tbuckley/cabot-search huggingface dataset:
SCIDOT-06. TOWARDS EXCLUSIVELY LOCAL THERAPY OF GLIOBLASTOMA - ENGINEERING IL-12Fc WITH SUPERIOR TISSUE RETENTION AND MINIMAL SYSTEMIC EXPOSURE AFTER CNS ADMINISTRATION
Authors: Michal Beffinger, Linda Schellhammer, Stanislav Pantelyushin, Iwan Zimmermann, Pascal Egloff, Thorsten Buch, Markus Seeger, Johannes vom Berg
Journal: Neuro-Oncology (2019)

Abstract Intratumoral application of IL-12 overrides the prevailing glioblastoma (GB) associated immunosuppression and can trigger efficient anti-tumor responses. With clinical studies currently testing local expression of IL-12 in brain tumors, concerns on IL-12 systemic toxicity via leakage resurface. The fusion to an immunoglobulin heavy chain constant region (“Fc tag”) should increase tissue retention of IL-12. However, export of IL-12Fc into the blood via the neonatal Fc receptor (FcRn) could nevertheless lead to systemic exposure. Subsequent systemic recycling via FcRn could lead to gradually increasing and eventually toxic serum concentrations. We analysed the effect of the Fc-tag on IL-12 tissue retention and evaluated whether FcRn also is involved in brain export and systemic recycling of IL-12Fc upon local delivery. Human or murine IL-12Fc was delivered in GB-bearing or naïve wt or FcRn-humanized mice (mFcRn-/- hFcRn tg) continuously via mini osmotic pumps or as bolus via convection-enhanced delivery (CED). Brain and blood concentration levels were assessed via ELISA. FcRn affinity of IL-12Fc mutants was assessed via ELISA and surface plasmon resonance. We observed much higher tissue retention of IL-12Fc compared to unmodified IL-12, but also an FcRn-dependent gradual increase of IL-12Fc serum levels. Testing a battery of amino acid substitutions at the FcRn interaction interface, we discovered unique substitutions that largely abolish brain export and systemic accumulation while preserving IL-12Fc functionality, leading to an over 100-fold higher brain to blood ratio than unmodified IL-12. We currently test the impact on efficacy of local IL-12Fc and checkpoint brain tumor treatment in vivo. Achieving high local concentrations at low to absent systemic exposure is an important prerequisite for a large therapeutic window for local treatment of neurologic diseases. The novel Fc-modifications present a promising platform for reducing systemic leakage of Fc-containing therapeutics in the context of continuous or intermittent CNS delivery beyond brain cancer therapy.
SURG-31. SPECTROSCOPIC MRI TO GUIDE BIOPSY OF LOWER GRADE GLIOMAS
Authors: Jeffrey Olson, Brent Weinberg, Saumya Gurbani, Karthik Ramesh, Eduard Schreibmann, Hui-Kuo Shu, Hyunsuk Shim
Journal: Neuro-Oncology (2019)

Abstract Primary brain tumors are serious and life-threatening; thus, accurate histopathologic diagnosis is critical for determining the proper clinical treatment regimen. Grade II/III gliomas (lower grade gliomas, or LGGs), including astrocytomas and oligodendrogliomas, are heterogeneous and potentially contain low- and high-grade areas within the same tumor. Therefore, it is critical to target biopsies to the most aggressive portion of the tumor to avoid tumor under-grading and under-treatment. While glioblastomas are typically targeted based on contrast-enhanced MRI, LGGs have little contrast enhancement to define targets for biopsy treatment guidance. Spectroscopic MRI (sMRI) is a high-resolution MRI imaging method which allows for detection of metabolic abnormalities such as choline and NAA in the entire brain without injection of a contrast agent. We have previously evaluated the relationship between sMRI Cho/NAA ratios and tumor infiltration in surgical specimens from high grade gliomas, demonstrating a strong correlation between sMRI results and glioma infiltration. We also used the location information to correlate sMRI data to genetic and histologic biomarkers (such as 1p19q, IDH, and MGMT). An IRB-approved pilot study to obtain sMRI prior to stereotactic biopsy has been done in 20 non-enhancing LGG cases. Patients with a suspected LGG diagnosis underwent sMRI at the time of their surgical planning MRI. sMRI images were then registered to the T1w-CE and T2/FLAIR images and imported into the Stealth neuronavigation system for biopsy planning. We found that all astrocytomas (regardless of grades) showed strongly elevated Cho/NAA, while the LGGs were hardly delineated on T1w and T2/FLAIR. We found that pathology-confirmed grade II oligodendroglioma do not have choline elevation; however, NAA was mildly decreased, myo-inositol was elevated, and creatine (Cr) was mildly elevated. sMRI is a useful tool to improve biopsy targeting in LGG patients by ensuring that the highest risk regions are sampled.
