tbuckley/cabot-search huggingface dataset:
Long-Term Efficacy of Reduced-Intensity Conditioning Compared to Standard Myeloablative Conditioning before Allogeneic Hemopoietic Cell Transplantation in Patients with Acute Myeloid Leukemia in First Complete Remission: 10-Year Follow-up of a Prospective, Open-Label Randomized Phase III Trial
Authors: Frederick Fasslrinner, Johannes Schetelig, Andreas Burchert, Michael Kramer, Rudolf Trenschel, Ute Hegenbart, Michael Stadler, Kerstin Schäfer-Eckart, Michael Bätzel, Hans Eich, Rita Engenhart-Cabillic, Mechthild Krause, Peter Dreger, Andreas Neubauer, Gerhard Ehninger, Dietrich W Beelen, Wolfgang E. Berdel, Timo Siepmann, Matthias Stelljes, Martin Bornhäuser
Journal: Blood (2017)
NCOG-47. CAN YOUNG CHILDREN WITH RELAPSED MEDULLOBLASTOMA BE SALVAGED AFTER INITIAL IRRADIATION-SPARING APPROACHES?
Authors: Craig Erker, Valérie Larouche, Dolly Aguilera, Ashley Margol, Chantel Cacciotti, Sébastien Perreault, Kenneth J Cohen, Mohamed AbdelBaki, Juliette Hukin, Shahrad Rod Rassekh, David D Eisenstat, Beverly Wilson, Anna L Hoppman, Girish Dhall, Taylor Holly, Jeffrey Knipstein, Eric S Sandler, Darren Klawinski, Kathleen Dorris, Taryn B Fay-McClymont, Ralph Salloum, Virginia L Harrod, Bruce Crooks, Vijay Ramaswamy, Jonathan Finlay, Eric Bouffet, Lucie Lafay-Cousin
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Irradiation-sparing approaches are used in young children with medulloblastoma (MB) given the vulnerability of the developing brain to neurocognitive impairment. Limited data are available following relapse for these patients. We aimed to describe the management and outcomes of young children with MB who relapsed after initial treatment without craniospinal irradiation (CSI). METHODS International retrospective study including patients with MB diagnosed between 1995-2017, ≤ 72 months old, initially treated without CSI, who subsequently relapsed. RESULTS Data are available for 66 patients. The median age at initial diagnosis was 27 months (range, 6-72). At diagnosis, 27 patients had metastatic disease. Initial therapy included conventional chemotherapy or with high-dose chemotherapy (HDC) in 30 and 36 patients, respectively. Eight (12.1%) received upfront focal irradiation. Molecular subgrouping was available for 27 (41%) patients. Ten were SHH, five group 3, six group 4 and six others were non-WNT/non-SHH. The median time from initial diagnosis to relapse was 13 months (range, 3-63). Relapse was local, disseminated, or combined in 39%, 32%, and 29%, respectively. The median time to death from relapse was 18 months. Curative intent therapy was given in 53 patients with irradiation (81%), conventional chemotherapy without HDC (40%), and HDC (25%). For patients who received irradiation, 85% received CSI (median dose 33 Gy, 18-41.4) and 15% focal irradiation. Ten patients received chemotherapy without salvage irradiation. The median follow-up time was 44 months (range, 4-255), 33 (62%) patients who underwent curative-intent therapy were alive, including 8/10 SHH, 2/3 group 3, 2/6 group 4, and 4/5 non-WNT/non-SHH. Three of four patients with SHH and treated without salvage radiotherapy are survivors. The 5-year OS for curative intent was 70%. CONCLUSION A substantial proportion of young children who relapse following irradiation-sparing strategies can be salvaged. A proportion of children with SHH MB can be salvaged without salvage radiotherapy.
