tbuckley/cabot-search huggingface dataset:
Covid-19: Transparency and communication are key
Authors: Fiona Godlee
Journal: BMJ (2020)

As the first wave of covid-19 vaccination gets under way, the need for good communication has never been greater. Without it, the extraordinary scientific advances that have led to the vaccines’ development might easily be derailed. Clumsy political jingoism almost hijacked the UK’s rapid approval of the Pfizer vaccine. But the regulator has made it clear that, despite giving emergency temporary authorisation, all the usual procedures were followed.1

Now we need to make sure that the vaccination programme is implemented well, say Azeem Majeed and Mariam Molokhia, avoiding the …
CTIM-30. EFFICACY OF PEMBROLIZUMAB IN PATIENTS WITH PITUITARY CARCINOMA: RESULTS FROM A PHASE II STUDY
Authors: Nazanin Majd, Steven Waguespack, Janku Filip, Siqing Fu, Marta Penas-Prado, Mingxuan Xu, Anas Alshawa, Carlos Kamiya-Matsuoka, Shaan Raza, Ian McCutcheon, Naing Aung
Journal: Neuro-Oncology (2020)

Abstract Pituitary carcinoma is an aggressive tumor characterized by metastatic spread beyond the sellar region that leads to debilitating symptoms and poor survival. Pituitary carcinomas recur despite conventional multimodality treatments. Given the recent advances in the use of immune checkpoint inhibitors (CPIs) to treat various solid cancers, there is interest in exploring the role of immunotherapy for treating aggressive, refractory pituitary tumors. We treated four pituitary carcinoma patients with pembrolizumab as part of a phase II clinical trial (NCT02721732). Here, we present their clinical course and outcomes and correlate responses with available molecular data: hypermutation status, PD-L1 staining, tumor-infiltrating lymphocyte score, microsatellite status and tumor mutational burden. Patients 1 and 2, with heavily pretreated, refractory corticotroph pituitary carcinoma, had partial radiographic (60% and 32% per irRECIST, respectively) and hormonal responses. Patient 1’s response continues 42 months after initiation of pembrolizumab and his baseline tumor tissue obtained after treatment with temozolomide demonstrated a hypermutator phenotype with MSH2 and MSH6 gene mutations. Patient 2’s tumor was not sampled after exposure to temozolomide, but prior somatic mutational testing was negative. Patient 3 (non-functioning corticotroph tumor) had a best response of stable disease for four months. Patient 4 (prolactin-secreting carcinoma) had progressive disease. The latter two patients’ tumors did not demonstrate a hypermutator phenotype after treatment with temozolomide. PD-L1 staining was negative in all tumors. TIL score was 2 in Patients 1 and 4, negative in Patient 3 and not available in Patient 2. All patients tolerated the treatment well with mild adverse events. Our study generates the hypothesis that an alkylating agent-induced hypermutator phenotype may be an indicator of response to CPIs in pituitary carcinomas. The role of CPI in treating patients with pituitary carcinoma and mechanisms of hypermutation in this population require further study.
PATH-45. CLINICAL UTILITY OF COMBINED NEXT GENERATION SEQUENCING AND CHROMOSOMAL MICROARRAY ANALYSIS FOR THE DIAGNOSIS AND MANAGEMENT OF ADULT GLIOMAS
Authors: Corinne Praska, Thomas Kollmeyer, Emily Barr Fritcher, Jesse Voss, Michelle McKenna, Jessica Balcom, Amber Pryzbylski, Romela Pasion, Benjamin Kipp, Aditya Raghunathan, Rachael Vaubel, Jeanette Eckel Passow, Daniel Lachance, Cristiane Ida, Caterina Giannini, Robert Jenkins
