tbuckley/cabot-search huggingface dataset:
EPID-21. EPIDEMIOLOGY OF MALIGNANT GLIOMAS IN KOREA USING NATIONWIDE BIG DATA FROM 2007 TO 2017
Authors: Seung Ho Yang
Journal: Neuro-Oncology (2020)

Abstract The purpose of the study of the study is to investigate the incidence, prevalence, and survival of malignant glioma (MG) using population-based Korean National Health Insurance Database (NHID) data. We identified patients with MG as C71 codes in KCD 5–7 according to ICD-10 from 2007 to 2017. Epidemiological characteristics of MG, including annual incidence, prevalence, mortality rates, and survival rates, were collected and analyzed according to socioeconomic state (SES) and treatment modalities. 45,066 new patients with MG were identified from 2007 to 2017. An age-adjusted incidence of 7.47 per 100,000 people. The mean age at diagnosis was 54 years. The male to female ratio was 1.11. Mortality and survival probability were analyzed among total subjects and in subgroups. The mortality of female patients was lower than that of male patients (hazard ration, 0.69; 95% CI, 0.67–0.71), and younger age and higher income had significantly lower mortality rate. The 1-, 3-, 5-, and 10-year total relative survival rates were estimated at 63.4%, 46.2%, 39.4%, and 34.8%, respectively. This is the first population-based study to determine the incidence and prevalence of MG according to epidemiological characteristics in Korea using NHID data. Our study found that female sex and high SES were factors that significantly lowered the mortality rate in MG, and younger groups and operated patients showed significantly higher survival rates.
NCOG-51. CORRELATION BETWEEN TUMOR VOLUME AND SERUM PROLACTIN AND IMPACT OF TUMOR CELLULAR DENSITY ON PROLACTINOMA SURGICAL OUTCOMES IN A COHORT OF 181 PATIENTS
Authors: Matheus Pereira, Taemin Oh, Rushikesh Joshi, Alexander Haddad, Kaitlyn Pereira, Robert Osorio, Kevin Donohue, Zain Peeran, Sweta Sudhir, Saket Jain, Angad Beniwal, José Gurrola, Ivan El-Sayed, Lewis Blevins, Philip Theodosopoulos, Sandeep Kunwar, Manish Aghi
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Prolactinomas are common pituitary adenomas managed medically or surgically. METHODS Reviewed 181 prolactinomas resected transsphenoidally 2012-2019. Tumor volumes were quantified using BrainLab Smartbrush. Pearson correlation analysis and linear regression were used to identify associations between tumor volumes and serum prolactin. Tumor density was defined as serum prolactin divided by tumor volume. RESULTS Mean tumor volume was 6.33cm3 and mean pre-op prolactin was 803.4ug/L, with men having larger (12.11 vs 2.93cm3;p&amp;lt; 0.001) and women having denser (173.9 vs 107.6ug/L/cm3;p=0.011) prolactinomas. Pearson correlation (R=0.688;p&amp;lt; 0.001) and linear regression revealed a strong association between pre-op volume and prolactin levels, with 96.9g/L increase in prolactin/cm3 increase in volume (p&amp;lt; 0.001); this holds true for men (R=0.584;p&amp;lt; 0.001) and women (R=0.939;p&amp;lt; 0.001), with women demonstrating greater prolactin/cm3 tumor density (186.5 vs 75.0ug/L;p&amp;lt; 0.001). MiB index did not correlate with pre-op volume (p=0.449) or pre-op prolactin (p=0.452). Logistic regression showed decreased biochemical remission with increasing pre-op volume (OR=0.891;p&amp;lt; 0.001). Increased MiB index (p=0.971) and p53 (p=0.525) staining did not affect remission rates. Positive PIT-1 staining was associated with higher remission rates (OR=2.508;p=0.005). Patients without remission had denser tumors (149.9 vs. 100.6ug/L/cm3;p=0.013), with Pearson correlation yielding R=0.736 between pre-op volume and pre-op prolactin (p&amp;lt; 0.001), and R=0.476 between residual volume and post-op prolactin (p&amp;lt; 0.001). Patients without remission exhibited 142.9ug/L increase in prolactin/cm3 of pre-op volume (p&amp;lt; 0.001), higher than the 58.9ug/L increase in prolactin/cm3 in patients with remission (p&amp;lt; 0.001). Patients without remission had residual tumors with 68.4ug/L increase in prolactin/cm3 of remaining volume after resection (p&amp;lt; 0.001). CONCLUSION Our analysis revealed significant correlation between prolactinoma volume and serum prolactin levels. Patients without remission had greater tumor cellular density than those with remission. The volume-prolactin correlation persisted post-operatively, although surgery reduced tumor density. These results could identify prolactinomas for which surgery could achieve biochemical remission.
