tbuckley/cabot-search huggingface dataset:
NIMG-05. ADVANCED IMAGING TO ASSESS LONGITUDINAL VASCULAR CHANGES IN BRAIN METASTASES TREATED WITH CHECKPOINT INHIBITION
Authors: Albert Kim, Jonathan Cardona, Ken Chang, Andrew Beers, James Brown, Kyrre Emblem, Jayashree Kalpathy-Cramer, Eudocia Lee, Nancy Lin, Sara Tolaney, Lakshmi Nayak, Ugonma Chukwueke, Kevin Oh, Helen Shih, Michael White, Donald Lawrence, Beverly Moy, Justine Cohen, Anita Giobbie-Hurder, Daniel Cahill, Ryan Sullivan, Priscilla Brastianos, Elizabeth Gerstner
Journal: Neuro-Oncology (2020)

Abstract Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) in melanoma and lung cancer. However, accurately assessing intracranial response in patients undergoing ICI is a challenge, as current measures cannot reliably distinguish pseudoprogression from true tumor progression. To identify potential biomarkers of response, we analyzed standard post-contrast and dynamic susceptibility contrast MRI to identify characteristic vascular signatures as part of an ongoing Phase 2 study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology. Tumor volume measurements were calculated by summating all enhancing voxels. A volumetric increase of &amp;gt;40% was categorized as progressive disease (PD), a decrease of &amp;gt;60% as partial response (PR), and stable disease (SD) as between -60% and +40%. 78 patients have been enrolled, of whom 44 have received at least baseline advanced MR imaging. Histologies include 21 with breast cancer, 5 with non-small cell lung cancer, 4 with melanoma, and 13 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 33 evaluable patients include 4 PR, 10 SD, and 19 PD. On preliminary analysis, there was a correlation between increased tumor cerebral blood volume/flow with tumor progression. Correlation of additional vascular physiologic parameters (e.g. vessel caliber, tissue oxygenation) to volumetric response, patient outcome, and standardized response criteria (iRANO) are ongoing. Our data provides potential evidence that effective ICI is associated with a decrease in perfusion. Ongoing analyses to uncover additional vascular changes – specifically longitudinal metrics reflecting vascular structure and function - within BM to ICI are pending. These findings have potential to explore mechanisms of ICI response and resistance, as well as biomarkers of response.
Extracellular vesicle microRNAs as predictors of response to omalizumab in chronic spontaneous urticaria
Authors: Taha Al‐Shaikhly, James W. MacDonald, Theo K. Bammler, Matthew C. Altman, Andrew G. Ayars, Daniel H. Petroni, Stephen A. Tilles, William R. Henderson
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract 14095: Outcomes of Pulmonary Arterial Hypertension are Improved in a Specialty Care Center
Authors: Hongyang Pi, Chad Kosanovich, Adam Handen, Michael Tao, Jacqueline Visina, Gabrielle Vanspeybroek, Mehdi Nouraie, Stephen Y Chan
Journal: Circulation (2019)

Introduction: Pulmonary arterial hypertension (PAH) is characterized by progressive elevation of pulmonary arterial pressures typically managed by targeted vasodilator therapies. Current guidelines...
Subcutaneous Compared to Intravenous Administration of Rituximab Plus CHOP in Patients with Diffuse Large B-Cell Lymphoma — a Study By the Polish Lymphoma Research Group
Authors: Ewa Paszkiewicz-Kozik, Monika Dlugosz-Danecka, Paweł J. Robak, Elżbieta Wojciechowska-Lampka, Monika Swierkowska-Czeneszew, Joanna Tajer, Joanna Romejko-Jarosinska, Katarzyna Domanska-Czyz, Marcin Szymanski, Marta Morawska, Lukasz Targonski, Michal Osowiecki, Beata Ostrowska, Anna Paulina Dabrowska-Iwanicka, Jan Walewski
Journal: Blood (2017)
NIMG-55. A QUANTITATIVE ANALYSIS OF BRAIN VOLUME DYNAMICS IN PCNSL PATIENTS TREATED WITH HIGH-DOSE METHOTREXATE-BASED THERAPY