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Molecular parameters have been incorporated into the 2016 WHO Classification of CNS Tumors and subsequent cIMPACT-NOW updates to facilitate clinical management of glioma patients. However, there have been few reports of the overall clinical utility of comprehensive genetic testing in adult glioma patients. We report the results of sequencing and chromosomal microarray analysis of adult gliomas seen at the Mayo Clinic and through the Mayo Clinic Laboratories (MCL) reference practice. METHODS A consecutive series of 379 Mayo Clinic adult glioma patients were consented to receive targeted next generation sequencing and chromosomal microarray analysis, regardless of standard clinical ordering practices. Known diagnostic, prognostic, and predictive alterations were annotated for each case. These results were compared to the larger MCL reference practice of 2400 adult glioma samples that received one or both tests clinically. RESULTS Of the consecutive Mayo Clinic cases, 67% had alterations that fell into at least one of the diagnostic, prognostic, and/or predictive categories. Molecular testing generated diagnostic, prognostic, and predictive information in 44%, 34%, and 36% of cases, respectively. Diagnostically, molecular testing mainly aided in arriving at a final integrated diagnosis, and only a small number of cases (n= 5; 1%) had a change in diagnosis. The consecutive cases represent the typical distribution of adult glioma types (47% IDH-wildtype glioblastoma/astrocytoma, 22% IDH-mutant astrocytoma/glioblastoma, 13% IDH-mutant 1p/19q-codeleted oligodendroglioma, and 18% other tumor types). The MCL practice is enriched in tumors with atypical molecular patterns (37% IDH-wildtype glioblastoma/astrocytoma, 17% IDH-mutant astrocytoma/glioblastoma, 18% IDH-mutant 1p/19q-codeleted oligodendroglioma, and 29% other tumor types). CONCLUSIONS Molecular testing provides useful diagnostic, prognostic, and predictive information for the clinical management of adult glioma patients. While the current guidelines for ordering molecular testing are effective for diagnostic purposes, additional prognostic and predictive information can be gleaned from comprehensive molecular testing of adult gliomas.
EPID-19. RACIAL/ETHNIC DISPARITIES IN TREATMENT PATTERN AND TIME TO TREATMENT FOR ADULTS WITH GLIOBLASTOMA IN THE US
Authors: Quinn Ostrom, Nirav Patil, Gino Cioffi, Jill S Barnholtz-Sloan
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Race/ethnicity have been previously shown to significantly affect survival after diagnosis with glioblastoma, but the cause of this survival difference is not known. The aim of this study was to examine variation in treatment pattern and time to treatment by race/ethnicity, and the extent to which this affects survival. METHODS Data were obtained from the National Cancer Database (NCDB) for adults &amp;gt;= 40 with glioblastoma (histologic codes 9440–9442 and topographical codes C71.0–C71.9) from 2004–2016 (N=117,710). Treatment patterns and time to treatment by race/ethnicity were compared using univariable and multivariable logistic and linear regression models, respectively. Models were adjusted for age, sex, insurance status, pre-existing comorbidities, type of treating institution, and distance to institution. RESULTS Black non-Hispanics (BNH) were 17% less likely to receive radiation (p=1.47x10-8) and 32% less likely to receive chemotherapy (p=1.10x10-31) than White non-Hispanics (WNH). Among those that did receive treatment, it took 3.3 additional days on average for BNH to receive radiation (p=2.12x10-11) and 4.6 additional days to receive chemotherapy in comparison to WNH (p=4.14x10-10). Hispanics were 21% less likely to receive radiation (p=4.79x10-12), and 23% less likely to receive chemotherapy (p=7.51x10-14) than WNH. Among those that did receive treatment, it took 3.3 additional days on average for Hispanics to receive radiation (p=4.07x10-9) and 4 additional days to receive chemotherapy in comparison to WNH (p=1.51x10-6). There were no significant differences in time to surgery, or in to treatment for Asian Pacific Islanders or American Indian/Alaska Natives. CONCLUSIONS Both likelihood of receiving treatment and time to radiation and chemotherapy vary significant between BNH and Hispanics as compared to WNH, and this difference is not fully explained by comorbidities or access to health care.
Covid-19: EU countries spent over €220m stockpiling remdesivir despite lack of effectiveness, finds investigation
Authors: Lucien Hordijk, Priti Patnaik
Journal: BMJ (2020)

