tbuckley/cabot-search huggingface dataset:
CTNI-73. OVERALL SURVIVAL OF NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS TREATED BY STANDARD THERAPY IN COMPARISON TO STANDARD THERAPY PLUS TUMOR TREATING FIELDS
Authors: Aaron Rulseh, Adam Derner, Jan Sroubek, Jan Klener, Josef Vymazal
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Tumor treating fields (TTFields; 200 kHz) have shown significant prolonged survival in newly diagnosed (ndGBM). TTFields are anti-mitotic, low intensity, intermediate frequency alternating electric fields. The applied fields disrupt the mitotic spindle, microtubule assembly and the segregation of intracellular organelles during cell division, leading to apoptosis or mitotic arrest. We compared overall survival (OS) between patients recently treated with standard therapy and standard therapy plus TTFields at our institution. METHODS Subjects (N=25) with ndGBM treated with standard therapy plus TTFields (STDTh-TTF) at our institution were included. Standard therapy (STDTh) consisted of surgical resection, followed by combined radiotherapy and chemotherapy (Temozolomide). In 3 cases, biopsies were performed instead of resection. The date of resection or biopsy was considered the entry date and was used in calculating survival. The study took place from July 2015 to April 2019. A matching control group of 25 subjects with ndGBM were treated with STDTh alone at our institution and were assembled from our database based primarily on date of resection or biopsy, and secondarily by age (2 subjects underwent biopsy in place of resection). When assembling the control group, the investigators were blinded to survival outcome. RESULTS Significantly greater overall survival was observed for the group treated by TTFields in addition to standard therapy (p &amp;lt; 0.001; Hazard ratio [HR] 0.21; 95% confidence interval [CI] 0.1–0.45; median survival time STDTh-TTF 31.7 months, STDTh 7.1 months). The groups were balanced with respect to sex, and no differences with respect to age (p = 0.13; STDTh-TTF mean 51.58 years, SD 8.8; STDTh mean 52.42 years, SD 8.7) or inclusion date (p = 0.22) by paired t-test were detected. CONCLUSIONS Our initial results appear promising with respect to overall survival benefit in patients undergoing TTFields treatment in addition to standard therapy.
Role of Echocardiography in Predicting Onset of Heart Failure in Patients With Stable Coronary Artery Disease: Is the Whole Greater Than the Sum of its Parts?⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Miguel A. Quinones
Journal: JACC. Cardiovascular imaging (2009)
NCMP-15. CNS LYMPHOMA: THE GREAT MIMICKER
Authors: Danielle Bazer, Agnes Kowalska
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Primary central nervous system lymphoma (PCNSL) is a variant of non-Hodgkin lymphoma, affecting the brain, leptomeninges, eyes, and spinal cord. PCNSL is a progressive disease with symptom onset occurring over weeks that presents with varied signs and symptoms, including focal neurological deficits, mental status changes, behavioral changes and seizures. Tissue diagnosis is imperative, though MRI, ophthalmologic and CSF evaluation can aid in diagnosis. PET scan and bone marrow biopsy are important for assessing metastatic spread following diagnosis. CASE PRESENTATION We present a case series, comprised of three patients with atypical presentations of CNS lymphoma. Patient 1. 64 year old male presented with facial muscle weakness, vertigo, and diplopia. Initial MRI showed an old thalamic and new internal capsule infarcts. EMG suggested sensorimotor peripheral neuropathy consistent with Guillain-Barre Syndrome, leading to treatment with a five day course of IVIG. His MRI findings gradually worsened, ultimately revealing leptomeningeal enhancement of the bilateral vestibulococchlear nerves, facial nerves and the trigeminal nerves. Patient 2. 66 year old male with a past medical history of primary cutaneous anaplastic T cell lymphoma stage 1 EA, status post field radiation, presented with aphasia and ataxia. Brain MRI showed extensive, enhancing hyperdensities in the midbrain, suggestive of multiple sclerosis, prompting treatment with steroids. He continued to clinically worsen, prompting tissue diagnosis. Patient 3. 66 year old male presented with recurrent syncopal episodes and aphasia, found to have a 4 cm extra axial mass in the left temporal region on MRI suggestive of a meningioma. CONCLUSION All three patients eventually underwent brain biopsy with a final histologic diagnosis of PCNSL. Due to the highly variable initial presentation of this condition and the wide range of pathologies it mimics, CNS lymphoma should be included in the differential diagnosis of patients presenting with atypical neuroimaging or clinical findings.