SURG-37. SYSTEMATIC REVIEW OF GAMMA-KNIFE RADIOSURGERY AND MICROSURGICAL RESECTION FOR BRAINSTEM CAVERNOUS MALFORMATIONS
Authors: Aditya Kondajji, Thien Nguyen, John Sheppard, Daniel Kulinich, Ansley Unterberger, Audree Evans, Kunal Patel, Isaac Yang
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Although microsurgical resection (MR) remains the gold-standard for the treatment of symptomatic cavernous malformations, some authors have proposed the use of radiosurgical Gamma-Knife Surgery (GKS) for lesions that are deep or eloquent, such as those located in the brainstem. OBJECTIVE Here were analyze the literature regarding patient outcomes following MR or GKS for brain stem cavernous malformations. METHODS This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic literature review. A database search of PubMed, Scopus, Embase, and Web of Science was conducted in September 2019. This review included studies evaluating the outcomes of MR or GKS for cavernous malformations located in the brainstem. RESULTS Gross total resection was achieved in the majority of patients and effectively eliminated the risk of recurrent hemorrhage from the operative lesion in studies following the outcomes of MR. GKS reduces the annual hemorrhage rate for patients, although it does not eliminate the cavernous malformation. Both treatment modalities were effective in reducing prior symptomatology. Unlike resection, GKS only reduces the risk of future hemorrhage and does prevent it. CONCLUSIONS Both MR and GKS can improve or stabilize symptoms in patients. However, the therapeutic benefit of GKS may take months to years to take full-effect, resulting in a potential for subsequent hemorrhagic events. MR remains the best treatment option due to its ability to eliminate future bleeding events entirely and should be performed whenever gross total resection is possible.
Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study
Authors: Edgar T Overton, Gary Richmond, Giuliano Rizzardini, Hans Jaeger, Catherine Orrell, Firaya Nagimova, Fritz Bredeek, Miguel García Deltoro, Susan Swindells, Jaime Federico Andrade-Villanueva, Alexander Wong, Marie-Aude Khuong-Josses, Rodica Van Solingen-Ristea, Veerle van Eygen, Herta Crauwels, Susan Ford, Christine Talarico, Paul Benn, Yuanyuan Wang, Krischan J Hudson, Vasiliki Chounta, Amy Cutrell, Parul Patel, Mark Shaefer, David A Margolis, Kimberly Y Smith, Simon Vanveggel, William Spreen
Journal: The Lancet (2020)
MBRS-08. SONIC HEDGEHOG SIGNALING PRIMES CEREBELLAR GRANULE NEURON PROGENITORS, THE CELL OF ORIGIN FOR MEDULLOBLASTOMA, FOR APOPTOSIS BY INDUCING PRO APOPTOTIC BIM
Authors: Abigail Cleveland, Timothy Gershon
Journal: Neuro-Oncology (2020)

Abstract Medulloblastomas, unlike other malignant brain tumors, are typically sensitive to radiation therapy, but the mechanisms that mediate this sensitivity are unclear. Cerebellar granule neuron progenitors (CGNPs), the cell of origin for SHH-subgroup medulloblastoma, are also highly sensitive to radiation. In early life, CGNPs proliferate in response to Sonic Hedgehog (SHH) signaling, and hyperactivation of SHH signaling in CGNPs can lead to the development of SHH-subgroup medulloblastoma. We propose that SHH activation induces radiation sensitivity along with tumorigenesis. We have previously shown that the proapoptotic protein BAX is required for radiation sensitivity of both SHH-driven medulloblastomas and CGNPs in mice, and that BCL-xL supplies critical regulation of BAX, preventing spontaneous cell death. Here, we show that SHH signaling increases the radiation sensitivity of CGNPs by inducing the proapoptotic protein BIM. We found that BIM expression depends on SHH activity, and that genetic deletion of Bim decreases the radiation-sensitivity of CGNPs. Mechanistically, we show that BIM binds to anti-apoptotic proteins BCL-xL and MCL-1, where it may alter the balance of BAX and BCL-xL interactions. Consistent with our mechanistic model, human medulloblastoma patients with high BIM expression show a better prognosis. Based on these observations, we propose that SHH-induced BIM mediates the typical radiation sensitivity of SHH-driven medulloblastoma. Finding ways to enhance BIM activity may open new opportunities for targeted medulloblastoma therapy.