Tweak to Treat: Reprograming Bacteria for Cancer Treatment
Authors: Brendan Fu-Long Sieow, Kwok Soon Wun, Wei Peng Yong, In Young Hwang, Matthew Wook Chang
Journal: Trends in cancer (2020)

Recent advancements in cancer biology, microbiology, and bioengineering have spurred the development of engineered live biotherapeutics for targeted cancer therapy. In particular, natural tumor-targeting and probiotic bacteria have been engineered for controlled and sustained delivery of anticancer agents into the tumor microenvironment (TME). Here, we review the latest advancements in the development of engineered bacteria for cancer therapy and additional engineering strategies to potentiate the delivery of therapeutic payloads. We also explore the use of combination therapies comprising both engineered bacteria and conventional anticancer therapies for addressing intratumor heterogeneity. Finally, we discuss prospects for the development and clinical translation of engineered bacteria for cancer prevention and treatment.
<i>Notes from the Field:</i> First Case in the United States of <i>Neisseria gonorrhoeae</i> Harboring Emerging Mosaic <i>penA</i>60 Allele, Conferring Reduced Susceptibility to Cefixime and Ceftriaxone
Authors: Michael A. Picker, Ronald J. Knoblock, Holly Hansen, Ilene Bautista, Rey Griego, Lora Barber, William Bendik, Kit Lam, Elizabeth Adelman, Zuwen Qiu-Shultz, Brian H. Raphael, Cau D. Pham, Ellen N. Kersh, Hillard Weinstock, Sancta B. St. Cyr
Journal: MMWR Morbidity and Mortality Weekly Report (2020)
Abstract 13508: Advanced Glycation End Products Formation Drives Structural Bioprosthetic Valve Degeneration
Authors: Yingfei Xue, Antonio Frasca, Samuel Keeney, Andrey Zakharchenko, Alexander Kossar, Robert Levy, Giovanni Ferrari
Journal: Circulation (2019)

Introduction: Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde crosslinked heterografts are widely used to treat severe heart valve disease. However, BHV often need to be replaced af...