The drug's manufacturer was aware of the negative results of the Solidarity trial before the European Commission struck a procurement deal with it, finds an investigation by <b>Lucien Hordijk</b> and <b>Priti Patnaik</b>
ETMR-12. EMBRYONAL TUMOR WITH MULTILAYERED ROSETTES: A SINGLE CENTER EXPERIENCE
Authors: Sodai Yoshimura, Masahiro Sugawa, Kohei Fukuoka, Makiko Mori, Yuki Arakawa, Masao Kobayashi, Yutaka Tanami, Atsuko Nakazawa, Katsuyoshi Koh, Jun Kurihara
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Embryonal tumor with multilayered rosettes (ETMR) is a rare, highly malignant tumor of the central nervous system and is usually diagnosed in children aged &amp;lt;2 years. Currently, because no defined treatment strategy has been reported, treatment regimens are often extrapolated from other embryonal tumors. Therefore, data collection of ETMR cases is important for further understanding EMTR. Here, we present our experience with four patients with ETMR. MATERIAL AND METHODS Patients with a pathological diagnosis of ETMR from 1999 to 2016 at Saitama Children’s Medical Center were included. Their clinical data were retrospectively analyzed. RESULTS This study included four cases of ETMR (one male and three females). The mean age at diagnosis was 29.5 (range, 15–37) months. Presenting symptoms included seizure, hemiparesis, vomiting, and headache. The mean maximal tumor diameter was 42.5 mm. The tumor locations included frontal lobe, temporal lobe, occipital lobe, cerebellum, and brainstem. Gross total resection was achieved in two cases. Fluorescence in situ hybridization analysis demonstrated amplification of 19q13.42 chromosome region in all cases, and diffuse positive expression was observed in the immunohistochemical staining for LIN28A. Systemic postoperative chemotherapy was administered to all patients. Three patients received intrathecal therapy and three were irradiated. The mean overall survival and progression-free survival were 45.3 and 42 months, respectively. Two patients who underwent gross total resection are alive without recurrence. CONCLUSION Complete surgical resection may be an important prognostic factor in patients with ETMR. Further prospective studies are needed to confirm these results.
Development and dissemination of infectious disease dynamic transmission models during the COVID-19 pandemic: what can we learn from other pathogens and how can we move forward?
Authors: Alexander D Becker, Kyra H Grantz, Sonia T Hegde, Sophie Bérubé, Derek A T Cummings, Amy Wesolowski
Journal: The Lancet Digital Health (2020)

The current COVID-19 pandemic has resulted in the unprecedented development and integration of infectious disease dynamic transmission models into policy making and public health practice. Models offer a systematic way to investigate transmission dynamics and produce short-term and long-term predictions that explicitly integrate assumptions about biological, behavioural, and epidemiological processes that affect disease transmission, burden, and surveillance. Models have been valuable tools during the COVID-19 pandemic and other infectious disease outbreaks, able to generate possible trajectories of disease burden, evaluate the effectiveness of intervention strategies, and estimate key transmission variables. Particularly given the rapid pace of model development, evaluation, and integration with decision making in emergency situations, it is necessary to understand the benefits and pitfalls of transmission models. We review and highlight key aspects of the history of infectious disease dynamic models, the role of rigorous testing and evaluation, the integration with data, and the successful application of models to guide public health. Rather than being an expansive history of infectious disease models, this Review focuses on how the integration of modelling can continue to be advanced through policy and practice in appropriate and conscientious ways to support the current pandemic response.
LINC-40. VERY YOUNG PATIENTS AND CENTRAL NERVOUS SYSTEM TUMORS: A SINGLE-CENTER EXPERIENCE IN AN UPPER-MIDDLE-INCOME COUNTRY
Authors: Claudia Madrigal-Avila, Alfonso Perez-Bañuelos, Martin Perez-Garcia, Rafael Ruvalcaba-Sanchez, Lourdes Vega-Vega, Gabriela Escamilla-Asiain
Journal: Neuro-Oncology (2020)