GCT-03. TREATMENT OUTCOMES, PHYSICAL DEVELOPMENT AND QUALITY OF LIFE OF PATIENTS WITH BIFOCAL GERM CELL TUMOURS
Authors: Bo Li
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The optimal radiation field in patients with bifocal germ cell tumours(GCTs) is controversial, especially in non-metastatic cases. Accordingly, we analysed the survival, growth, and health-related quality of life (HRQOL) data of patients with bifocal GCTs. METHODS The data of 87 patients diagnosed with bifocal GCTs at our hospital during the last 10 years were collected. The WHO AnthroPlus software—used to monitor the growth of persons aged 5–19 years—was employed to calculate the Z-score of height (ZSOH) at diagnosis and the last follow-up. The absolute change in the ZSOH was defined as |ZSOH last follow-up - ZSOH diagnosis|. The Pediatric Quality of Life Inventory 4.0 was used to evaluate HRQOL. RESULTS The median follow-up was 49 months (range,6–134 months). Among 49 patients with non-metastatic germinoma, those receiving cranial spinal irradiation(CSI; n=12) or whole-brain radiotherapy (WBRT; n=34) had comparable disease-free survival (DFS;p=0.54), but better DFS than those receiving focal radiotherapy(n=3;p=0.016). Furthermore, among 17 patients with non-metastatic non-germinomatous GCTs, DFS was not significantly different between those treated with CSI(n=4) and those receiving WBRT(n=13;p=0.11). Twenty-nine patients had paired ZSOH data at both diagnosis and the last follow-up. Patients receiving CSI(p=0.026) or &amp;gt;40Gy(p=0.048) experienced a significant decline of absolute change in the ZSOH. HRQOL analysis(n=35) did not reveal difference between patients receiving CSI and those not receiving CSI. CONCLUSIONS Given the comparable DFS and HRQOL but negative impact on growth, CSI could be spared, especially in patients with non-metastatic bifocal germinoma.
IMMU-07. TUMOR STROMA–TARGETING ANTIBODY-CYTOKINE CONJUGATES TO CONVERT THE IMMUNOLOGICALLY COLD GLIOMA MICROENVIRONMENT INTO A HOT ONE
Authors: Tobias Weiss, Emanuele Puca, Manuela Silginer, Teresa Hemmerle, Shila Pazahr, Andrea Bink, Michael Weller, Dario Neri, Patrick Roth
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma is an immunological “desert”. The administration of pro-inflammatory cytokines could shift the balance between tumor-associated immune suppression and anti-tumor immunity but the systemic administration of therapeutically active doses of pro-inflammatory cytokines is hampered by toxic side effects. We investigated different antibody-cytokine fusion products that enable a targeted delivery of interleukin (IL-) 2, IL-12 or tumor-necrosis factor (TNF)α to the tumor site upon systemic administration by binding to a tumor-specific epitope of fibronectin. We confirmed the target antigen expression in ex vivo sections of orthotopic syngeneic glioma mouse models and human glioblastoma samples and characterized the distribution of these antibody-conjugates in glioma-bearing mice upon systemic administration using in vivo imaging. Subsequently, we demonstrated potent anti-tumor activity of these antibody-fusion proteins in fully immunocompetent orthotopic mouse glioma models and characterized their mode of action. We also translated this immunotherapeutic strategy to treat patients with recurrent glioblastoma systemically with an antibody-fusion protein that enables the targeted delivery of TNFα to the tumor site. This was well tolerated, led to a treatment-associated tumor necrosis and increased the number of tumor-infiltrating T cells. This work builds a basis for future studies with antibody-cytokine fusion proteins as a promising treatment strategy for central nervous system tumors.