Authors: Ananyaa Sivakumar, David Kamson, Fayez Estephan, Sebastian Lambrecht, Omar Dzaye, Nina Wagner-Johnston, Lode Swinnen, Douglas Gladstone, Doris Lin, Stuart Grossman, Matthias Holdhoff
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Primary CNS lymphoma (PCNSL) is a rare, infiltrative disease. High-dose methotrexate (HD-MTX) is the backbone of induction regimens for PCNSL. While MTX-associated white matter changes are well-described, treatment-related brain volume loss is much less understood, especially in radiotherapy-naïve cohorts. Here, we aimed to longitudinally quantify the rates of brain volume loss in PCNSL patients treated with HD-MTX. SUBJECTS/METHODS We included 12 radiotherapy-naïve patients (age mean±SD 61±15y, range 37-84y, 9F) with histopathologically confirmed PCNSL who received HD-MTX induction (mean±SD 12±4 cycles, range 8-18) +/-rituximab. MRIs were collected from within 1 month of HD-MTX initiation until the end of follow-up (mean±SD: 3.7±2.9y). Longitudinal whole-brain segmentation was performed on FLAIR images using the Sequence Adaptive Multimodal Segmentation tool of FreeSurfer. Brain volumes were normalized to the initial scan, white matter lesion volumes were normalized to cerebral volume (nWML). RESULTS The average rate of cerebral volume change was -2.1±1.9%/year. Half of patients showed marked cerebral volume loss in the first year (-5.6±1.4% vs. -2.0±1.4%; n=10; p=0.003) with the most prominent change occurring within 6-months of treatment initiation (-4.2±1.7% vs. -0.5±1.6; n=12; p=0.004). Cerebral volume loss reached a plateau after the 1-year mark in both groups (0.3±0.8%/year vs. 1.4±3.3%/year; n=8; p=0.4). Patients younger than 61 years exhibited markedly higher rates of cerebral volume loss (-6.2±1.1%/year vs. 2.4±1.5%/year p=0.003), which was corroborated by strong inverse correlation between age and cerebral volume loss (Pearson’s r=-0.82, p=0.004). Neither the cerebellar volume, nor the nWML load correlated with age. CONCLUSION In the present cohort, brain volume loss was approximately four-fold higher than what is described in the healthy aging. Younger patients treated with HD-MTX exhibited more severe cerebral volume loss, which may be due to higher initial brain volume reserve. Detailed analyses of a larger sample are underway.
A Vessel for Change: Endothelial Dysfunction in Cerebral Small Vessel Disease
Authors: Sophie Quick, Jonathan Moss, Rikesh M. Rajani, Anna Williams
Journal: Trends in Neurosciences (2020)

The blood vessels of the brain are lined with endothelial cells and it has been long known that these help to regulate blood flow to the brain. However, there is increasing evidence that these cells also interact with the surrounding brain tissue. These interactions change when the endothelial cells become dysfunctional and have an impact in diseases such as cerebral small vessel disease, the leading cause of vascular dementia. In this review, we focus on what endothelial dysfunction is, what causes it, how it leads to surrounding brain pathology, how researchers can investigate it with current models, and where this might lead in the future for dementia therapies.
Response to Dr. Frieling
Authors: Shanshan Shen, Hui Luo, Qiang Cai
Journal: Endoscopy (2020)

See also:Gastric peroral endoscopic pyloromyotomy versus gastric electrical stimulation in the treatment of refractory gastroparesis: a propensity score-matched analysis of long term outcomesEndoscopy 2020; 52(05): 349-358DOI: 10.1055/a-1111-8566See also:Gastroparesis – too complicated for a simplistic therapeutic approachEndoscopy 2021; 53(01): 98-98DOI: 10.1055/a-1194-4717
NCOG-19. BEVACIZUMAB IN REAL LIFE PATIENTS WITH RECURRENT GLIOBLASTOMA: BENEFIT OR FUTILITY?