Abstract Tumors of the central nervous system comprise nearly a quarter of all childhood cancers and are the most frequent solid tumor in the pediatric population. Primary central nervous system tumors (PCNST) are a rare and heterogeneous group of tumors responsible for high mortality and morbidity. Around 10% of primary CNS tumors occur during the first year of life with almost half of them during the first six months. About 18% of these tumors appear before the age of two years. Very young children differ from older children and adolescents regarding the incidence and location of different histological entities of CNS tumors. We aimed at providing descriptive epidemiological data and report the outcome in a tertiary center from December 2013 to January 2020 for all histological subtypes of primary central nervous system tumors in very young patients, defined as patients younger than three years. We collect data from 19 patients treated in an oncology exclusive tertiary center in Mexico between 2013 and 2020. This study aims to relate factors such as age, radiotherapy, surgery, chemotherapy with Lansky Performance Scale and determine the impact, not only in the overall survival but also in the quality of life.
EXTH-14. A NOVEL LONG-ACTING INTERLEUKIN-7 AGONIST, NT-I7, INCREASES CYTOTOXIC CD8 CELLS AND ENHANCES SURVIVAL IN MOUSE GLIOMA MODELS
Authors: Subhajit Ghosh, Ran Yan, Sukrutha Thotala, Arijita Jash, Anita Mahadevan, Tong Hu, Byung Ha Lee, Se Hwan Yang, Dennis Hallahan, Milan Chheda, Dinesh Thotala, Jian Campian
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Patients with glioblastoma (GBM) are treated with radiation (RT) and temozolomide (TMZ). These treatments can cause prolonged severe lymphopenia, which is associated with shorter survival. NT-I7 (efineptakin alfa) is a long-acting recombinant human IL-7 that supports the proliferation and survival CD4+ and CD8+ cells in both human and mice. We tested whether NT-I7 would protect T cells from treatment-induced lymphopenia and improve survival. METHODS C57BL/6 mice bearing intracranial tumors (GL261 or CT2A) were treated with RT (1.8 Gy/day x 5 days), TMZ (33 mg/kg/day x 5 days) and/or NT-17 (10 mg/kg on the final day of RT completion). We followed for survival and profiled CD3, CD8, CD4, FOXP3 in peripheral blood over time. In parallel, we assessed cervical lymph nodes, bone marrow, thymus, spleen, and the tumor 6 days after NT-I7 treatment. RESULTS Median survival in mice treated with NT-I7 combined with RT was significantly better than RT alone (GL261: 40d vs 34d, p&amp;lt; 0.0021; CT2A: 90d vs 40d, p&amp;lt; 0.0499) or NT-I7 alone (GL261: 40d vs 24d, p&amp;lt; 0.008; CT2A: 90d vs 32d, p&amp;lt; 0.0154). NT-17 with RT was just as effective as NT-I7 combined with RT and TMZ in both GL261 (40d vs 47d) and CT2A (90d vs 90d). NT-I7 treatment significantly increased the amount of CD8+ cells in the peripheral blood and tumor. NT- I7 rescued CD8+ T cells from RT induced lymphopenia in peripheral blood, spleen, and lymph nodes. NT-I7 alone or NT-I7 in combination with RT increased the CD8+ T cells in peripheral blood and tumor while reducing the FOXP3+ T-reg cells in the tumor microenvironment. CONCLUSIONS NT-I7 protects T-cells from RT induced lymphopenia, improves cytotoxic CD8+ T lymphocytes systemically and in the tumor, and improves survival. Presently, a phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).
DDEL-13. FOCUSED ULTRASOUND MEDIATED BLOOD BRAIN BARRIER DISRUPTION IN A MURINE MODEL OF PONTINE GLIOMA: A SAFETY AND FEASIBILITY STUDY
Authors: Zachary Englander, Hong-Jian Wei, Antonios Pouliopoulos, Pavan Upadhyayula, Chia-Ing Jan, Eleonora Spinazzi, Peter Canoll, Jeffrey Bruce, Neil Feldstein, Stergios Zacharoulis, Elisa Konofagou, Cheng-Chia Wu
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Drug delivery remains a major obstacle in DIPG, as the blood brain barrier (BBB) limits the penetration of systemic therapies to the brainstem. Focused ultrasound (FUS) is an exciting new technology that, when combined with microbubbles, can open the BBB permitting the entry of drugs across the cerebrovasculature. Given that the utility of FUS in brainstem tumors remains unknown, the purpose of our study was to determine the safety and feasibility of this technique in a murine pontine glioma model. METHODS A syngeneic orthotopic model was established by stereotactic injection of PDGF-B+PTEN-/-p53-/- murine glioma cells (10,000/1ul) into the pons of B6 albino mice. A single-element, spherical-segment FUS transducer (center frequency=1.5MHz) driven by a function generator through a power amplifier (acoustic pressure=0.7MPa) was used with concurrent intravenous microbubble injection (FUS+MB) to sonicate the tumor on post-injection day 14. BBB opening was confirmed with gadolinium-enhanced MRI and Evans blue. Kondziela inverted screen (KIS) testing was completed to measure motor function. Mice were either immediately sacrificed for histopathological assessment or serially monitored for survival. RESULTS In mice treated with FUS (n=11), there was no measured deficit in KIS testing. Additionally, the degree of intra-tumoral hemorrhage and inflammation on H&amp;E in control (n=5) and treated mice (n=5) was similar. Lastly, there was no difference in survival between the groups (control, n=6, median=26 days; FUS, n=6, median=25 days, p&amp;gt;0.05). CONCLUSION FUS+MB is a safe and feasible technique to open the BBB in a preclinical pontine glioma model.
Abstract 19895: Safety of Subintimal vs. Intraluminal Endovascular Technique for Aorto-Iliac Chronic Total Occlusion
Authors: Kazuki Haraguchi, Yoshiaki Shintani, Tomohiro Kawasaki, Masato Nakamura
Journal: Circulation (2017)