ATRT-03. IDENTIFICATION OF microRNA-BASED PROGNOSTIC BIOMARKERS AND CANDIDATE THERAPEUTIC AGENTS FOR ATYPICAL TERATOID/RHABDOID TUMOR
Authors: Yang Zhang, Jianguo Xu
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND MicroRNA (miRNA) has been found to be involved in development of many malignant pediatric brain tumors, including atypical teratoid/rhabdoid tumor (AT/RT) that is highly aggressive and carries a dismal prognosis. The current study investigated the potential value of miRNAs and pivotal genes associated with AT/RT using bioinformatics analysis, aiming to identify new prognostic biomarkers and candidate drugs for AT/RT patients. METHODS Differentially expressed miRNAs (DEMs) and genes (DEGs) between AT/RT and normal control samples were obtained from GEO database. The target genes of DEMs were predicted via TargetScanHuman7.2 and miRDB, and then intersected with DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of overlapping genes were conducted, followed by construction of protein-protein interaction network. Hub genes were determined by Cytoscape software, and their prognostic values were evaluated using Kaplan-Meier analysis. Connectivity Map database was used to identify latent therapeutic agents. RESULTS A total of 11 DEMs (hsa-miR-1224-5p, hsa-miR-128-3p, hsa-miR-17-5p, hsa-miR-18b-5p, hsa-miR-29c-5p, hsa-miR-329-3p, hsa-miR-379-5p, hsa-miR-433-3p, hsa-miR-488-5p, hsa-miR-656-3p and hsa-miR-885-5p) were screened. By intersecting 3275 predicted target genes and 925 DEGs, we finally identified 226 overlapping genes that were enriched in pathways in cancer and MAPK signaling pathway. Four hub genes (GRIA2, NRXN1, SLC6A1 and SYT1) were significantly associated with the overall survival of AT/RT patients. Candidate drugs included histone deacetylase inhibitor (givinostat), DNA synthesis inhibitor (floxuridine), cyclin-dependent kinase inhibitor (purvalanol) and janus kinase inhibitor (lestaurtinib). CONCLUSION In summary, this study systematically analyzed AT/RT-related miRNAs and pivotal genes to provide novel prognostic biomarkers and potential therapeutic agents.
Patterns of Resistance Differ in Patients with Acute Myeloid Leukemia Treated with Type I versus Type II FLT3 Inhibitors
Authors: Ahmad S. Alotaibi, Musa Yilmaz, Rashmi Kanagal-Shamanna, Sanam Loghavi, Tapan M. Kadia, Courtney D. DiNardo, Gautam Borthakur, Marina Konopleva, Sherry A. Pierce, Sa A. Wang, Guilin Tang, Veronica Guerra, Bachar Samra, Naveen Pemmaraju, Elias Jabbour, Nicholas J. Short, Ghayas C. Issa, Maro Ohanian, Guillermo Garcia-Manero, Kapil N. Bhalla, Keyur P. Patel, Koichi Takahashi, Michael Andreeff, Jorge E. Cortes, Hagop M. Kantarjian, Farhad Ravandi, Naval Daver
Journal: Blood Cancer Discovery (2020)

Despite promising results with FLT3 inhibitors (FLT3i), response durations remain short. We studied pretreatment and relapse bone marrow samples from patients with FLT3-mutated AML treated with FLT3i-based therapies (secondary resistance cohort), and pretreatment bone marrow samples from patients with no response to FLT3i-based therapies (primary resistance cohort). Targeted next generation sequencing at relapse identified emergent mutations involving on-target FLT3, epigenetic modifiers, RAS/MAPK pathway, and less frequently WT1, and TP53. RAS/MAPK and FLT3-D835 mutations emerged most commonly following type I and type II FLT3i-based therapies, respectively. Patients with emergent mutations at relapse had inferior overall survival compared with those without emergent mutations. Among pretreatment RAS mutated patients, pretreatment cohort level variant allelic frequencies for RAS were higher in non-responders, particularly with type I FLT3i-based therapies, suggesting a potential role in primary resistance as well. These data demonstrate distinct pathways of resistance in FLT3-mutated AML treated with type I versus II FLT3i.
