tbuckley/cabot-search huggingface dataset:
DIPG-74. RE-IRRADIATION OF DIPG: DATA FROM THE INTERNATIONAL DIPG REGISTRY
Authors: Lucie Lafay-Cousin, Adam Lane, Austin Schafer, Raya Saab, Sylvia Cheng, Pratiti Bandopadhayay, Mohamed Zaghloul, Motasem El-Ayadi, Kathleen Dorris, Roger Packer, Lindsey Kilburn, Jane Minturn, Andrew Dodgshun, Sara Parkin, Mercedes Garcia Lombardi, Kenneth Cohen, David Gass, Stewart Goldman, Eric Sandler, Katherine Warren, Robert Greiner, Nicholas Gottardo, Hetal Dholaria, Tim Hassall, Scott Coven, Jordan Hansford, Yvan Samson, Sarah Leary, Ute Bartels, Eric Bouffet, Jie Ma, Christopher Tinkle, Michelle Monje-Deisseroth, Paul Fisher, Karen Tsui, David Ziegler, Murali Chintagumpala, Sridharan Gururangan, Lars Wagner, Carl Koschmann, Mariko DeWire-Schottmiller, James Leach, Blaise Jones, Christine Fuller, Rachid Drissi, Brooklyn Chaney, Katie Black, Maryam Fouladi, Douglas Strother
Journal: Neuro-Oncology (2020)

Abstract PURPOSE To review data from DIPG Registry patients recorded to have received a second course of radiation therapy (rRT). METHODS The International DIPG Registry was searched for patients with DIPG who were treated with a known dose of rRT. Doses of rRT, timing from initial diagnosis and primary radiation therapy (pRT), radiographic response to rRT and survival from diagnosis (OS) were evaluated. RESULTS Sixty (11.2%) of 535 Registry patients underwent rRT; dose was provided for 44 patients. Median (range) data from those 44 revealed that rRT was given at 12 (2–65) months from initial diagnosis of DIPG and at 9.6 (1–61) months from completion of pRT at a dose of 26.7 (1.8–74) Gy. After completion of rRT, MRI showed response, progression, stable disease or was not available in 19, 8, 3 and 14 patients, respectively. Median PFS and OS were 11 and 18.1 months, respectively. 475 Registry patients did not undergo rRT; their ages, duration of symptoms, and primary treatment with or without chemotherapy were not significantly different from the rRT cohort. Median PFS and OS for the non-rRT patients were 6.9 and 10 months, respectively. rRT patients were more likely to have had radiographic evidence of tumor necrosis at diagnosis than non-rRT patients. CONCLUSIONS Administration of rRT to patients with DIPG has been inconsistent with respect to timing and dose. Toxicity, response and quality of life data are incomplete, but survival appears to be lengthened with rRT. Prospective clinical trials will elucidate benefits and risks of rRT.
Controversies in the Management of Early-Stage Hodgkin Lymphoma
Authors: Ranjana H. Advani
Journal: Journal of the National Comprehensive Cancer Network (2020)

Early-stage Hodgkin lymphoma is a highly curable malignancy, but controversies surrounding treatment recommendations persist due to the sheer number of treatment choices available, as well as the effort to balance risk versus benefit for each individual patient. The gold standard for treatment has evolved over the years. Currently, in the PET era, fine-tuning therapy approaches is largely focused on avoiding giving too much therapy to patients with a negative interim PET and too little therapy to those with a positive interim PET. Careful patient selection for therapy has become increasingly important, as patient risk factors for early-stage disease are variably defined by German Hodgkin Study Group, EORTC, and NCCN criteria.