Advances in Acute Myeloid Leukemia Management: Focus on Secondary Disease and Older Patients
Authors: Daniel A. Pollyea
Journal: Journal of the National Comprehensive Cancer Network (2020)

The “Age of Induction” led to breakthroughs in the treatment landscape for acute myeloid leukemia (AML), and was immediately followed by a long period during which few drugs were approved. That all changed a few years ago, when 2017 began the “Age of Abundance.” With many treatment options now available, new management strategies have emerged for patients with secondary AML, as well as for older patients with AML. Treatment can now be tailored to these special populations, and providers should be aware of the unique supportive care considerations associated with these newer AML therapies.
MBCL-09. ISOLATED M1 METASTASES IN PEDIATRIC MEDULLOBLASTOMA: IS POSTOPERATIVE RADIOTHERAPY FOLLOWED BY MAINTENANCE CHEMOTHERAPY SUPERIOR TO POSTOPERATIVE SANDWICH-CHEMOTHERAPY AND RADIOTHERAPY?
Authors: Denise Obrecht, Martin Mynarek, Christian Hagel, Robert Kwiecien, Michael Spohn, Michael L Bockmayr, Brigitte Bison, Monika Warmuth-Metz, Stefan M Pfister, David T W Jones, Dominik Sturm, Andreas von Deimling, Felix Sahm, Katja von Hoff, B - Ole Juhnke, Martin Benesch, Nicolas U Gerber, André O von Bueren, Carsten Friedrich, Rolf-Dieter Kortmann, Rudolf Schwarz, Torsten Pietsch, Stefan Rutkowski
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Impact of isolated spread into the cerebrospinal fluid (CSF) is still not investigated comprehensively for childhood medulloblastoma and the best therapeutic strategy is currently unclear. MATERIAL AND METHODS Sixty-six patients with isolated M1-MB registered to the HIT-MED-database from 2000–2018 were identified. CSF and MRI were centrally reviewed for all patients. Patients were stratified by age and either treated with upfront craniospinal irradiation (CSI) followed by maintenance chemotherapy (CT) or with postoperative CT and delayed CSI. RESULTS Forty-nine patients were non-infants ≥4 years and seventeen were infants &amp;lt;4 years. Median age was 7.3y (1.1–18.0). 83.3% were histologically classified as CMB, 12.1% as LCA-MB and 4.6% as DMB. Molecular subgroup was Gr.3 in 25.8%, Gr.4 in 28.8%, SHH in 4.5%, WNT in 1.5% and not evaluated for 39.4%. Lumbar puncture was performed on median postoperative day 19 (range: 14–77). Median follow-up for survivors was 7.6y (range: 1.2–15.9). The whole cohort showed a 3y- and 5y-PFS of 68.0(±6.0) and 60.0(±6.5)%, while OS was 79.1(±5.2) and 72.9(± 5.9)%. 10y-OS was 54.4(±7.5). Patients with upfront CSI had more favourable outcomes (5y-PFS 66.1 vs. 55.8% [p=0.119]; 5y-OS 90.6 vs. 64.5% [p=0.035]). The trend towards improved survival in patients with postoperative CSI was retained when only non-infants were considered (pPFS=0.176, pOS=0.055). M1-persistence occurred exclusively in patients with postoperative CT. CONCLUSION Isolated M1-MB is rare. Patients without contraindication for CSI appear to benefit from treatment by upfront CSI followed by maintenance CT, while cumulative CT-doses would be reduced compared to sandwich strategies.