Effectiveness of adjunctive clindamycin in β-lactam antibiotic-treated patients with invasive β-haemolytic streptococcal infections in US hospitals: a retrospective multicentre cohort study
Authors: Ahmed Babiker, Xiaobai Li, Yi Ling Lai, Jeffrey R Strich, Sarah Warner, Sadia Sarzynski, John P Dekker, Robert L Danner, Sameer S Kadri
Journal: The Lancet Infectious Diseases (2020)
SURG-05. IDEAL TREATMENT REGIMEN FOR PATIENTS WITH ≥1 BRAIN METASTASIS FROM PRIMARY NON-SMALL-CELL LUNG CANCER – A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Authors: Karanbir Brar, Yosef Ellenbogen, Behnam Sadeghirad, Jiawen Deng, Winston Hou, Xiaoqin Wang, Shervin Taslimi, Alireza Mansouri
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). The aim of this study was to assess the comparative effectiveness of treatments for BM from NSCLC. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published until October 2018. We also searched the Chinese databases Wanfang Data, Wanfang Med Online, China National Knowledge Infrastructure, and Chongqing VIP Information for RCTs published until September 2019. Trials including &amp;gt; 10 patients were selected. The primary outcomes were overall survival (OS) and intracranial progression-free survival (PFS). We used a frequentist random-effects model for network meta-analysis and assessed the certainty of evidence using the GRADE approach. RESULTS Among 8798 abstracts, 106 RCTs (9452 patients) met inclusion criteria. Median sample size was 67 (range 25-554). All trials included adult patients with histologically proven NSCLC and &amp;gt;1 BM proven on CT/MRI. Of trials that reported performance status (e.g. ECOG or KPS, n=67), 63/67 excluded patients with non-favorable performance status. Interventions assessed included surgery, WBRT, SRS, targeted therapies (i.e. EGFR/ALK inhibitors), and chemotherapy. Compared to WBRT alone, several interventions demonstrated a statistically significant increase in median OS, including non-targeted chemotherapy + surgery (MD: 415.3 days, 95% CI: 31.3-799.4), WBRT + EGFRi (MD: 200.2 days, 95% CI:146.3-254.1), and EGFRi alone (MD: 169.7 days, 95% CI: 49.7-289.7). Among all interventions, only WBRT + EGFRi showed a significant improvement in median PFS (MD: 108.0 days, 95%CI: 48.5-167.5). CONCLUSIONS Our preliminary analyses indicate an OS and PFS benefit on the addition of EGFR inhibitors to WBRT for the treatment of BMs from NSCLC. Further analyses of hazard ratios for OS/PFS are underway, and subgroup analyses are planned. These data support the growing role of targeted therapies in the treatment of BMs, particularly in susceptible mutant tumours.
Abstract 235: End-Tidal CO2 Monitoring in Non-Intubated Traumatic Brain Injury Patients Receiving O2 via Nasal Cannula vs. Non-Rebreather Mask
Authors: Bruce J Barnhart, Daniel W Spaite, Eric Helfenbein, Saeed Babaeizadeh, Dawn B Jorgenson, Chengcheng Hu, Amber D Rice, Samuel M Keim, Octavio Perez
Journal: Circulation (2018)

Background: The advent of highly sensitive End-Tidal CO2 (ETCO2) sensors allows effective monitoring of intubated patients in many emergency care settings, including EMS. Previous work has explored the use of ETCO2 monitoring in non-intubated patients with sensors placed in the nares. However, nothing is known about the effect of passive oxygen delivery [nasal cannula (NC) or non-rebreather mask (NRB)] on ETCO2 measurement. Objective: To compare ETCO2 measurements in non-intubated Traumatic Brain Injury (TBI) patients receiving O2 via NC vs NRB in the prehospital setting. Methods: A subset of major TBI cases (CDC Barell Matrix Type-1) in the Excellence in Prehospital Injury Care (EPIC) TBI Study (NIH/NINDS-1R01NS071049; ClinicalTrials.gov-NCT01339702) were evaluated 4/13-3/17). Non-intubated cases from 6 EMS agencies providing monitor data (Philips MRx) were included when continuous ETCO2 data were available. Statistics: Two-tailed t test, α = 0.05. Results: The 104 included cases had median age of 50.5 (range: 9-91; male: 67%). 39 (37.5%) received O2 via NC and 65 (62.5%) via NRB. Mean ETCO2: NC cases: 27.7 mmHg (95% CI: 25.7, 29.8); NRB: 30.0 (28.1, 31.8; p=0.132). There were also no significant differences among the mean lowest recorded values (p=0.449) or the mean highest values (p=0.275). Conclusion: We believe this is the first report comparing ETCO2 values based upon the method of passive O2 delivery in non-intubated patients. The minor differences between NC vs NRB-oxygenated patients was neither statistically nor clinically significant. This is surprising since: 1) the O2 flow rates and 2) the open-air (NC) vs mask (NRB) delivery methods are so dramatically different. Future study is needed to identify the clinical implications of using noninvasive ETCO2 measurement as a tool for monitoring ventilatory status and changes in non-intubated TBI (and other) patients.