TAMI-28. DIFFERENTIAL MIGRATION MECHANICS AND IMMUNE RESPONSES OF GLIOMA SUBTYPES
Authors: Ghaidan Shamsan, Chao Liu, Brooke Braman, Susan Rathe, Aaron Sarver, Nima Ghaderi, Mariah McMahon, Rebecca Klank, Barbara Tschida, Joey McFarren, Jann Sarkaria, H Brent Clark, Steven Rosenfeld, David Largaespada, David Odde
Journal: Neuro-Oncology (2020)

Abstract In Glioblastoma (GBM), tumor spreading is driven by tumor cells’ ability to infiltrate healthy brain parenchyma, which prevents complete surgical resection and contributes to tumor recurrence. GBM molecular subtypes, classical, proneural and mesenchymal, were shown to strongly correlate with specific genetic alterations (Mesenchymal: NF1; Classical: EGFRVIII; Proneural: PDGFRA). Here we tested the hypothesis that a key mechanistic difference between GBM molecular subtypes is that proneural cells are slow migrating and mesenchymal cells are fast migrating. Using Sleeping Beauty transposon system, immune-competent murine brain tumors were induced by SV40-LgT antigen in combination with either NRASG12V (NRAS) or PDGFB (PDGF) overexpression. Cross-species transcriptomic analysis revealed NRAS and PDGF-driven tumors correlate with human mesenchymal and proneural GBM, respectively. Similar to human GBM, CD44 expression was higher in NRAS tumors and, consistent with migration simulations of varying CD44 levels, ex vivo brain slice live imaging showed NRAS tumors cells migrate faster than PDGF tumors cells (random motility coefficient = 30µm2/hr vs. 2.5µm2/hr, p &amp;lt; 0.001). Consistent with CD44 function as an adhesion molecule, migration phenotype was independent of the tumor microenvironment. NRAS and human PDX/MES tumor cells were found to migrate faster and have larger cell spread area than PDGF and human PDX/PN tumors cells, respectively, in healthy mouse brain slices. Furthermore, traction force microscopy revealed NRAS tumor cells generate larger traction forces than PDGF tumors cells which further supports our theoretical mechanism driving glioma migration. Despite increased migration, NRAS cohort had better survival than PDGF which was attributed to enhanced antitumoral immune response in NRAS tumors, consistent with increased immune cell infiltration found in human mesenchymal GBM. Overall our work identified a potentially actionable difference in migration mechanics between GBM subtypes and establishes an integrated biophysical modeling and experimental approach to mechanically parameterize and simulate distinct molecular subtypes in preclinical models of cancer.
LINC-04. POSSIBLE ROLE OF NEOADJUVANT CHEMOTHERAPY IN METASTATIC PURE GERMINOMA IN LOW AND MIDDLE INCOME COUNTRIES. A PRO POS OF A CASE
Authors: Carlos Leal-Cavazos, Paola Escamilla-Luna, Marissa Fernandez-De Luna, Oscar Vidal-Gutierrez
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND CNS germ cell tumors represent about 3–5 % of pediatric brain tumors, 60% are pure germinomas. Germinomas are very sensitive to chemotherapy which has helped to reduce volume and dose of radiotherapy in localized disease while maintaining excellent survival. In metastatic disease the SIOP GCT-96 trial showed no benefit with addition of chemotherapy to craniospinal irradiation alone. Radiotherapy maybe not readily available in Low/Middle Income Countries (LMIC). METHOD We describe a patient in which the use of neoadjuvant chemotherapy helped to rescue vision. The patient is a 9 year old female with a 3 months history of morning headaches and vomits. Visual decline was noticed a month before admission when the child had completely loss vision of the right eye and left eye was partially affected. MRI showed a large suprasellar mass with ventricular nodules. Beta-hGC in CSF was mildly elevated. Patient received 2 cycles of carboplatin/etoposide. After first cycle there was a complete vision recovery in both eyes. After the second course the MRI showed complete response in primary and metastatic disease. Patient received CSI (24Gy + 16 Gy Boost) after 2 cycles of chemotherapy. Chemotherapy was very well tolerated without side effects. Patient vision is 20/20 in both eyes without deficit in visual fields. CONCLUSION Although the addition of chemotherapy in metastatic germinoma has no clear role in reducing radiotherapy it could possible help selected patients in attempt to rescue vision when radiotherapy is not readily available.