TAMI-47. EVALUATION OF THE EFFECT OF MICROENVIRONMENTAL STRESSES ON GLIOMA STEMNESS IN VITRO AND EX VIVO
Authors: Vasiliki Pantazopoulou, Tracy Berg, Alexander Pietras
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma is the highest-grade glioma and most aggressive brain tumor, affecting both adults and children. Treatment includes surgery followed by chemotherapy, most frequently in the form of temozolomide treatment, radiation and in some cases by application of tumor-treating fields. Tumor recurrence is very common and is driven by cells exhibiting a treatment-resistant cancer stem cell phenotype, located in specific niches, namely the hypoxic and perivascular niche. While previous studies have delved into the role of the microenvironment in supporting glioma stemness and therapy resistance, little is known about how the stromal cells themselves respond to microenvironmental stresses. Here, we show that one cell type of the tumor microenvironment, the astrocyte, becomes activated after treatment with radiation, temozolomide or hypoxia in vitro, showing an increase in GFAP and Vimentin expression as well as morphological changes. Activated astrocytes also change their secretome, secreting cytokines such as IL6, IL7, CCL2 and CCL8, all associated with worse prognosis in several patient cohorts. Importantly, conditioned medium or extracellular matrix from activated astrocytes induce stemness features in glioma cells, measured by increased side population or radiation resistant fractions. To evaluate our findings in a more relevant model, we use an ex vivo organotypic culture system for brain sections from our experimental mouse model of glioma. Cultures are maintained for up to 21 days in 21%, 5% or 1% O2 with a high proportion of surviving tumor and stromal cells. We intend to use the ex vivo system to evaluate the effect of microenvironmental stresses on glioma stemness. Our study suggests that the tumor microenvironment that has been exposed to stressors such as radiation, chemotherapy or hypoxia is important in maintaining stemness and therefore treatment resistance in glioblastoma. Further research is required to address these stress-induced changes and provide better treatment options for glioblastoma patients.
INNV-29. PROFESSIONAL PRACTICE MODEL FOR ADVANCED PRACTITIONERS IN NEURO ONCOLOGY
Authors: Christina Cone, Mary Affronti
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Neuro-oncology advanced practitioners (APs - nurse practitioners, physician assistants) require specialization beyond the scope of population-based generalist training and education. There are no specialty standards or certifications for neuro-oncology APs, no formal training programs, and no literature that addresses the competency requirements of neuro-oncology APs. The burden of AP turnover at an academic medical center ambulatory neuro-oncology practice was as high as 50%. This quality improvement project’s purpose was to develop a professional practice model (PPM) to support the professional development and retention of APs. METHODS Using the Focus, Analyze, Develop, Execute and Evaluate (FADE) quality improvement methodology the authors (1) reviewed literature and relevant professional organizations to identify possible professional competencies for neuro-oncology APs, (2) analyzed data to develop evidenced-based practice domains, (3) used purposive sampling to recruit a team of neuro-oncology experts, (4) conducted a Delphi study with the experts to gain consensus on practice domains and professional competencies, and finally (5) utilized the Delphi study results to create a PPM for neuro-oncology APs. RESULTS The authors recruited twenty-three participants (39% were physicians, 57% were APs, and 4% were administrators) for the Delphi study, which was executed via electronic transmission using Qualtrics. Participants reached consensus on six domains of practice (Medical Knowledge, Interprofessional Collaboration/Communication, System-based Practice, Professionalism, Practice-based learning, Patient/family-centered care) and fifty corresponding competency statements after two rounds of the Delphi. With the implementation of the PPM and the development of standardized onboarding, the AP turnover rate decreased from 50% to 12% in just two years. CONCLUSION This QI project successfully created a PPM for a neuro-oncology AP team. The PPM supports neuro-oncology APs by validating their unique skill set that combines several specialties. The PPM provided the framework to standardize orientation/training, evaluate performance, and promote job satisfaction and retention.