The role of aspirin desensitization followed by oral aspirin therapy in managing patients with aspirin-exacerbated respiratory disease: A Work Group Report from the Rhinitis, Rhinosinusitis and Ocular Allergy Committee of the American Academy of Allergy, Asthma &amp; Immunology
Authors: Whitney W. Stevens, Elina Jerschow, Alan P. Baptist, Larry Borish, John V. Bosso, Kathleen M. Buchheit, Katherine N. Cahill, Paloma Campo, Seong H. Cho, Anjeni Keswani, Joshua M. Levy, Anil Nanda, Tanya M. Laidlaw, Andrew A. White
Journal: Journal of Allergy and Clinical Immunology (2020)
HGG-49. A PEDIATRIC THALAMIC HIGH-GRADE GLIOMA WITH <i>H3F3A</i> K27M AND <i>BRAF</i> V600E DOUBLE MUTATIONS
Authors: Keita Terashima, Masahiro Sugawa, Kenichi Sakamoto, Chikako Kiyotani, Tomoo Osumi, Yoko Shioda, Takao Deguchi, Motohiro Kato, Daisuke Tomizawa, Kenichi Usami, Hideki Ogiwara, Yoshiyuki Tsutsumi, Hiroshi Fuji, Noriyuki Nakano, Takako Yoshioka, Yoshiko Nakano, Koichi Ichimura, Kimikazu Matsumoto
Journal: Neuro-Oncology (2020)

Abstract CASE A 18-month-old boy presented with approximately 2 months history of progressive left hemiparesis and left exotropia. MRI study showed a 3–4 cm T1-iso, T2-high tumor at right thalamus to midbrain with little contrast enhancement. The patient underwent endoscopic biopsy of the tumor, which showed relatively dense proliferation of small cells with round nuclei, mitosis of the tumor cell, but no necrosis. Immunohistochemical showed positive stain of GFAP and Olig2. Ki-67 was 34%. The histopathological diagnosis was compatible with high grade glioma. Chemotherapy with vincristine, cyclophosphamide, cisplatin and etoposide was initiated. Molecular testing of the tumor revealed H3F3A K27M and BRAF V600E double mutations in DNA from frozen tumor tissue. DISCUSSION The concurrent mutation of H3F3A K27M and BRAF V600E in pediatric glioma is very rare, but there are several cases previously reported in literature. Interestingly those cases are heterogenous in age, location, histopathological subtypes and clinical outcome.
