tbuckley/cabot-search huggingface dataset:
MBRS-61. MOLECULAR SUB-GROUPING OF PEDIATRIC MEDULLOBLASTOMA: CORRELATION WITH CLINICAL AND HISTOLOGICAL FEATURES, A SINGLE INSTITUTIONAL STUDY
Authors: Gauri Deshpande, Mamta Gurav, Omshree Shetty, Vinayak Kadam, Vishal Chaubey, Tejpal Gupta, Aliasgar Moiyadi, Girish Chinnaswamy, Sridhar Epari
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Molecular subgroups of pediatric medulloblastomas are distinctive in infantile and non-infantile age-groups. METHODS Real-time quantitative PCR based GEP of customized 12 protein-coding genes was performed on 206 FFPE childhood medulloblastoma samples. FISH for MYC amplification, monosomy 6 and sequencing for CTNNB1 exon 3 mutation were done in relevant cases. H&amp;E and reticulin-stained slides were used for histological subtyping. p53-protein immunoreactivity pattern was noted. RESULTS Infantile (n=33) comprised 57.6% SHH-activated (desmoplastic: 73.7%; MBEN: 15.8% and classic: 10.5%), 21.2% group 3 (large cell/anaplastic [LCA]: 28.6% and none were desmoplastic) and 12% group 4. 40% of group 3 patients died of disease and 21% of the SHH-activated (all desmoplastic) had subsequent local recurrence. Non-infantile (n=173) comprised 19.4% WNT-activated, 12.9% SHH-activated (15% classic, 30% desmoplastic, 10% paucinodular), 19.4% group 3 (63.3% classic &amp; 26.7% LCA), 48.4% group 4 (73.3% classic, 5.3% desmoplastic, 10.7% paucinodular &amp; 1.4% LCA), and non-WNT/non-SHH (NWNS), NOS (n=14,9%) and unclassified (n=4,2.6%). None of WNT-activated were desmoplastic/LCA histology. Non-infantile WNT-activated and group 3 MBs showed 90% monosomy 6 &amp; CTNNB1 mutation, and 16.7% MYC-amplification respectively. 17.4% (13% spinal, 4.4% local) WNT-activated, 31% (12.5% local, 18.5% distant [spinal: 12.5%, intracranial:6%]) SHH-activated, 27% (18% both spinal and local, 9% spinal) group 3 and 31.5% (7.4% local, 5.5% intracranial, 11.2% spinal, 7.4% both spinal and local) group 4 showed metastases during follow up. CONCLUSIONS SHH-activated and group 3 are the common infantile subgroups but group 4 is not non-existent in infantile age. No desmoplastic (including paucinodular) histological subtype is of WNT- activated and group 3.
Abstract 15938: Safety of Radiofrequency Ablation Without Pre-Procedural Trans-Esophageal Echocardiography in Patients With Atrial Fibrillation on Novel Oral Anticoagulants
Authors: Mohamed Diab, Oussama M Wazni, Khaldoun Tarakji, Walid I Saliba, Mohamed H Kanj, Daniel J Cantillon, John Rickard, Niraj Varma, Bruce L Wilkoff, Thomas Callahan, David O Martin, Mark J Niebauer, Thomas J Dresing, Bruce D Lindsay, Mina K Chung, Ayman Hussein
Journal: Circulation (2019)

Introduction: Many centers continue to routinely perform trans-esophageal echocardiograms (TEE) prior to atrial fibrillation (AF) ablation procedures in patients treated with direct oral anticoagul...