The Sheba Medical Center healthcare workers' children's school: can we open schools safely?
Authors: Or Kriger, Yaniv Lustig, Carmit Cohen, Sharon Amit, Asaf Biber, Galia Barkai, Liron Talmi, Shiraz Gefen-Halevi, Bella Mechnik, Gili Regev-Yochay
Journal: Clinical Microbiology and Infection (2020)
TAMI-26. SINGLE-CELL TRANSCRIPTOME ANALYSIS REVEALS THAT ENDOTHELIAL TRANSFORMATION DRIVES GLIOBLASTOMA CHEMORESISTANCE VIA Wnt/β-CATENIN/MRP-1
Authors: Menggui Huang, Duo Zhang, Yi Fan
Journal: Neuro-Oncology (2020)

Abstract Therapeutic resistance remains a persistent challenge for patients with glioblastoma (GBM). Here, we report that endothelial cells (ECs) acquire transformation into mesenchymal stem cell (MSC)-like cells in GBM, driving tumor resistance to cytotoxic treatment. Single-cell transcriptome analysis identified an EC-derived cell population that robustly expresses mesenchymal genes and stem cell-associated markers, suggesting that ECs undergo mesenchymal transformation and stemness-like activation in GBM microenvironment. Furthermore, we identified a c-Met-mediated axis that induces β-catenin phosphorylation at Ser675 and Wnt signaling activation, inducing multidrug resistance-associated protein-1 (MRP-1) expression and leading to EC stemness-like activation and chemoresistance. Last, genetic ablation of β-catenin in ECs overcome GBM tumor resistance to temozolomide (TMZ) chemotherapy in vivo. Combination of Wnt inhibition and TMZ chemotherapy eliminated tumor-associated ECs, inhibited GBM growth, and increased mouse survival. These findings identified a cell plasticity-based, microenvironment-dependent mechanism that controls tumor chemoresistance, and suggest that targeting Wnt/β-catenin-mediated EC transformation and stemness activation may overcome therapeutic resistance in GBM.
IMMU-19. HDAC INHIBITORS SENSITIZE MYC-AMPLIFIED MEDULLOBLASTOMA TO IMMUNOTHERAPY BY ACTIVATING THE NF-kB PATHWAYS
Authors: Viktoria Marquardt, Johanna Theruvath, David Pauck, Daniel Picard, Guido Reifenberger, Arndt Borkhardt, Samuel Cheshier, Thomas Kurz, Marc Remke, Siddhartha Mitra
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma is the most common malignant brain tumor in childhood and comprises four distinct molecular subgroups with further layers of intertumoral heterogeneity. Amplification of the oncogene MYC drives tumorigenesis and constitutes a hallmark feature underlying Group 3 biology. Employing our in-house drug screening pipeline, we evaluated a library of epigenetic inhibitors (n=78) in various brain tumor cell lines followed by a secondary HDACi library (n=20) screen, we identified the clinically established, class I selective HDACi CI-994 as the compound with the most preferential antitumoral effect in MYC-driven medulloblastoma. We confirmed that the inhibitor response was in part MYC-dependent as our lentiviral-based MYC-overexpression model showed higher sensitivity towards CI-994 treatment as compared to the isogenic control with low endogenous MYC expression. CI-994 showed significant antitumoral effects at the primary site and at the metastatic compartment in two orthotopic mouse models of MYC-driven medulloblastoma. RNA sequencing profiling of tumor cells treated with CI-994 at IC50 revealed an up-regulation of multiple innate inflammatory pathways like NFκB, TLR4, Interferon-gamma, and TGFbeta. Flow cytometry analysis revealed an increased surface expression of MHC-I. We combined CI-994 with an anti-body against the innate checkpoint CD47 which acts as a “don’t eat me” signal previously shown by us to have significant anti-tumor activity against MYC-driven MB. Combining CI-994 with anti-CD47 shows a significant increase in macrophage-mediated phagocytosis of tumor cells and a significant increase in the survival of tumor-bearing mice.