Authors: Cristina Smolenschi, Emeline Colomba, Elie Rassy, Naima Lezghed, Mohamed Kettab, Guillaume Louvel, Gabriel Garcia, Bianca Cheaib, Sophie Bockel, Johan Pallud, Edouard Dezamis, Razvan Copaciu, Steven Knafo, Samy Ammari, Frederic Dhermain, Julien Domont, Larisa Martanovschi, Fekih Mahmoud, Sarah Dumont
Journal: Neuro-Oncology (2020)

Abstract Angiogenesis represents a hallmark of glioblastoma but most trials disappointed and failed to change the poor outcome of this disease. However, Bevacizumab (Bev) is widely used in clinical practice by expert oncologists due to experience or efficacy in real life.We retrospectively reviewed the use of Bev and its benefit in terms of Time to treatment failure (TTF), Overall Survival(OS), Objective Response Rate (ORR) and clinical benefit. METHODS: We analyzed two hundred and two patients treated at Gustave Roussy Cancer Campus with Bev until definitive failure for recurrent glioblastoma between 2006 and 2016. Patients were treated with Bev alone or in association with radiotherapy, temozolomide, lomustine or irinotecan. RESULTS: The median duration of Bev treatment until definitive failure was 6 months. The median TTF was 7.27 months(95%CI 6.30-8.24) and the median OS from diagnosis was 22.43 months(95%CI 19.68-25.18). Two patients were still alive without active treatment at the end of study. A hundred and fourteen (56%) patients experienced symptom amelioration and seventy-five (37%) improved their Performance Status. Fifty percent of patients exhibited Partial and Complete Response on MRI, as best radiological response, within 1.6 months. No patient had anaphylactic reaction. Grade 1-2 hypertension(HT)(17%) and grade 1(10%) proteinuria were most common. Six patients presented lethal toxicity: 4 with GI perforation, 1 p with cerebral hemorrhage and 1 p with arterial bleeding. HT was correlated with treatment response in 67% of patients. A neutrophil count superior to 6000/mm³ was associated with longer TTF(mTTF 8.23m(95%CI 6.64-9.82). CONCLUSION: This retrospective study reports a substantial clinical benefit of Bev in patients with recurrent glioblastoma with an acceptable toxicity profile. As the panel of therapeutic option is still very limited in these tumors, this work supports the maintained use of Bev as a therapeutic option.
BIOM-44. GENOMIC PREDICTORS OF ADVERSE EVENTS IN NEWLY DIAGNOSED IDH-WILDTYPE GLIOBLASTOMA
Authors: Mary Jane Lim-Fat, Rifaquat Rahman, Alona Muzikansky, Eleanor Woodward, Sydney Whorral, Marie Allen, Mehdi Touat, Bryan Iorgulescu, Gilbert Youssef, Ugonma Chukwueke, Jose Mcfaline-Figueroa, Lakshmi Nayak, Eudocia Lee, David Reardon, Raymond Huang, Rameen Beroukhim, Wenya Linda Bi, Keith Ligon, Patrick Wen
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Adverse outcomes including lymphopenia, thromboembolism (VTE), pseudoprogression and seizures cause significant morbidity in glioblastoma (GBM) patients. The association between genomic biomarkers and adverse outcomes in IDH-wildtype (IDH-wt) GBM needs to be further validated. METHODS We identified 1,011 consecutive adult patients with histologically confirmed GBM with OncoPanel testing (capture-based next-generation sequencing of 447 cancer-associated genes) at Dana-Farber Cancer Institute from 2013–2019. IDH-mutant patients and those without consistent follow-up at DFCI were excluded. Seizure at presentation, lymphopenia (absolute lymphocyte count &amp;lt; 1.0x109/L) at the beginning and end of chemoradiation, VTE, radiographic pseudoprogression (&amp;lt; 6 months of RT end) and early progression (&amp;lt; 6 months since completing RT) were identified retrospectively as adverse events. Single nucleotide variants and indels of relevant genes (Tier 1 or 2 mutations) and copy number analysis were derived. Variables were compared using Wilcoxon rank-sum test or Fisher’s Exact test with p&amp;lt; 0.05 indicating statistical significance. RESULTS Among 557 patients included, 198/508 (39%) had MGMT-methylated GBMs. Seizure at presentation occurred in 176/542 (32%) and was more common in TP53- or RB1-mutant GBM. Pre-RT 83/338 (25%), but not post-RT lymphopenia (249/367, 68%), was associated with PIK3CA mutation. VTE was detected in 74/509 (15%) during follow-up and was associated with mutations in PIK3CA and POLE. Pseudoprogression was noted in 43/457 (9%) of patients and was not associated with MGMT status or genomic alterations. Early progressive disease occurred in 33% of patients and was associated with unmethylated MGMT, PIK3CA, STAG2 and PTPN11 mutations. Median overall survival for the entire cohort was 17.5 months. CONCLUSION PIK3CA mutations were associated with baseline lymphopenia, risk of VTE and early progression in this cohort. Genomic biomarkers may help identify patients at higher risk of select adverse events in IDH-wt GBM. This could benefit patients through tailoring of supportive care and prophylactic therapies.