DDRE-14. HEMP DERIVED EXTRACELLULAR VESICLES (EVS): A POTENTIAL ANTI-GLIOMA THERAPY
Authors: Hassan Azari, Nasser Nassiri Koopaei, Mohammad-Zaman Nouri, Jesse D Hall, Nancy D Denslow, Thomas D Schmittgen, Brent A Reynolds
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Extracellular vesicles (EVs) have been harvested from many plant sources, some of which have anti-cancer effects and some could be used as therapeutic nanodelivery vectors. Hemp plant is a natural source of cannabinoids, of which delta 9-tetrahydroxicannabinol (THC) and cannabidiol (CBD) have proven anti-cancer proprieties. HYPOTHESIS We hypothesized that hemp EVs are enriched in cannabinoids and their application will reduce glioblastoma (GBM) tumor progression. APPROACH EVs were isolated from the hemp plant using ultracentrifugation. Nanotracking analysis, electron microscopy and liquid chromatography tandem mass spectrometry (LC-MS/MS) were utilized to characterize EVs. GBM cell lines were cultured in the neuropshere assay to evaluate hemp EVs anti-glioma effects. Fluorescent-labelled EVs were used to evaluate their brain tissue distribution in orthotopic patient-derived GBM xenografts. RESULTS Hemp EVs have a median diameter of 112.6nm with a typical lipid-bilayer structure. LC-MS/MS have shown that while cannabidiolic, cannabigerolic, and tetrahydroxicannabinolic acids represent 69.1 ± 2.1%, 19.1 ± 1.6%, 6.5 ± 0.54% of the total cannabinoids in hemp EVs, CBD and THC only make 4.75 ± 0.26%, and 0.5 ± 0.3%. Hemp EVs are potent anti-glioma agents with a 7-day LD-50 of 1.04µM and 2.4µM [based on EVs total cannabinoid content] for KR-158 and L0 GBM lines, respectively. Compared to the vehicle, overnight incubation of L0 cells with 1µM hemp EVs significantly reduced GBM cell migration (630.3 ± 61.43 vs 143.7 ± 8.7). Intranasal administration of hemp EVs led to a widespread distribution in tumor bearing brain including GBM tumor core. CONCLUSION Based on these results, hemp EVs with enriched cannabinoid content exert antiglioma effect in-vitro and when delivered intranasally, are widely distributed throughout the brain and within the tumor of PDX animals. Further experiments are ongoing to address the impact of nasally-delivered hemp EVs on tumor progression and compare to the application of purified acidic cannabinoids.
Abstract 10009: Circulating Pcsk9 Levels Are Not Associated With the Conversion to Type 2 Diabetes
Authors: Stephane Ramin-Mangata, Gilles Lambert
Journal: Circulation (2019)

Introduction: Despite their beneficial effects in lowering LDL-cholesterol and CVD risk, statins slightly but significantly increase the risk of new-onset diabetes (NOD). Mendelian randomization st...
Abstract 17970: Atrial Fibrillation is Associated With Increased Atrial Metabolic Activity on FDG/PET Imaging in Patients With Ischemic Cardiomyopathy
Authors: Nicolas D Santi, Rob Beanlands, Brian McArdle, Robert deKemp, Pablo Nery, Jennifer Renaud, Benjamin Chow, Renee Hessian, Ross Davies, Terrence Ruddy, Ann Guo, Tayebeh Hadizad, David Birnie
Journal: Circulation (2015)

Introduction: Atrial Fibrillation (AF) is a common arrhythmia but its pathogenesis remains incompletely understood. Alterations in metabolism may play a role. 18F-fluorodeoxyglucose (FDG) PET reflects glucose uptake in metabolically active tissue but studies evaluating the relationship between atrial FDG uptake and atrial fibrillation are limited. Hypothesis: We hypothesized that patients with ischemic cardiomyopathy who have had AF have increased atrial wall FDG uptake compared to patients without AF (no-AF). Methods: Atrial uptake was assessed visually and quantitatively on FDG-PET/CT images in 42 patients (24 AF, 18 no-AF). The maximum and mean FDG Standard Uptake Value (SUV) in the left atrium (LA), right atrium (RA) and mean blood pool activity were measured (see figure). The Tissue:Blood ratio (TBR) was calculated using the maximum atrial wall SUV (TBRmax) and mean SUV (TBRmean). Results: Median age was 72 years; (78% male). Mean LVEF was similar between AF vs. No-AF patients (24+/-10% vs. 26+/-11%, p=0.57). The RA was visualized in 88% of AF and 44% of no-AF patients (p=0.002). The LA was visualized in 88% of AF and 72% of no-AF patients (p=0.22). See table for TBR results. TBRmax and TBRmean were significantly increased in the RA wall of patients with AF vs. no-AF. There was a trend for increased FDG in the LA wall of AF patients. Conclusion: Among patients with ischemic cardiomyopathy, significantly greater FDG uptake was noted in the RA of patients with AF vs. No-AF (with a trend for LA uptake). These findings suggest increased glucose metabolism in the atria in patients with AF. Further study is warranted to determine the clinical and biological significance of these findings.