HGG-48. ROS1 INHIBITOR ENTRECTINIB USE IN RELAPSE/REFRACTORY INFANTILE GLIOBLASTOMA WITH POSITIVE ROS1 FUSION - A CASE REPORT WITH PROMISING RESPONSE
Authors: Dennis Tak-Loi Ku, Matthew Ming-Kong Shing, Godfrey Chi-Fung Chan, Eric Fu, Ping-Wa Yau, Chung-Wing Luk, King-Fai Cheng, Wilson Wai-Shing Ho, Ho-Keung Ng, Yin-Chung Po, Alvin Siu-Cheung Ling
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Infantile glioblastoma is rare with poor prognosis. Recent molecular study for infantile hemispheric high grade glioma found its association with ALK/ROS1/NTRK/MET pathway. This suggested the potential use of targeted therapy for refractory / relapse patients. CASE: A newborn presented with apnea, CT brain showed intracranial haemorrhage. MRI then showed a left parietal tumour with bleeding and mass effect. Craniotomy achieved subtotal resection. Chemotherapy VCR/CPM alternating with CDDP/VP-16 was given for one year. Patient was stable with static residual tumour during chemotherapy. However patient developed status epilepticus two weeks after off treatment. MRI showed significant tumour progression which required 2nd &amp; 3rd debulking surgery. Molecular assay by nanostring panel showed BRAF-KIAA1549 fusion. MEK inhibitor Trametinib was tried for 3 months and stopped as disease progression. Further molecular assay by RNASeq showed presence of ROS1 fusion (ZCCHC8-ROS1) while absent of BRAF fusion. Patient underwent 4th debulking surgery as impending herniation while waiting for the targeted therapy. It was complicated with right hemiplegia and facial nerve palsy postoperatively. Finally, ROS1 inhibitor Entrectinib was started 2 weeks later. It was well tolerated without significant adverse reaction. Patient made dramatic neurological recovery including improved facial nerve palsy, able to walk unaided and self feed. MRI brain 1 and 3 months after Entrectinib showed interval reduction in residual tumour. Patient is currently progression-free for 6 months. CONCLUSION Early molecular study for infantile glioblastoma is useful to guide novel therapy. Molecular result may varies between different panels or change over time, to be interpreted with caution.
DDRE-19. SPIDER VENOMS AS SOURCES OF MOLECULES FOR NEW CANCER TREATMENTS: THE EFFECTS OF THE SNX-482 PEPTIDE ON MACROPHAGE MODULATION
Authors: Jaqueline de Lima Munhoz, Rodolfo Thome, Larissa Ishikawa, Natalia Barreto dos Santos, Thomaz A A da Rocha-e-Silva, Rafael Sutti, Liana Verinaud, João Luiz Vitorino Araujo, Abdolmohamad Rostami, Catarina Raposo
Journal: Neuro-Oncology (2020)

Abstract Malignant primary brain tumors remain among the most difficult cancers to treat. In malignant tissues, macrophages are accumulated in a high infiltration being known as tumor-associated macrophages (TAMs). These cells are associated with poor prognostics in many types of cancer. Studies in our group demonstrated that the venom of Phoneutria nigriventer (PnV), a wandering spider from South America, has reduced the development of glioblastoma (GBM) in a murine model, inducing a large infiltrate of TAMs. Subsequently, in vitro results demonstrated that PnV activates macrophages, increasing the ability to kill tumor cells. The aim of this study was to analyze the effects of the peptide SNX-482 presented in the venom of Hysterocrates gigas in macrophages for further correlation with the PnV. Macrophages were differentiated from bone marrow precursors collected from male C57BL6 mice and differentiated for 7 days with M-CSF. These cells were used for polarization and coculture with T cells and analyzed by flow cytometry. PCR Array was also performed (QIAGEN) for the analysis of gene expression. The results showed that SNX-482 could activate macrophages in a not dose-dependent response. There was an increase in the main activation markers (CD40, CD80, CD86, CD68, CD83, and MHCII). The polarization indicated that the peptide potentiated the proinflammatory effect of M1 macrophages (increased MHCII and iNOS). The screening of 86 cancer-related genes showed that the Ccr4, Pdcd1, Gzmb, and IFN-γ genes had an increase in their expression. Furthermore, we developed in C57BL/6 mouse a pre-clinical model of intracranial glioblastoma using the Gl261 cell line. The results showed an applied-easy-safe model that could alter the gene expression of cancer markers. Taken together, all the results contributed to increasing the knowledge about the peptide SNX-482 and the model for further pre-clinical assays of glioblastoma, making a great advance in the development of new treatments.