LINC-01. COMPLIANCE TO FOLLOW UP IN PEDIATRIC PATIENTS WHO HAVE RECEIVED CRANIOSPINAL IRRADIATION
Authors: Khin Pyone, Thwe Tun, Yin Win, Aye Thinn, Khin Win, Tint Hnin, Aye Khaing
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE Attendance to follow-up after completion of cancer treatment is understudied area. Pediatric cancer patients have sequelae of illness or treatment. Many have no symptom immediately after completion of treatment. Long term follow-up is important to access disease control, early diagnosis of recurrence, second cancer and treatment-related morbidities. Purpose of this study was to evaluate the compliance to follow-up in pediatric patients treated with craniospinal irradiation (CSI). METHODS This was retrospective review of follow-up in pediatric neuro-oncology patients who received (CSI) from January 2017 to June 2018 in the Radiotherapy Department of Yangon General Hospital, Myanmar. RESULT: Twenty-three patients received CSI; majority (43%) were medulloblastoma. Median age was 7.5 years (3–17 years). Only seven patients (30.4%) were attended to follow-up more than 6 months after completion of treatment. More than two-thirds of patients (n=16,69.6%) were lost to follow-up. Patients in active follow-up were diagnosed and treated at earlier age below 10years (n=5,21.7%). Demographically, 5 patients (22%) were living in the region around tertiary hospital. Sixteen patients (69.6%) from rural area had limited transportation and difficulty for accommodation in which they were treated. In socioeconomic points, 18 parents (78.2%) had poor education and financial status, lack of understanding about disease, treatment, long-term effects and follow-up. CONCLUSION Although this was limited data in CSI patients only, loss to follow-up after 6 months was high. We need to evaluate in all pediatric cancer patients and collaborate to provide financial support, childcare centres for lodging, transportation and health education to promote compliance to follow-up.
Correlation between urine ACR and 24-h proteinuria in a real-world cohort of systemic AL amyloidosis patients
Authors: Alissa Visram, Abdullah S. Al Saleh, Harsh Parmar, Jennifer S. McDonald, John C. Lieske, Iuliana Vaxman, Eli Muchtar, Miriam Hobbs, Amie Fonder, Yi L. Hwa, Francis K. Buadi, David Dingli, Martha Q. Lacy, Angela Dispenzieri, Prashant Kapoor, Suzanne R. Hayman, Rahma Warsame, Taxiarchis V. Kourelis, Mustaqeem Siddiqui, Wilson I. Gonsalves, John A. Lust, Robert A. Kyle, S. Vincent Rajkumar, Morie A. Gertz, Shaji K. Kumar, Nelson Leung
Journal: Blood Cancer Journal (2020)

A 24-h urine protein collection (24hUP), the gold standard for measuring albuminuria in systemic AL amyloidosis, is cumbersome and inaccurate. We retrospectively reviewed 575 patients with systemic AL amyloidosis to assess the correlation between a urine albumin to creatinine ratio (uACR) and the 24hUP. The uACR correlated strongly with 24hUP at diagnosis (Pearson's r = 0.87, 95% CI 0.83-0.90) and during the disease course (Pearson's r = 0.88, 95% CI 0.86-0.90). A uACR ≥300 mg/g estimated a 24hUP ≥ 500 mg with a sensitivity of 92% and specificity of 97% (area under the receiver operating curve = 0.938, 95% CI 0.919-0.957). A uACR cutoff of 3600 mg/g best predicted a 24hUP > 5000 g (sensitivity 93%, specificity 94%), and renal stage at diagnosis was strongly concordant using either 24hUP or uACR as the proteinuria measure (k = 0.823, 95% CI 0.728-0.919). In patients with serial urine collections, a > 30% decrease in uACR predicted a > 30% decrease in 24hUP with a sensitivity of 94%. In conclusion, the uACR is a reliable and convenient method for ruling out proteinuria >500 mg per day, prognosticating renal outcomes, and assessing renal response to therapy. Further studies are needed to validate the uACR cutoffs proposed in this study.
Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development
Authors: Seyed Hossein Kiaie, Mohammad Javad Sanaei, Masoud Heshmati, Zahra Asadzadeh, Iman Azimi, Saleh Hadidi, Reza Jafari, Behzad Baradaran
Journal: Acta Pharmaceutica Sinica B (2020)

Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa.