RARE-11. QUANTITATIVE MR IMAGING FEATURES ASSOCIATED WITH UNIQUE TRANSCRIPTIONAL CHARACTERISTICS IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA: A POTENTIAL GUIDE FOR THERAPY
Authors: David Mirsky, Eric Prince, Susan Staulcup, Astrid Hengartner, Trinka Vijmasi, James Johnston, Luca Massimi, Richard Anderson, Mark Souweidane, Robert Naftel, David Limbrick, Gerald Grant, Toba Niazi, Roy Dudley, Lindsay Kilburn, Eric Jackson, George Jallo, Kevin Ginn, Amy Smith, Joshua Chern, Amy Lee, Annie Drapeau, Mark Krieger, Michael Handler, Todd Hankinson
Journal: Neuro-Oncology (2020)

Abstract METHODS Through the Advancing Treatment for Pediatric Craniopharyngioma (ATPC) consortium we accumulated preoperative MRIs and tumor RNA for 50 unique ACP patients. MRIs were assessed quantitatively for 28 different features and analyzed using Multiple Factor Analysis (MFA) and optimal clustering was determined via maximization of Bayesian Information Criterion (BIC). Following bulk RNAseq, differential expression and pathway enrichment were performed using standard methodologies (i.e., DESeq2 and GSEA). RESULTS MRI features were well represented in the first 3 dimensions of MFA (variance explained=67.32%); specifically tumor/cyst size, ventricular size, and cyst fluid diffusivity. Using this three-way axis, we identified 3 patient subgroups. Transcriptional differences between these subgroups indicated one group was enriched for DNA damage response and MYC related pathways, one group enriched for SHH, and one group enriched for WNT/β-catenin and EMT-related pathways. CONCLUSION This preliminary work suggests that there may be unique gene expression variants within ACP, which may be identified preoperatively using easily quantifiable MRI parameters. These radiogenomic signatures could provide prognostic information and/or guidance in the selection of antitumor therapies for children with ACP.
63MO TG4001 therapeutic vaccination combined with PD-L1 blocker avelumab remodels the tumor microenvironement (TME) and drives antitumor responses in human papillomavirus (HPV)+ malignancies
Authors: C. Le Tourneau, P. Cassier, F. Rolland, S. Salas, J-M. Limacher, O. Capitain, O. Lantz, A. Lalanne, C. Ekwegbara, A. Tavernaro, H. Makhloufi, K. Bendjama, J-P. Delord
Journal: Annals of Oncology (2020)
DDEL-12. NANOPARTICLE DELIVERY OF DOXORUBICIN FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
Authors: Caitlin Ung, Maria Tsoli, Jie Liu, Domenico Cassano, Dannielle Upton, Anahid Ehteda, Friederike Mansfield, Tim Failes, Maria Kavallaris, Greg Arndt, Orazio Vittorio, Valerio Voliani, Giuseppe Cirilo, David S Ziegler
Journal: Neuro-Oncology (2020)

Abstract DIPGs are the most aggressive pediatric brain tumors. Currently, the only treatment is irradiation but due to its palliative nature patients die within 12 months. Effective delivery of chemotherapy across the blood-brain barrier (BBB) has been a key challenge for the eradication of this disease. We have developed a novel gold nanoparticle functionalised with human serum albumin (Au-NP, 98.8 ±19 nm) for the delivery of doxorubicin. In this study, we evaluated the cytotoxic efficacy of doxorubicin delivered through gold nanoparticles (Au-NP-Dox). We found that DIPG neurospheres were equally sensitive to doxorubicin and Au-NP-Dox (at equimolar concentration) by alamar blue assay. Colony formation assays demonstrated a significantly more potent effect of Au-NP-Dox compared to doxorubicin alone, while the Au-NP had no effect. Furthermore, western blot analysis indicated increased apoptotic markers cleaved Parp, caspase 3/7 and phosphorylated H2AX in Au-NP-Dox treated DIPG neurospheres. Live cell content and confocal imaging demonstrated significantly higher uptake of Au-NP-Dox compared to doxorubicin alone. Treatment of a DIPG orthotopic mouse model with Au-NP-Dox showed no signs of toxicity with stable weights being maintained during treatment. However, in contrast to the above in vitro findings the in vivo study showed no anti-tumor effect possibly due to poor penetration of Au-NP-Dox into the brain. We are currently evaluating whether efficacy can be improved using measures to open the BBB transiently. This study highlights the need for rigorous in vivo testing of new treatment strategies before clinical translation to reduce the risk of administration of ineffective treatments.