Metformin inhibits ovarian cancer cell growth in an AMP-kinase dependent manner and inhibiting mTOR pathway
Authors: Ramandeep Rattan, Shailendra Giri, Viji Shridhar
Journal: Cancer Research (2008)

1469  Metformin is the most widely used drug for type 2 diabetes. Metformin activates AMP-activated protein kinase (AMPK), which regulates cellular energy metabolism. Activation of AMPK has been shown extensively to cause growth arrest in multiple tumor types. Activation of AMPK by metformin has been shown to inhibit breast and colon cancer growth by inhibiting TSC-mTOR (mammalian target of rapamycin) pathway resulting in inhibition of protein synthesis. Recent population based studies have also suggested that the metformin use may be associated with reduced incidence and better prognosis for certain cancers. In the present study we investigated the anti-proliferative effect of metformin on ovarian cancer cell lines. Expression analysis of AMPK in ovarian cancer cell lines (VOSE, A2780, CP70, C200, OV202, OVCAR3 and SKOV3) indicated that they predominantly expressed AMPKα1 and β1 subunits. While the AMPK γ1 and γ2 subunits were variably expressed, AMPK γ3 subunit was not detected. Metformin treatment significantly inhibited proliferation of various ovarian cancer cell lines (A2780, CP70, C200, OV202, OVCAR3, DOV13 and SKVO3), as assessed by trypan blue exclusion and colony formation assays. Activation of AMPK by metformin resulted in an increase in its downstream targets, phospho- AMPK and phospho-ACC, as determined by western blot analysis in A2780, CP70, C200 and SKOV3 cells. Treatment with compound C, an AMP kinase inhibitor, protected ovarian cancer cells against metformin-induced growth arrest. Metformin induced growth inhibition was associated with decreased mTOR, S6 kinase, ribosomal protein S6 and eIF4E-binding protein 1 activation, and a general decrease in protein synthesis. Furthermore, metformin enhanced cisplatin induced cytotoxicity in colony formation assays, indicating that it can be used in combination with other chemotherapeutic drugs. These results provide the first evidence of metformin’s anti-growth effect in ovarian cancer and support the antineoplastic effects of metformin as an activator of AMP kinase in cancer prevention and treatment.
Genome-wide Copy-number Alterations in Circulating Tumor DNA as a Novel Biomarker for Patients with High-grade Serous Ovarian Cancer
Authors: Lara Paracchini, Luca Beltrame, Tommaso Grassi, Alessia Inglesi, Robert Fruscio, Fabio Landoni, Davide Ippolito, Martina Delle Marchette, Mariachiara Paderno, Marco Adorni, Marta Jaconi, Chiara Romualdi, Maurizio D'Incalci, Giulia Siravegna, Sergio Marchini
Journal: Clinical Cancer Research (2020)

High-grade serous epithelial ovarian cancer (HGS-EOC) is defined by high levels of somatic copy-number alterations (SCNA) with marked spatial and temporal tumor heterogeneity. Biomarkers serving to monitor drug response and detect disease recurrence are lacking, a fact which reflects an unmet clinical need.A total of 185 plasma samples and 109 matched tumor biopsies were collected from 46 patients with HGS-EOC, and analyzed by shallow whole-genome sequencing (sWGS). The percentage of tumor fraction (TF) in the plasma was used to study the biological features of the disease at the time of diagnosis (T0) and correlated with patients' survival. Longitudinal analysis of TF was correlated with CA-125 levels and radiological images to monitor disease recurrence.Gain in the clonal regions, 3q26.2 and 8q24.3, was observed in the 87.8% and 78.05% of plasma samples, suggesting that plasma sWGS mirrors solid biopsies. At T0, multivariate analysis revealed that plasma TF levels were an independent prognostic marker of relapse (P < 0.022). After platinum (Pt)-based treatment, circulating tumor DNA (ctDNA) analysis showed a change in the heterogeneous pattern of genomic amplification, including an increased frequency of amplification, compared with before Pt-based treatment in the 19p31.11 and 19q13.42 regions. TF in serially collected ctDNA samples outperformed CA-125 in anticipating clinical and radiological progression by 240 days (range, 37-491).Our results support the notion that sWGS is an inexpensive and useful tool for the genomic analysis of ctDNA in patients with HGS-EOC to monitor disease evolution and to anticipate relapse better than serum CA-125, the routinely used clinical biomarker.See related commentary by Dhani, p. 2372.