MBCL-35. SALVAGE RADIATION THERAPY FOR PROGRESSIVE AND/OR RELAPSED PEDIATRIC MEDULLOBLASTOMA
Authors: Muhammad Baig, Mary McAleer, David Grosshans, Arnold Paulino, Patricia Baxter, Murali Chintagumpala, Wafik Zaky, Susan McGovern
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma (MB) has a dismal prognosis after progression or relapse, and there is no standard of care for salvage therapy. Medical records of pediatric patients with progressive/relapsed MB were reviewed for clinical characteristics. We identified 23 patients with recurrent MB with median age at diagnosis of 3.8 years, 14 males (60%). At diagnosis, 16 patients had gross total resection, 1 near total, 5 subtotal, and 1 had biopsy alone. Fifteen patients (66%) had metastatic disease. Tumor histology was classic/nodular in 10, 4 desmoplastic, 8 anaplastic and 1 myogenic. Ten patients (43%) ages &amp;lt; 3 years, were treated with induction chemotherapy followed by high dose chemo and stem cell rescue. Other 13 patients were treated with chemoradiation (11 craniospinal and 2 posterior fossa radiation). Progression free survival after initial treatment was 11 months (range, 3–58 months); 8 patients (34%) had local recurrence, 10 patients (43%) had distant metastasis, 4 patients (17%) had local and distant, and one patient had CSF only recurrence. Salvage therapy was surgery followed by radiation in 12 patients (52%), radiation alone in 3 patients (13%), chemoradiation in 7 patients (30%), and chemotherapy alone in 1 patient. Thirteen patients (56%) received CSI, 6 (26%) received focal and 2 received spinal radiation only. Five year progression free survival and overall survival from the time of relapse were 25% and 45%, respectively. Multidisciplinary care is essential for patients with relapsed MB. Salvage radiation that accounts for the patient’s initial treatment volumes should be considered for these patients.
LGG-17. SYNERGISTIC ACTIVITY OF MAPK INHIBITOR CLASSES REVEALED BY A NOVEL CELL-BASED MAPK ACTIVITY PEDIATRIC LOW-GRADE GLIOMA ASSAY
Authors: Diren Usta, Romain Sigaud, Juliane L Buhl, Florian Selt, Viktoria Marquardt, David Pauck, Stefan Pusch, Jonas Ecker, Thomas Hielscher, Johanna Vollmer, Alexander C Sommerkamp, Tobias Rubner, Darren Hargrave, Cornelis M van Tilburg, Stefan M Pfister, David T W Jones, Marc Remke, Tilman Brummer, Olaf Witt, Till Milde
Journal: Neuro-Oncology (2020)

Abstract Pilocytic astrocytomas (PAs) and other pediatric low-grade gliomas (pLGGs) exhibit aberrant activation of the MAPK signaling pathway caused by genetic alterations, most commonly KIAA1549:BRAF fusions, BRAF V600E and NF1 mutations. In such a single-pathway disease, novel drugs targeting the MAPK pathway (MAPKi) are prime candidates for treatment. We developed an assay suitable for pre-clinical testing of MAPKi in pLGGs, aiming at the identification of novel MAPK pathway suppressing synergistic drug combinations. We generated a reporter plasmid (pDIPZ) expressing destabilized firefly luciferase driven by a MAPK-responsive ELK-1-binding element, packaged in a lentiviral vector system. We stably transfected pediatric glioma cell lines with a BRAF fusion (DKFZ-BT66) and a BRAFV600E mutation (BT-40) background, respectively. Measurement of MAPK pathway activity was performed using the luciferase reporter. pERK protein levels were detected for validation. We performed a screen of a MAPKi library and calculated Combination Indices of selected combinations. The MAPKi library screen revealed MEK inhibitors as the class inhibiting the pathway with the lowest IC50s, followed by ERK and second generation RAF inhibitors. Synergistic effects in both BRAF-fusion and BRAFV600E mutation backgrounds were observed following combination treatments with different MAPKi classes (RAFi/MEKi, &amp;gt; RAFi/ERKi &amp;gt; MEKi/ERKi). We have generated a novel reporter assay for medium- to high-throughput pre-clinical drug testing of MAPKi in pLGG cell lines. MEK, ERK and next-generation RAF inhibitors were confirmed as potential treatment approaches for KIAA1549:BRAF and BRAFV600E mutated pLGGs. Synergistic suppression of MAPK pathway activity upon combination treatments was revealed using our assay in addition.