INNV-15. COMPARISON OF READIBAND™ ACTIGRAPH AND ASSOCIATED SLEEP/WAKE CLASSIFICATION ALGORITHMS WITH PATIENT-REPORTED SLEEP QUALITY AND FATIGUE IN GLIOBLASTOMA
Authors: Megan Tipps, Meghan Tierney, Caitlin Monson, Kelsey Jackson, Nilanjana Banerji, Amy Ellenberger, John Trusheim
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Fatigue and sleep disturbances are among the most common side-effects reported by patients with glioblastoma and contribute significantly to the quality-of-life for this population. Non-invasive monitoring of long-term sleep patterns and fatigue levels in this population would allow for comparison between iatrogenic sleep disturbances, disease progression, treatment tolerance, and self-reported levels of fatigue. Here, we describe initial results from the implementation of the Readiband™ Sleep Tracker (Fatigue Science), a wearable actigraph device, for monitoring sleep patterns and fatigue in patients with newly diagnosed glioblastoma. PATIENTS AND METHODS Patients were prospectively enrolled and asked to wear the Readiband™ Sleep Tracker for a maximum of twelve months or until disease progression. Patients were also asked to report fatigue levels and sleep quality via the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Pittsburg Sleep Quality Index (PSQI) questionnaires. Demographic, pathologic, and clinical information was abstracted from electronic medical records. RESULTS When data across all participants was combined, FACIT-F and PSQI scores were negatively correlated (r= -0.78, p&amp;lt; 0.001). Significant correlations were also seen between the Readiband™ measures for alertness, sleep quality, and sleep efficiency (p&amp;lt; 0.05 for all). However, we did not observe any correlations between the Redaiband™ measures and subjective survey responses. Interestingly, when patients were sub-divided based on tumor recurrence, we did see significant correlations between both survey scores and sleep quality and sleep efficiency measures (p&amp;lt; 0.05 for all) in patients that recurred during the study period. CONCLUSION The Readiband™ Sleep Tracker is a convenient and viable approach for monitoring sleep and fatigue in glioblastoma patients. Our preliminary findings suggest that actigraph measures may be a better indicator of subjective sleep quality and fatigue levels in specific sub-sets of this population. Ongoing research is exploring other clinical factors that might impact the accuracy of Readiband™ measures.
Abstract 15350: The State of Renal Sympathetic Denervation for the Management of Patients With Hypertension: A Systematic Review &amp; Meta-analysis
Authors: Moinuddin Syed, Mohammed Osman, Hani Alhamoud, Ramesh Daggubti
Journal: Circulation (2020)

Introduction: Sympathetic nervous system plays a central role in the development and persistence of essential hypertension. In recent years Renal Sympathetic Denervation (RSD) has emerged as a promising option for the treatment of patients with hypertension Hypothesis: Despite the availability of multiple anti-hypertensive medications, data from the national health and nutritional survey shows that lifelong polypharmacy is failing as a therapeutic strategy due to lack of awareness and compliance with medications. The significant cost in terms of morbidity and mortality associated with uncontrolled hypertension calls for nonpharmacologic approaches for management. Methods: We conducted a literature search of PubMed, EMBASE, Cochrane library and Clinicaltrials.gov from inception through May 20, 2020. Outcomes of interest were change in 24-hour ambulatory systolic (ASBP) or diastolic blood pressure (ADBP) and change in office systolic (OSBP) or diastolic blood pressure (ODBP). We pooled data from randomized controlled trials (RCTS) comparing RSD to sham procedures in the management of hypertension using the random effect model. Results: A total of 1,363 patients from 8 studies were included in the current meta-analysis. The mean age of the included patients was 56 ± 2.6 years, 29 % were women and the median duration of maximum follow up was 6-month (range 3-12 month). There was more reduction favoring RSD in ASBP (Weighted mean difference (WMD) -3.55; 95%CI -4.91 - -2.19, p&lt;0.001, I 2 =0%), ADBP (WMD -1.87; 95%CI -3.07 - -0.66, p=0.002, I 2 =43%) , OSBP (WMD -5.5; 95%CI -7.59 - -3.40, p&lt;0.001, I 2 =7%) and ODBP (WMD -3.20; 95%CI -4.47 - -1.94, p&lt;0.001, I 2 =14%). Conclusions: The use of RSD for the management of hypertension resulted in effective reduction in the ambulatory and office blood pressure compared to sham procedure. Adequately powered RCTs of RSD are needed to confirm safety, reproducibility and assess the impact on clinical outcomes.