Tincture of Time: When to Implant a Prophylactic Cardioverter-Defibrillator Following Coronary Revascularization?⁎⁎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: Anne M. Gillis
Journal: Journal of the American College of Cardiology (2006)
IMMU-22. EARLY RELEASE OF TYPE I INTERFERON DRIVES BRAIN CANCER IMMUNOGENICITY AND RESPONSE TO IMMUNOTHERAPY
Authors: Brandon Wummer, Sadeem Qdaisat, Adam Grippin, Aida Karachi, Frances Weidert, Jianping Huang, Maryam Rahman, Duane Mitchell, Hector Mendez-Gomez, Elias Sayour
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Molecular drivers of cancer immunogenicity in brain tumors are still being unraveled. While BATF3 expression, STING, and interferon response factors (IRFs) are necessary for cancer immunogenicity, the presence of type I interferon (IFN-I) is contextual having been reported to elicit both anti-tumoral and pro-tumoral effects. A better understanding of IFN-I signaling mechanisms is necessary to elucidate drivers of brain cancer immunogenicity and resistance. OBJECTIVE We sought to assess the role of IFN-I signaling in brain tumor immunogenicity and response to immune checkpoint inhibitors (ICIs) in ICI sensitive brain tumor models (i.e. GL261). We then sought to develop strategies to reset IFN-I signaling in ICI resistant brain tumor models (i.e. KR158b). METHODS To reset IFN-I signaling in immunologically ‘cold’ tumors unresponsive to ICIs, we developed lipid-nanoparticles (NPs) to deliver mRNA payloads to the brain tumor microenvironment (TME). RESULTS In immune-sensitive GL261 tumors, we showed that early release of IFN-I unlocks cancer immunogenicity and ICI response. Blockade of IFN-I during tumorigenesis (within 24h, but not days later) increases tumorigenicity and abrogates ICI activity in sensitive tumors. In ICI resistant KR158b tumors, we show that systemic administration of tumor-derived RNA-NPs localize to myeloid cells within the TME for simultaneous activation of multiple innate pathways including BATF3 (necessary for effector DCs), IRF5 (necessary for M2 to M1 macrophage reprograming), and IRF7 (necessary for IFN-I production). These RNA-NPs induce near-immediate release of IFN-I (within hours), reprogram the brain TME in an IFNAR1 (IFN-I receptor) dependent manner, and elicit significant anti-KR158b efficacy as a monotherapy. Following IFNAR1 blockade, RNA-NP mediated anti-tumor efficacy was abrogated. We demonstrated safety of tumor-specific RNA-NPs (derived from KR158b) in acute/chronic GLP toxicity studies without normal-brain cross-reactivity, and confirmed feasibility/safety and immunologic activity in large-animal studies. FUTURE DIRECTIONS We have since received FDA-IND approval for first-in-human trials (IND#BB-19304) in glioblastoma patients.
TMOD-12. ESTABLISHING A CLINICALLY RELEVANT MODEL OF MESENCHYMAL GLIOBLASTOMA (GBM) TO STUDY RESPONSE TO STANDARD OF CARE TREATMENT AND IMMUNE CHECKPOINT INHIBITION (ICI).