DIPG-83. USING COPPER CHELATING AGENTS TO TARGET RECEPTOR TYROSINE KINASE SIGNALLING IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
Authors: Filip Michniewicz, Federica Saletta, Jourdin Rouen, David Ziegler, Orazio Vittorio
Journal: Neuro-Oncology (2020)

Abstract DIPG is a universally fatal pediatric brain cancer. Receptor tyrosine kinase (RTK) pathway alterations are among the defining characteristics in many patients. Copper is a transition metal essential for cellular signaling, known to impact PI3K/AKT and MAPK/ERK pathways. Copper chelating agents are clinically approved for use in children with Wilson’s Disease, documented to reduce brain copper levels and are cited as potential cancer therapeutics. Due to copper’s wide cellular integration, we propose that targeting copper in DIPG through use of copper chelators is a viable therapeutic strategy and are strong candidates for combination therapy. Cytotoxicity assays performed in a panel of DIPG cell lines using copper chelator tetraethylenepentamine (TEPA) demonstrated a millimolar range of efficacy. To identify copper integrated pathways, western blots were performed on DIPG cell lines dosed with sub-lethal copper concentrations, which increased phosphorylated expression of AKT, ERK1/2, ERK5 and STAT3. Conversely, western blots performed after TEPA treatment demonstrated reduced phosphorylated expression of all these proteins compared to controls. Western blots investigating TEPA in combination with Everolimus and Trametinib demonstrated synergistic targeting of these proteins. Our results indicate that adding copper in the culture media initiated two RTK-mediated downstream signal transductions, including AKT and ERK and additionally STAT signaling. The use of copper chelator TEPA affected copper homeostasis and reduced DIPG cell proliferation. Our study proposes copper plays an important role in RTK-mediated signaling promoting DIPG proliferation. This implies that reducing copper with clinically available chelation agents can represent a potential anti-cancer treatment for DIPG.
Allocating Resources Across the Life Span During COVID-19—Integrating Neonates and Children Into Crisis Standards of Care Protocols
Authors: Monica E. Lemmon, Robert D. Truog, Peter A. Ubel
Journal: JAMA Pediatrics (2020)

This Viewpoint discusses the need to account for neonates and children—who are typically disproportionally impacted during pandemics—by implementing hospital resource allocation protocols that ensure equity across the life span.
Factoring in ANGPTL3 When LDL Is Refractory
Authors: Seth S. Martin
Journal: New England Journal of Medicine (2020)

Patients with familial hypercholesterolemia, who have a severely increased low-density lipoprotein (LDL) cholesterol level from birth and are at high risk for premature cardiovascular disease, have inspired and contributed to major advances in lipid therapeutics. A notable example is the drug class targeting proprotein convertase subtilisin–kexin type 9 (PCSK9). Overactivity of PCSK9, which promotes LDL receptor degradation, was discovered to be a cause of familial hypercholesterolemia.1 The addition of a PCSK9 inhibitor to statin therapy can lower the LDL cholesterol level by 60% and reduce cardiovascular risk.2 Reduction of cardiovascular risk with PCSK9 inhibitors is correlated with absolute lowering of . . .
GCT-29. DOES TUMOUR MARKER DECLINE PREDICT OUTCOME IN INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOURS (NGGCTs)?
Authors: Cecile Faure Conter, Audrey Lardy-Cleaud, Matthew Murray, James Nicholson, Lea Guerrini-Rousseau, Gilles Palenzuela, Claire Alapetite, Maria Louise Garre, Rolf Kortmann, Frank Saran, Thankamma Ajithkumar, Torsten Pietsch, Alexandre Vasiljevic, Umberto Ricardi, Beate Timmermann, Jans Enno Muller, Gabriele Calaminus
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION The prognostic impact of tumour marker (TM) decline rate has been demonstrated for extracranial poor prognostic non-seminomatous/germinomatous germ cell tumours (NGGCT). The current series aimed to assess if this finding can be applied to intracranial primaries. METHODS Patients were retrieved from the SIOP-CNS-GCT-96 database. They were selected if they had i/assessable values of serum alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG) before and 18 to 28 days after the first course of chemotherapy and ii/ available data for outcome. Decline rate was calculated using a logarithmic transformation and expressed as time to normalization (TTN) as published by Fizazi (JCO 2004). TTN≤ 9 weeks for AFP and ≤ 6 weeks for HCG were considered as favourable decline rate. Prognostic impact of TTN on outcomes was assessed using the log-rank test. RESULTS Out of 149 patients with NGGCT, 59 were evaluable for both HCG and AFP TTN of whom 44 (74%) had a favourable decline rate. After a median follow-up of 88 months (2–251), 20 relapses and 15 deaths occurred. The 5-year PFS rates were 72% and 60% in patients who had a favourable and an unfavourable TTN, respectively (p=0.15). The 5-year OS rates were 77 % and 69%, respectively (p=0.66). Separate analysis of TTN based only on AFP or only on HCG gave similar results. CONCLUSION Despite the use of a methodology similar to that used in extracranial NGGCT, no significant impact of serum TM decline on prognosis was observed, but insufficient statistical power cannot be ruled out.
