A real-world data study
Authors: J.J. Soto Castillo, J. Esteban Villarrubia, P. Alvarez Ballesteros, P. Garrido Lopez, A. Soria Rivas
Journal: Annals of Oncology (2020)
NFB-16. mTOROPATHIES AND SUBEPENDYMAL GIANT CELL ASTROCYTOMAS: PREDICTIVE VALUE OF GERMINAL TSC1/2 MUTATIONS SCREENING IN FAMILIAL CASES
Authors: Nouha Bouayed Abdelmoula, Walid Smaoui, Balkiss Abdelmoula, Samir Aloulou, Imen Masmoudi, Imen Bouaziz, Ines Lamloum, Hadil Chaari, Asma Yaich, Rafik Dhouib, Sonia Sellami, Mariem Keskes, Sourour Fellah, Khawla Khlifi, Amir Medhioub, Nabil Mhiri
Journal: Neuro-Oncology (2020)

Abstract mTOR controls several important aspects of cell function particularly in the nervous system. Its hyperactivation has been involved in tuberous sclerosis complex (TSC) and other mTORopathies as well as drug-resistant epilepsy. Mutations in TSC1 and TSC2 genes cause loss of normal inhibition of mTORC1 complex, leading to cell overgrowth and disruptions in synaptogenesis. Many children and adults with TSC harbour neurologic defects especially subependymal giant cell astrocytomas (SEGAs) in the brain. Here, we have performed mutational analysis followed by a genetic counselling for a Tunisian family from Sfax town harboring epileptic seizures associated to a neurocutaneous disorder. Index cases were referred for renal angiolipomas (RAL) associated to seizures crisis and were diagnosed as having TSC. The first 26-year-old patient complained of epilepsy since the age of 22 with left temporal crisis related to cortical tubers near the Heschl’s gyrus. His brother, a 36-year-old man presented more severe epileptic crisis (since 15 years-old), multiples RAL, subependymal nodules, and a rapid evolution of his mTORopathy with tumoral progression of his renal and central nerve lesions: renal cell carcinoma and SEGAs. TSC1 gene mutation screening showed heterozygous two bp deletion at codons 213 and 214 of exon 5. SEGAs are rare, low-grade glioneuronal brain tumors that occur almost exclusively in TSC patients but can lead to nervous complications. We showed through this report, the predictive value of germinal TSC mutations screening in familial cases, because early recognition of the molecular defect may lead to appropriate management of the tumoral progression.
EPID-18. TRENDS IN INCIDENCE AND SURVIVAL OF MALIGNANT PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS IN THE NETHERLANDS
Authors: Raoull Hoogendijk, Jasper van der Lugt, Dannis van Vuurden, Eelco Hoving, Leontien Kremer, Pieter Wesseling, Henrike Karim-Kos
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Variation in survival of pediatric central nervous system (CNS) tumors is large between countries. Within Europe, the Netherlands had one of the worst reported survival rates of malignant CNS (mCNS) tumors during 2000–2007. METHODS Using the Netherlands Cancer Registry, we evaluated trends in incidence and survival of pediatric mCNS tumors (behavior /3, 5th digit in the morphology code) diagnosed between 1990–2017. RESULTS 839 newly-diagnosed mCNS tumor patients &amp;lt;18 years were registered between 1990–2017. Incidence of mCNS tumors remained stable (average incidence rate, 21.6 per million person-years). However, an increased incidence of malignant gliomas, NOS was found (Estimated Annual Percentage Change (EAPC) 11.6% p&amp;lt;0.001). This appears to be related to a registration shift between 1990–1999 and 2000–2009 as brainstem tumors increased (+25%, n=79) for astrocytomas and other gliomas but decreased (-31%, n=32) for unspecified intracranial and intraspinal neoplasms. Overall, 5-year observed survival (5Y-OS) of mCNS tumors increased from 51% in 1990–1999 to 61% in 2010–2017 (P-for-trend&amp;lt;0.001). This increase was not constant over time, as 5Y-OS for the period 2000–2009 was 47%. The only significant decrease in survival was found for malignant astrocytomas and other gliomas with a 5Y-OS of 56% in 1990–1999 decreasing to 48% in 2010–2017 (P-for-trend&amp;lt;0.001). CONCLUSION Between 1990–2017 incidence of mCNS tumors in the Netherlands remained stable and survival increased. However, a decrease in survival was seen for malignant astrocytomas and other gliomas, which is partially explained by the registration shift of brainstem tumors. The impact of this shift on survival for all mCNS tumors is subject to further research.
MBRS-23. SIGNIFICANCE OF mi-R33 IN GENERATION AND PROGRESSION OF MEDULLOBLASTOMA
Authors: Yasuzumi Matsui
Journal: Neuro-Oncology (2020)

Abstract Lipid metabolism has been shown to be associated with tumorigenicity in various malignancies. The purpose of this study was to investigate the association of miR-33, a key regulator of lipid metabolism, in tumorigenicity and progression of medulloblastoma. miR-33a is an only isotype of miR-33 in rodents although miR-33b is also detected in human. Incidence of medulloblastoma and histopathological findings were compared between ptch1+/- mice and ptch1+/- miR-33a-/- mice. Effect of miR-33b upregulation by cordycepin was tested in DAOY medulloblastoma cells both in vitro and in vivo. Knockout of miR-33a in ptch1+/- transgenic mouse model increased the incidence of spontaneous generation of medulloblastoma from 19.8% to 49.5% (p &amp;lt; 0.001) at 10 months. Cordycepin, which upregulates miR-33b, prevented tumor growth in DAOY human medulloblastoma cell line, but the effect was not evident in an orthotopic mouse medulloblastoma model. Although miR-33 seems to be an important regulator of medulloblastoma, treatment efficacy of cordycepin was not enough. Combination treatment with immunotherapy or cytotoxic treatment needs to be tested to show survival benefit in preclinical models.
QOLP-21. A PRELIMINARY REPORT ON QUALITY OF LIFE AND SEXUAL FUNCTION IN BRAIN CANCER PATIENTS
Authors: Maria Boccia, Elizabeth Anyanda, Ekokobe Fonkem
Journal: Neuro-Oncology (2020)

Abstract As cancer treatment has advanced, quality of life (QoL) has become a significant consideration in patient and survivor care. The 2005 Institute of Medicine Cancer Survivorship Care Planning guide requires the inclusion of information on the possible effects of cancer on marital/partner relationship and sexual functioning, among other factors related to QoL. The purpose of this study is to explore the rates and types of sexual dysfunction among brain cancer patients. Patients were recruited from a neuro-oncology practice and given a QoL questionnaire (FACT-Br). Women were given the Female Sexual Function Index (FSFI). Men were given scales to assess premature ejaculation (PE), erectile dysfunction (ED), and Peyronie’s disease. In addition, information about site and type of tumor and treatment (surgery, radiation, chemotherapy) was collected. Descriptive statistics as well as T-tests and ANOVAs were used to analyze the data. Data were collected from 50 patients. The most common form of brain tumor in this sample was glioblastoma. The frontal lobe was the most common location of tumors. There was significantly more sexual dysfunction than previously reported, with 66% of the sexually active women meeting criteria for total FSFI. Of the men who were sexually active, 60% reported some ED and 80% reported PE. QoL measures were correlated with sexual dysfunction. Our capacity to address sexual function concerns of patients is dependent on our understanding the types of difficulties encountered. This study provides preliminary information about the effect of brain cancer diagnosis and treatment on a major contributor to QoL in these patients.