Authors: James Clerkin, Kate Connor, Kieron Sweeney, Kieron White, Liam Shiels, Stephen Maher, Laure Marignol, Jochen H M Prehn, David O’Brien, Annette Byrne
Journal: Neuro-Oncology (2020)

Abstract GBM is a devastating disease with peak incidence in the seventh decade. Pre-clinical models are essential for studying resistance mechanisms and screening novel therapies. However, historically these models have failed to predict response in humans. Current models seldom incorporate surgical resection, and commonly use young animals whose immune contexture differs from older patients. Here, we have established an orthotopic model employing the syngeneic mesenchymal-NFpp10a-cell line which incorporates surgical resection in aged mice. We further characterise response to ICI and temozolomide monotherapy. NFpp10a and GL261-cell lines were exposed in vitro to irradiation (0Gy/2Gy/5Gy) and response assessed using colony formation assays. NFpp10a formed significantly more colonies at 5Gy compared to GL261 at both day 10 (NFpp10a 5.167 vs GL261 1.4; p=0.0017) and day 14 (NFpp10a 3.5 vs GL261 0; p&amp;lt; 0.0001). Hence, NFpp10a displays increased radioresistance. Next, NFpp10a-luciferin expressing cells were orthotopically implanted into young (6-8weeks;n=16) and aged (18months;n=16) C57BL/6-mice. Weekly bioluminescence imaging (BLI) was performed to monitor growth. Mice undergoing resection showed a median 18.47-fold drop in BLI signal. We demonstrated resection survival advantage in aged mice (Resection:33.5 days vs Non-Resection:18 days, p= 0.0166) and showed young age to be a positive prognostic factor (Young:62 days vs Aged:22 days, p=0.0002). Subsequently, we orthotopically implanted NFpp10a-Luc2 cells into C57BL/6 mice and treated with temozolomide (n=24) or PBS control (n=23), and anti-PD1 (n=24) or IgG (n=23). We observed that temozolomide and anti-PD1 monotherapy had no impact on NFpp10-Luc2 growth (temozolomide-overall:p=0.9001, anti-PD1-overall:p=0.7933) or survival (temozolomide-overall:p=0.3035, anti-PD1-overall:p=0.6328). Overall, we have established an NFpp10-Luc2 mesenchymal-GBM model in aged mice which incorporates surgical resection and accurately displays significant resistance to temozolomide and anti-PD1 monotherapy. We are currently employing this model to study the efficacy of neoadjuvant anti-PD1 therapy. Mechanistic analyses with multiplex-immunohistochemistry, scRNA and whole exome sequencing are planned to interrogate treatment effects on the tumor microenvironment.
Recapturing the Magic: Revisiting the Pleiotropic Effects of Statins in Percutaneous Coronary Revascularization⁎⁎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: Stephen G. Ellis, Saif Anwaruddin
Journal: Journal of the American College of Cardiology (2009)
RARE-32. PEDIATRIC METASTATIC SKULL BASE CHORDOMA WITH TP53 MUTATION – A CASE REPORT AND REVIEW OF THE LITERATURE
Authors: Akira Shimada, Kazuhiko Kurozumi, Kiichiro Kanamitsu, Hisashi Ishida Ishida, Kaori Fujiwara, Kana Washio Washio, Tadashi Kumamoto, Chitose Ogawa, Masahiro Shin
Journal: Neuro-Oncology (2020)

Abstract Chordoma is an uncommon bone tumor arising from notochordal remnant, which accounts for 1–4% of all bone malignancies. It commonly occurs along the cranial-spinal axis, and skull base is one of most frequent sites, representing 35–49% of all chordoma cases. Surgical resection is widely accepted as the first choice of treatment. There are only limited number of reports about pediatric chordoma cases, and its biological behavior including genetic backgrounds were largely unknown. Here, we present a 5 year-old girl with a large aggressive skull base chordoma of 6 cm in maximum diameter, which eventually had multiple systemic metastasis. We initially tried chemotherapy based on the protocol for the osteosarcoma, but in vain. Because the tumor was highly vascularized on angiography, after embolization of the feeding arteries and bilateral internal maxillary arteries, endoscopic endonasal surgery was performed. The tumor was sufficiently removed, achieving effective mass reduction, and the residual tumors involving the lower cranial nerves and craniocervial junction were additionally treated with Gamma Knife radiosurgery. However, one month later, it showed systemic metastasis to bilateral cervical lymph nodes and lung. We tried chemotherapy with nivolmab and imatinib for this patient, whereas they showed the partial effect. The genetic analysis revealed somatic TP53 c.569C&amp;gt;T, (p.P190L) mutation in chordoma specimen. In the past literature, we found only one study of the adult chordoma cases, in which majority of the patients had somatic TP53 mutation (p.P72R). Further investigation with large number of the cases is essential to clarify the molecular biology of pediatric chordomas.