Introduction: Endovascular therapy (EVT) for aorto-iliac (AI) artery disease is widely accepted. However, recanalization of chronic total occlusion (CTO) is still challenging and technical success ...
QOLP-29. INFORMATION ON HEADACHE FOR BRAIN TUMOR PATIENTS ON INTERNET – GUIDING OR MISLEADING?
Authors: Merja Kallio
Journal: Neuro-Oncology (2020)

Abstract Patients often consult the internet if they suspect a brain tumor. Migraine and tension type headache have an active prevalence of round 50%. 96% of the general population has had some kind of headache during their lifetime. There are many possible exacerbating factors for precipitating or worsening headache. Consequently headache makes many people suspect a brain tumor. Nowadays when MRI and CT are widely available making earlier diagnosis of brain tumors possible, it has been discovered that in adults headache is rarely the most important or even existing symptom. Nelson and Taylor (1) find headache in 2% of brain tumor patients and Posti et al (2) found it in 20% of glioma patients as presenting symptom but never as a sole symptom. What is the information the patients get on the internet sites? In order to find out the author analyzed 36 webpages concerning headache and brain tumors by brain tumor and cancer societies, Neuro-oncology clinics, University clinics and general health information pages in 4 different languages (Finnish, English, Swedish and German). On 13 of these 36 pages headache was considered the presenting or main symptom. Particularly different cancer and brain tumor societies (8 of 9) explain that headache is the main symptom. On some pages it was concluded that brain tumor patients often have headache but headache patients seldom brain tumors. This is obviously true but does not help patients much. Consequently many of these information sites give patients somewhat vague or even misleading information. This will cause unnecessary anxiety, fear and visits to healthcare. We should strive to make patient information both more clear and more accurate. In order to accomplish this we need more information of the current situation.
CTNI-64. MATRIX REGIMEN FOR NEWLY DIAGNOSED PRIMARY DIFFUSE B-CELL LYMPHOMA OF THE CENTRAL NERVOUS SYSTEM
Authors: Richard Green, Colleen Thornton
Journal: Neuro-Oncology (2020)

Abstract We report our experience treating 16 patients with newly diagnosed primary diffuse B-cell lymphoma of the central nervous system with the MATRix regimen as reported by Ferreri, et al in 2016. The median age was 66 years (y); 8 patients were men and 8 were women. Fourteen had cerebral mass lesions, 1 had a paraspinal mass, and 1 leptomeningeal disease. Treatment consisted of 4 cycles of rituximab 375 mg/sq m (Days 1, 6); methotrexate 3.5 g/sq m (Day 2); cytarabine 2 g/sq m every 12 h (Days 3, 4); and thiotepa 30 mg/sq m (Day 5). Patients without disease progression received carmustine 400 mg/sq m and thiotepa 4 X 5 mg/kg followed by autologous bone marrow transplantation. Four patients were switched to MATRix after 6 cycles of methotrexate and rituximab and received only 2 initial cycles including cytarabine and thiotepa. Overall, 12 patients completed initial chemotherapy. Eleven of these 12 went on to transplantation; one patient had early disease progression and did not proceed to transplantation. All 4 patients over 70 y died early after 1–2 cycles; the median age of these was 80 y, and the causes of early death were neutropenic fever, septic thrombophlebitis, and cardiac arrest. One patient who completed the entire regimen including transplantation died of fungal pneumonia; the other 11 experienced no serious acute toxicity. One patient had late disease progression; one developed symptomatic leukoencephalopathy. Nine of the 16 patients remain alive. At a median follow-up of 23 months, median time to progression was 421 days and overall survival 564 days. These preliminary data suggest that the MATRix regimen in safe and highly effective in the newly diagnosed setting. However, the high incidence of early death in patients over 70 y suggests that the regimen may be too toxic for elderly individuals.