NIMG-48. USE OF MOBILE LIPIDS AS METABOLIC MARKERS FOR THE ASSESSMENT OF TREATMENT-INDUCED NECROSIS IN A RECURRENT GLIOBLASTOMA PATIENT TREATED WITH A NEW OSCILLATING MAGNETIC FIELD GENERATING DEVICE
Authors: Kumar Pichumani, Omkar Ijare, Martyn Sharpe, Lisa Nguyen, Santosh Helekar, David Baskin
Journal: Neuro-Oncology (2020)

Abstract The FDA has approved tumor treating fields (Optune) to treat glioblastoma (GBM) and unresectable mesothelioma. Optune uses scalp electrodes to pass a strong alternating electric field through the head, slowing GBM growth. We have recently developed and tested a novel device that uses an oscillating magnetic field (OMF) generated by rotating magnets to treat GBM. Our first GBM patient had a recurrent GBM with leptomeningeal spread. A custom-made Oncomagnetic device consisting of a multi-sport helmet with three OMF generators called oncoscillators, was worn by the patient at home. Changes in the brain and GBM tumor metabolism were examined using in vivo1H MRS on a 7T Siemens MRI scanner. 1H MRS data of the “tumor” and “non-tumor” regions during OMF treatment was obtained using sLASER pulse sequences. Both non–tumor and tumor regions showed the most common brain metabolites – myo-inositol, creatine, choline, glutamine/glutamate, and N-acetyl aspartate (NAA). 30 days after initiation of treatment, choline, creatine and NAA levels in the shrunken tumor region had collapsed. The tumor region displayed broad proton signals centered at 1.30 ppm and 0.88 ppm. These peaks have been observed following successful brain tumor radiation therapy and have been attributed to the presence of mobile lipids due to tumor necrosis. Our in vitro experiments suggest OMF-induced damage to mitochondria and elevated levels of reactive oxygen species, leading to cancer cell death via apoptosis and necrosis. We propose that loss of choline and elevation of lipid levels may be used as a metabolite ‘fingerprint’ to noninvasively assess the Oncomagnetic treatment response. This powerful new treatment holds great promise for treatment of patients with GBM, and produces rapid changes in brain chemistry during treatment.
New agents and regimens for diffuse large B cell lymphoma
Authors: Liang Wang, Lin-rong Li, Ken H. Young
Journal: Journal of Hematology & Oncology (2020)

Abstract As a widely recognized standard regimen, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is able to cure two-thirds patients with diffuse large B cell lymphoma (DLBCL), and the remaining patients suffer from refractory or relapsed disease due to resistance to R-CHOP and fare poorly. Unsatisfied outcomes for those relapsed/refractory patients prompted efforts to discover new treatment approaches for DLBCL, including chimeric antigen receptor T cells, bispecific T cell engagers, immunomodulatory drugs, immune checkpoint inhibitors, monoclonal antibodies, antibody–drug conjugates, molecular pathway inhibitors, and epigenetic-modifying drugs. Herein, up-to-date data about the most promising treatment approaches for DLBCL are recapitulated, and novel genetic classification systems are introduced to guide individualized treatment for DLBCL.
GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma
Authors: Jeong A. Park, Nai-Kong V. Cheung
Journal: Journal of Hematology & Oncology (2020)

The cure rate for metastatic osteosarcoma has not substantially improved over the past decades. Clinical trials of anti-HER2 trastuzumab or anti-GD2 dinutuximab for metastatic or refractory osteosarcoma were not successful, and neither was immune checkpoint inhibitors (ICIs).We tested various target antigen expressions on osteosarcoma cell lines using flow cytometry and analyzed in vitro T cell engaging BsAb (T-BsAb)-dependent T cell-mediated cytotoxicity using 4-h 51Cr release assay. We tested in vivo anti-tumor activities of T-BsAb targeting GD2 or HER2 in established osteosarcoma cell line or patient-derived xenograft (PDX) mouse models carried out in BALB-Rag2-/-IL-2R-γc-KO (BRG) mice. We also generated ex vivo BsAb-armed T cells (EATs) and studied their tumor-suppressive effect against osteosarcoma xenografts. In order to improve the anti-tumor response, ICIs, anti-human PD-1 (pembrolizumab) or anti-human PD-L1 (atezolizumab) antibodies were tested their synergy with GD2- or HER2-BsAb against osteosarcoma.GD2 and HER2 were chosen from a panel of surface markers on osteosarcoma cell lines and PDXs. Anti-GD2 BsAb or anti-HER2 BsAb exerted potent anti-tumor effect against osteosarcoma tumors in vitro and in vivo. T cells armed with anti-GD2-BsAb (GD2-EATs) or anti-HER2-BsAb (HER2-EATs) showed significant anti-tumor activities as well. Anti-PD-L1 combination treatment enhanced BsAb-armed T cell function in vivo and improved tumor control and survival of the mice, when given sequentially and continuously.Anti-GD2 and anti-HER2 BsAbs were effective in controlling osteosarcoma. These data support the clinical investigation of GD2 and HER2 targeted T-BsAb treatment in combination with immune checkpoint inhibitors, particularly anti-PD-L1, in patients with osteosarcoma to improve their treatment outcome.
NURS-04. COMBINATION OF NEURO-ONCOLOGY AND DERMATOLOGY CLINICS IMPROVE THE MANAGEMENT AND KNOWLEDGE OF SKIN-RELATED TOXICITIES WITH MEK AND BRAF TARGETED THERAPY
Authors: Tara McKeown, Irene Lara-Corrales, Andrea Cote
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The recent advancement in treating pediatric low grade glioma has led to upfront use of MEK and BRAF (MAPK) inhibitor therapy. At the Hospital for Sick Children we are the National leaders in treating pediatric oncology diagnosis with MAPK therapies. DESIGN: After treating several patients on MAPK inhibitors with various degrees of skin toxicity, we found we had poor and inconsistent access to dermatology services and as oncology practitioners had limited front-line knowledge about skin management. It was determined that a more formalized expertise and time with dermatology was needed. In 2018, in combination with the dermatology team, our new agents and innovative therapy and the nursing team we collaborated to develop a combined oncology and dermatology clinic. This clinic occurs twice a month to give our families and oncology teams better front-line access to dermatology knowledge and care. RESULTS The dermatology and oncology team have collaborated to provide information sessions for the oncology medical team about current research, skin grading and education. This combined approach has allowed us to ensure that each new family starting MAPK inhibitor therapy undergoes a baseline skin assessment, education on prophylactic skin measures and easier access to dermatology within their oncology clinic. We are also developing guidelines to consistently treat common skin related toxicities. CONCLUSION The early involvement of the dermatology clinic and increase knowledge with the nursing and medical team has allowed our families to gain confidence in managing skin related complication and reducing the need to hold targeted therapies as a result of dermatological toxicity.