67P Survival of responders to nivolumab (NIVO) + ipilimumab (IPI) as first-line treatment for advanced NSCLC in CheckMate 227, part 1
Authors: J.R. Brahmer, T-E. Ciuleanu, M. Schenker, C. Audigier-Valette, B. Zurawski, H. Linardou, S-W. Kim, G.A. Otterson, P. Salman, E. De La Mora Jimenez, K. Lesniewski-Kmak, S. Ahmed, I. Albert, F. Barlesi, K. Feeney, N. Frickhofen, A. Li, P. Sun, M. Hellmann
Journal: Annals of Oncology (2020)
NCMP-28. BEVACIZUMAB ASSOCIATED INTRACEREBRAL HEMORRHAGE IN PATIENTS WITH PRIMARY CNS MALIGNANCY
Authors: Nathan Clarke
Journal: Neuro-Oncology (2020)

Abstract The risk of intracranial hemorrhage (ICH) associated with the use of bevacizumab (BEV) has been a topic of several reviews in the literature, and is considered to be a potential adverse effect of BEV when used in patients with malignant glioma. We performed a single-center retrospective chart-review identifying glioma patients treated with BEV at our institution. 595 unique patients who received BEV with documented follow up were identified. Of these patients, 23 (3.9%) developed ICH within 12 weeks (five half-lives) of a BEV infusion (median 9 days post infusion, 1-24 days IQR). There was a trend towards statistical significance between dose administered and the incidence of hemorrhage (P=0.06), with all 23 hemorrhages occurring in patients treated with 10 mg/kg (n=21/490) per infusion or 15 mg/kg per infusion (n=2/35) (n=525, 88.2% of cohort). No patient on dosing regimens of 7.5 mg/kg (n=72) or 5 mg/kg per infusion (n=16) (n=88, 14.7% of cohort) developed ICH. Therapeutic anticoagulation and concomitant BEV therapy was observed in 103 (17%) patients with 10 patients (10/93, 9.7%) developing an ICH (n=10), at a rate significantly higher than in patients treated with bevacizumab alone (13/479, 2.6%) (p=0.0025). When hemorrhages occurred (with or without concomitant anticoagulation) they were associated with high morbidity and mortality (ECOG 3.54 versus 1.26, p = &amp;lt; 0.0001), with 12 patients (52%) suffering severe debility (n=2) or death (n=10). CONCLUSION: Bevacizumab associated intracerebral hemorrhages remain uncommon events, similar to the baseline rate of spontaneous hemorrhage associated with malignant glioma. We observed a trend towards significance with higher doses per infusion associated with an increased rate of intracerebral hemorrhage. The combination of anticoagulation and BEV appears to confer a greater risk of hemorrhage than BEV alone.