Prevalence, features and predictive factors of liver nodules in Fontan surgery patients: The VALDIG Fonliver prospective cohort
Authors: Luis Téllez, Enrique Rodríguez de Santiago, Beatriz Minguez, Audrey Payance, Ana Clemente, Anna Baiges, Dalia Morales-Arraez, Vincenzo La Mura, Elba Llop, Elena Garrido, Elvira Garrido-Lestache, Stephanie Tasayco, Onorina Bruno, Raquel Prieto, Silvia Montserrat, Mónica Pons, Andreína Olavarría, Laura Dos, Antoine Legendre, María Jesús del Cerro, Rafael Bañares, Juan Carlos García-Pagán, Pierre-Emmanuel Rautou, Agustín Albillos, Lara Aguilera, Rut Romera, Diego Rincón, María Álvarez Fuente, Xavier Merino, Massimo Chessa, Michela Triolo, Maxime Ronot, Valérie Vilgrain, Antoine Legendre, Caroline Chassing, Virginia Hernández-Gea, Maria Angeles Garcia-Criado, Anna Darnell, Ernest Belmonte, Fanny Turon, Jose Ferrusquia, Marta Magaz
Journal: Journal of Hepatology (2019)
High Risk Genomic Alterations Identified at the Time of Diagnosis Are Strongly Associated with MRD and Subsequent Poor Outcomes in AYA ALL Patients Treated on a Pediatric Inspired Chemotherapy Regimen
Authors: David T Yeung, Matthew Greenwood, Jacqueline Rhen, Susan L Heatley, Barbara McClure, Laura N Eadie, Jimmy Breen, Caitlin Schutz Schutz, Toby N Trahair, Andrew H. Wei, Luciano Dalla-Pozza, Rosemary Sutton, Kenneth F Bradstock, Michael Philip Osborn, Deborah L. White
Journal: Blood (2019)
HOUT-26. FACTORS ASSOCIATED WITH TREATMENT DELAY IN CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Marissa Barbaro, Peter Pan, Sarah Torres, Kiran Thakur, Mary Welch
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVE To identify clinico-radiographic characteristics associated with delayed treatment initiation in central nervous system lymphoma (CNSL). INTRODUCTION Clinical and radiographic characteristics of CNSL are often varied with a broad differential diagnosis, potentially leading to delays in diagnosis and treatment. METHODS A single-center retrospective review of clinico-radiographic data was performed at Columbia University Irving Medical Center in patients with pathologically confirmed CNSL diagnosed from 1/2010–12/2018. Descriptive statistics and univariate logistic regression were used to identify variables associated with delayed treatment. Using visual binning, delayed treatment time was designated as &gt;33 days from first presentation to medical attention to first chemotherapy for CNSL. Variables of interest included demographic data, presenting symptomatology, radiographic characteristics, location of initial presentation, and diagnostic and therapeutic interventions performed before biopsy. RESULTS Seventy patients (36 men (51%); median age at diagnosis 70 years, IQR 14.75 years; median time from first presentation to treatment 21 days, IQR 41.25 days) were included. Presentation with cognitive deficits suggested a strong, but not statistically significant, association with delayed treatment (OR=1.93, p=0.20), whereas presentation with focal neurologic deficits suggested protection against delayed treatment (OR=0.25, p=0.05). Initial presentation to a hospital suggested a strong, but not statistically significant, trend against delayed treatment (OR=0.41, p=0.08). Multifocal disease on neuroimaging (OR=7.18, p=0.001), pre-biopsy cerebrospinal fluid (CSF) sampling (OR=5.18, p=0.002), and pre-biopsy immunomodulatory treatment (including high-dose intravenous corticosteroids) for suspected neuroinflammatory disease (OR=6.33, p=0.03) had statistically significant associations with delayed treatment. Antimicrobial treatment before biopsy for suspected CNS infection suggested a trend toward delayed treatment, but the association was not statistically significant (OR=5.1, p=0.06). CONCLUSIONS Multifocal disease and pre-biopsy CSF sampling and immunomodulatory therapy were associated with delayed treatment initiation for CNSL in our single-center cohort. Recognizing factors associated with delayed treatment may allow physicians to circumvent these factors and permit more rapid diagnosis through tissue sampling.