OTHR-12. ANEURYSMAL BONE CYST RESEMBLING A POSTERIOR FOSSA TUMOR
Authors: Luis Angel Arredondo Navarro, Regina Malinali Navarro Martin Del Campo, Gutierrez Oliva Lorelay Livier, Valeria Estefania Aguilar Mercado, Juan Luis, Soto Mancilla
Journal: Neuro-Oncology (2020)

Abstract We presented the case of a 6-year-old boy who was seen in the emergency room because of signs of intracranial hypertension and left cerebellar syndrome. The CT scan revealed a heterogeneous lesion within the left hemisphere displacing the fourth ventricle and eroding the occipital bone. The MRI showed the same heterogeneous lesion majorly cystic, involving the bone and displacing the left cerebellar hemisphere. A minor hydrocephalus was evident in both studies. A suboccipital craniectomy was done and a cystic epidural tumor remodeling and eroding the bone was noted. The histopathological diagnosis corresponded to an aneurysmal bone cyst. Aneurysmal bone cyst is a rare benign tumor accounting for 3–6 % of tumors of the cranial base. We discuss the unusual location of the lesion.
CTNI-51. NEUROCOGNITIVE FUNCTION (NCF) OUTCOMES OF RTOG FOUNDATION 3508: A PHASE 3 TRIAL OF ABT-414 WITH CONCURRENT CHEMORADIATION AND ADJUVANT TEMOZOLOMIDE IN PATIENTS WITH EGFR-AMPLIFIED NEWLY DIAGNOSED GBM
Authors: Jeffrey S Wefel, Minhee Won, Andrew Lassman, Yaakov Stern, Tony Wang, Kenneth Aldape, Terri Armstrong, Michael Vogelbaum, Erik Sulman, Golnaz Moazami, Marian Macsai, Mark Gilbert, Earle Bain, Vincent Blot, Hui Gan, Matthias Preusser, Peter Ansell, Suvajit Samanta, Madan Kundu, Clemens Seidel, Filip de Vos, Sigmund Hsu, Andres Cardona, Giuseppe Lombardi, Dmitry Bentsion, Richard Peterson, Craig Gedye, Christine Lebrun-Frenay, Antje Wick, Stephanie Pugh, Walter Curran, Minesh Mehta
Journal: Neuro-Oncology (2020)

Abstract RTOG 3508/AbbVie M13-813/INTELLANCE-1 was a phase 3 trial of depatuximab-mafodotin (depatux-m, formerly ABT-414) that accrued 639 patients with EGFR-amplified newly diagnosed GBM. At the pre-specified interim OS analysis, the futility criteria were met and there was no survival benefit from adding depatux-m to SOC. Pre-specified secondary NCF analyses included time to decline in verbal learning and memory as assessed by the HVLT-R Total Recall based on the reliable change index. Exploratory NCF analyses examined changes in other HVLT-R outcomes over time. As corneal epitheliopathy causing visual impairment is a known toxicity of depatux-m, NCF tests that did not depend on visual acuity were employed. NCF testing occurred at baseline, day 1 of the first cycle of adjuvant depatux-m, every other cycle (i.e., 8 weeks) thereafter, and at progression. Compliance with test completion was 95% at screening and 80%, 70%, 58%, 51%, 47% thereafter through cycle 9. The most common reasons for missing data was site error. Time to HVLT-R Total Recall decline trended worse in the depatux-m arm compared to placebo but the difference was not significant (12 month deterioration: 41.2%, 95% CI: 3.50–47.2 vs 32.4%, 95% CI: 26.6- 38.4, p=0.052). The depatux-m arm, in comparison to the placebo arm, showed greater decline from baseline on the HVLT-R at the following time points: cycle 3 (Total Recall: mean= -1.8, SD=5.7 vs mean= -0.5, SD=5.5, respectively, p=0.046; Delayed Recall: mean= -1.1, SD=3.0 vs. mean= -0.2, SD=2.7, respectively, p=0.01), cycle 7 (Total Recall: mean= -0.6, SD=5.1 vs mean= 1.4, SD=5.0, respectively, p=0.009; Delayed Recall: mean -0.6, SD=3.0 vs. mean= 0.5, SD=2.7, respectively, p=0.01), and cycle 9 (Delayed Recall: mean=-0.4, SD=2.7 vs. mean= 0.8, SD=2.4, respectively, p=0.003). Depatux-m added to concurrent chemoradiation and adjuvant temozolomide was associated with faster time to deterioration and worse episodic learning and memory over time than placebo.