SARS-CoV-2 Detected on Environmental Fomites for Both Asymptomatic and Symptomatic Patients with COVID-19
Authors: Minghui Yang, Liang Li, Ting Huang, Shaxi Li, Mingxia Zhang, Yang Yang, Yujin Jiang, Xiaohe Li, Jing Yuan, Yingxia Liu
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
The immune landscape in tuberculosis reveals populations linked to disease and latency
Authors: Ekaterina Esaulova, Shibali Das, Dhiraj Kumar Singh, Jose Alberto Choreño-Parra, Amanda Swain, Laura Arthur, Javier Rangel-Moreno, Mushtaq Ahmed, Bindu Singh, Ananya Gupta, Luis Alejandro Fernández-López, Maria de la Luz Garcia-Hernandez, Allison Bucsan, Chivonne Moodley, Smriti Mehra, Ethel García-Latorre, Joaquin Zuniga, Jeffrey Atkinson, Deepak Kaushal, Maxim N. Artyomov, Shabaana A. Khader
Journal: Cell Host & Microbe (2020)
DDRE-11. DEVELOPMENT OF THE FIRST-IN-CLASS INHIBITOR OF CHD4 - SENSITIZING RESISTANT GLIOMAS
Authors: Elmar Nurmemmedov, Santosh Kesari
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma is a lethal brain tumor with high recurrence rate. CHD4 overexpression, which drives resistance to DNA damage, is one of the major sources of recurrence. Since standard GBM treatments like radiation and temozolomide chemotherapy create DNA damage, inhibition of CHD4 offers a new therapeutic option for resensitizing GBM. CHD4 is a ubiquitously expressed ATP-dependent chromatin remodeler, which plays a crucial role in epigenetic regulation of gene expression and in DNA damage repair. Structurally, CHD4 contains an HMG-like domain, PHD domains, two chromodomains, a catalytic ATPase module, two domains of unknown function (DUF) and a C-terminal domain CHDCT2. Currently, no specific inhibitors targeting this chromatin remodeler have been reported yet. We aim to develop the first-in-class inhibitor targeting chromo-domain of CHD4. We have performed in silico screens to identify small molecules binding to the chromo-domains of CHD4. We present our growing in vitro data demonstrating biophysical properties and mechanism-of-action of these novel inhibitors. We expect that the experiments proposed here will result in the development of the first-in-class CHD4 inhibitor which can be used in the future not only to better study the physiological role of CHD4 but also to determine its potential as a novel targeted therapy for GBM.
53P Studying autoimmune diseases with thymic epithelial tumors (TET): Real-world insight from RYTHMIC
Authors: J.C. Benitez, M-E. Boucher, E. Dansin, M. Kerjouan, I. Bigay-Game, E. Pichon, F. Thillays, P.E. Falcoz, S. Lyubimova, Y. Oulkhouir, F. Calcagno, L. Thiberville, C. Clément-Duchêne, F. Morin, P. Missy, P. Thomas, J. Maury, T. Molina, N. Girard, B. Besse
Journal: Annals of Oncology (2020)
Occupation- and age-associated risk of SARS-CoV-2 test positivity, the Netherlands, June to October 2020
Authors: Brechje de Gier, Priscila de Oliveira Bressane Lima, Rolina D van Gaalen, Pieter T de Boer, Jeroen Alblas, Marc Ruijten, Arianne B van Gageldonk-Lafeber, Toos Waegemaekers, Anja Schreijer, Susan van den Hof, Susan JM Hahné
Journal: Eurosurveillance (2020)

High coronavirus incidence has prompted the Netherlands to implement a second lockdown. To elucidate the epidemic’s development preceding this second wave, we analysed weekly test positivity in public test locations by population subgroup between 1 June and 17 October 2020. Hospitality and public transport workers, driving instructors, hairdressers and aestheticians had higher test positivity compared with a reference group of individuals without a close-contact occupation. Workers in childcare, education and healthcare showed lower test positivity.