EPEN-50. THE MANAGEMENT AND TREATMENT OF PEDIATRIC SPINAL CORD EPENDYMOMA: RESULTS FROM A COLLABORATIVE INTERNATIONAL MULTI-INSTITUTIONAL REVIEW
Authors: John Lucas, Ella Kumirova, Derek Tsang, Anna Vinitsky, Jason Chiang, Lili-Naz Hazrati, Shelby Lane, Harold Agbahiwe, Santhosh Upadhyay, Christopher Tinkle, Dmitry Konovalov, Moatasem El-Ayadi, Eslam Maher, Victoria Emtsova, Alexey Nechesnyuk, Nasim Sarhan, Anna Loginova, Chih-Yang Hsu, Matthew Ladra, Stephanie Terezakis, Frederick Boop, Paul Klimo, Soha Ahmed, Normand Laperriere, Vijay Ramaswamy, Thomas Merchant
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Pediatric Spinal cord ependymoma (SCE) is rare, and the management is often heterogeneous across centers. We evaluated the impact of clinical, pathologic, and treatment-related factors on outcomes in a multi-institutional, international cohort. METHODS SCE patients age &amp;lt;21 years were reviewed across 5 institutions. We utilized nonparametric descriptive statistics, survival, and recursive partitioning analysis (RPA) to examine patient, tumor, histopathologic and treatment characteristics, failure pattern, and cause of death. RESULTS 125 patients were identified, 18 (14.4%) with metastases. Initial surgery was GTR, and STR in 44, 56% of patients respectively. Histology was grade 1, 2, and 3 in 55, 17.7 and 23.2% respectively. 55 patients with initial GTR were observed (52.7%) or irradiated (43.6%); 60 patients had STR and were observed (40%) or irradiated (60%). The 7-year event-free (EFS) and overall survival (OS) was 60% (95% CI 51.5–71.4) and 79% (95% CI 71.1–87.8) respectively. STR and metastasis increased the hazard for death [HR 1.87, 95% CI 1.02–3.57, p=0.05 (vs. GTR)] and [HR 2.28, 95% CI 1.1–5.2, p=0.048 (vs. localized)] respectively. Across 43 failures, local failure predominated (48.8%). Distant and combined failure occurred in 30.2 and 13.9% respectively. Adjuvant RT offered a 20% absolute improvement (vs. observation) in EFS at 5 years regardless of extent of resection. RPA identified thoracic (vs. non-thoracic), grade (1 &amp; 3 vs. 2), STR (vs. GTR) and metastases as determinants of inferior EFS. CONCLUSIONS Tumor and treatment-related factors are predictive of EFS. OS is favorable despite diverse schema and frequent distant failures.
NCMP-08. EFFICACY OF ANTIEPILEPTIC DRUGS IN GLIOMA PATIENTS WITH EPILEPSY: A SYSTEMATIC REVIEW
Authors: Marjolein de Bruin, Pim van der Meer, Linda Dirven, Martin Taphoorn, Johan Koekkoek
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Epilepsy is a common symptom in glioma patients, requiring antiepileptic drug (AED) treatment. However, comprehensive data on the efficacy and tolerability of AED treatment is currently lacking. In this systematic review we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma. METHODS Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane library were searched up to April 2020. Three different outcomes were extracted from all eligible articles: (I) seizure freedom; (II) ≥50% reduction in seizure frequency; and (III) treatment failure. To overcome variation with respect to sample sizes, weighted averages (WA) were calculated for outcomes at 6 and 12 months. RESULT A total of 64 studies were included. For monotherapy, the 6-months seizure freedom rate was highest for phenytoin (WA=72%), whereas the 12-months seizure freedom rate was highest for pregabalin (WA=75%). For achieving ≥ 50% seizure reduction, levetiracetam was the most effective AED at 6 and 12 months, with WA of 82 and 97% respectively. Considering the provided polytherapy combinations, levetiracetam combined with phenytoin was most effective followed by levetiracetam with valproic acid. Seizure freedom rates with polytherapy at 6 months and 12 months were highest for combinations with phenytoin and topiramate, respectively. For achieving a ≥ 50% seizure reduction, combinations with perampanel were found to be the most effective at 6 and 12 months. CONCLUSION Based on the current literature, phenytoin, levetiracetam and pregabalin are most effective as AED monotherapy in glioma patients with epilepsy. Well-controlled prospective studies are needed to help further guide clinician’s treatment choices.