Noncardiac Abnormalities in Diagnostic Cardiac Computed Tomography: Within Normal Limits or We Never Looked!⁎⁎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: John A. Rumberger
Journal: Journal of the American College of Cardiology (2006)
Intravital imaging of liposome behavior upon repeated administration: A step towards the development of liposomal companion diagnostic for cancer nanotherapy
Authors: Victor A. Naumenko, Stepan S. Vodopyanov, Kseniya Yu. Vlasova, Daria M. Potashnikova, Pavel A. Melnikov, Daniil A. Vishnevskiy, Anastasiia S. Garanina, Marat P. Valikhov, Anastasiia V. Lipatova, Vladimir P. Chekhonin, Alexander G. Majouga, Maxim A. Abakumov
Journal: Journal of Controlled Release (2020)
IMMU-52. IMMUNE EFFECTOR CELL ASSOCIATED NEUROTOXICITY (ICANS) AMONG PEDIATRIC AND AYA PATIENTS: MD ANDERSON CANCER CENTER EXPERIENCE
Authors: Brandon Brown, Kris Mahadeo, Sajad Khazal, Demetrios Petropoulos, Priti Tewari, John Slopis, Paolo Tambaro, Zsila Sadighi
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Immune effector cell associated neurotoxicity (ICANS) and cytokine release syndrome (CRS) are potentially life-threatening complications associated with immune effector cell (IEC) therapies. We characterize ICANS in pediatric and adult young adolescent (AYA) patients receiving IEC therapy at our institution. METHODS We reviewed clinical characteristics and severity (based on ASTCT Consensus Criteria) in pediatric and AYA patients who received IEC products from 2018–2019 at MDACC. RESULTS Nine patients, median age 15.5 (range: 3–25) years received chimeric antigen receptor (CART) IEC therapy. Four (44%) developed ICANS within median of 8 (range: 3–27) days of CAR T cell infusion and median 6 (range: 2–7) days after CRS. Primary diagnoses were pre-B cell acute lymphoblastic leukemia (8) and mediastinal large B-cell lymphoma (1). Median CRS and ICANS severity grade was 2 (range 1–4). Symptoms included altered mental status (AMS) (5), seizure (1), aphasia (2), impaired ability to write a standard sentence (4). Neuroimaging did not correlate to ICANS symptoms or severity. EEG was performed in 3 and 1 had background slowing correlating with aphasia. CSF was obtained in two revealing lymphocytosis. All received prophylactic anti-epileptic medication and tocilizumab for concomitant CRS. Three received steroids. CONCLUSION ICANS may present in almost half of pediatric patients within one week of receiving CART products associated with CRS. CAR-T trafficking into the CSF may explain pleocytosis in the CSF. Prospective studies may clarify. Impaired ability to write a standard sentence and the Cornell Assessment of Pediatric Delirium (CAPD) may be early indicators of ICANS in pediatric/AYA patients.
TMOD-06. MALIGNANT TRANSFORMATION OF PLEXIFORM NEUROFIBROMAS IN AN NF1 MUTANT MOUSE MODEL OF SPINAL IRRADIATION
Authors: Jean Nakamura, Danny Laurent, Abbi Smith, Waylan Bessler, Wade Clapp, Andrew Horvai
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Understanding the relationships between ionizing radiation (IR) and carcinogenesis, as well as other variables, including genetic background and sex, may minimize risks of transformation from benign to aggressive cancers while maintaining treatment efficacy. We aim to understand the relationship between IR, tumor microenvironments, and effect of sex on malignant transformation using a conditional knockout mouse model of Neurofibromatosis type 1 (NF1). METHODS Conditional knockout mouse models of plexiform neurofibromas (PeriCre+; Nf1fl/fl and PeriCre+; Nf1fl/-, n = 172) were treated with 0 Gy; 3 Gy x 5; 3 Gy x 10 of focal, fractionated spinal irradiation (SI) and aged until signs of illness. Histopathological analysis was performed on images from H&amp;E-stained FFPE peripheral nerve tissues. RESULTS SI affected the survival of mice in a dose-dependent manner, with a significant decrease at 30Gy (median survival 254 and 218 days for 0 Gy and 30 Gy, p &amp;lt; 0.01, Log-rank test). Male mice had reduced overall survival at 15 and 30 Gy (median survival 368, 278 and 245 days for 0, 15 and 30Gy, p &amp;lt; 0.01, Log-rank test), but not in female mice, indicating sex-specific radiosensitivity. Differences in tumour microenvironments did not affect mouse survival after SI. Histopathological analysis is ongoing (43 out of 76 FFPE samples analyzed). Preliminary findings showed a total of 43 malignancies ranging from plexiform neurofibromas (PNs) to high-grade malignant peripheral nerve sheath tumours (MPNSTs). Increasing histologic aggressiveness was observed in higher SI doses, with high-grade MPNST (2.3%) exclusively found in mice irradiated at 30 Gy. CONCLUSION We present a novel mouse model to study malignant transformation in the context of NF1. Preliminary findings suggest increased malignant transformation at high doses of SI.