Persistent Leukocytosis in Polycythemia Vera Is Associated with Disease Evolution but Not Thrombosis: An Analysis from a 520-Patient Retrospective Multi-Center Database
Authors: Lukas Ronner, Nikolai A. Podoltsev, Jason Gotlib, Mark L Heaney, Andrew T Kuykendall, Casey L. O'Connell, Jamile M. Shammo, Angela G. Fleischman, Robyn M. Scherber, Ruben A. Mesa, Abdulraheem Yacoub, Douglas Tremblay, Kimia Ziadkhanpour, Cecelia Perkins, Shelby Meckstroth, Lindsey Behlman, Matthew Chiaramonte, Ronald Hoffman, Erin Moshier, John Mascarenhas
Journal: Blood (2019)
Sulthiame Treatment of Epilepsy
Authors: H. G. Garland, D. W. Sumner
Journal: BMJ (1964)

This study assessed performance on a screening test of competency to consent to treatment, the Hopkins Competency Assessment Test (HCAT), in a population diagnosed with chronic mental illness, and examined the relationship between HCAT performance and functional status at discharge. We hypothesized that patients with chronic mental illness who failed the HCAT would also have problems in performing activities of daily living at the time of discharge. Forty-three patients on a short-stay psychiatric service were administered the following screening tests: (1) Mini-Mental State Exam (MMSE), on admission; (2) the HCAT, approximately four to five days after admission; (3) At discharge, the Milwaukee Evaluation of Daily Living Skills (MEDLS), and the Occupational Therapy Task Observation Scale (OTTOS). Analyses included correlation between the competency measure HCAT and the functional measures; sensitivity, specificity, and positive and negative predictive values of the HCAT score; and odds ratio and chi-square analysis. The HCAT was highly correlated with the MEDLS and OTTOS. The HCAT was not sensitive in identifying impairment on either functional measure, but when patients failed the HCAT, they were likely to be functionally impaired at discharge. The negative predictive value of the HCAT was greater than the positive predictive value. Patients who failed HCAT were significantly more likely to have an MMSE score lower than 27 and less than 12 years of school. Seven of forty-three (16.3%) patients failed a screening measure of competency, indicating that there is a subgroup of chronically mentally ill patients who may not understand issues of informed consent. Patients who failed the HCAT were more likely to be functionally impaired at discharge. Cognitive impairment and low education are important factors in failure to pass competency screening. Competency screening along with screening for cognitive impairment can be useful in identifying patients at risk for poor functional status at discharge.
A Phase II Single-Arm Open-Labeled Study Evaluating Combination of Quizartinib and Omacetaxine Mepesuccinate (QUIZOM) in Newly Diagnosed or Relapsed/Refractory AML Carrying FlT3-ITD
Authors: Chunxiao Zhang, Garret MK Leung, Sze Pui Tsui, Ho-Wan Ip, Edmond S. K. Ma, Chun Hang Au, Chris T.L. Chan, Ka Lam Nelson Ng, Sze Fai Yip, Bonnie Kho, Harold K K Lee, Qing LIU, Thomas Wing Yan Leung, Yok Lam Kwong, Anskar Yu Hung Leung
Journal: Blood (2019)
Interactions between Donor Activating Killer Immunoglobulin-like Receptors (KIRs) and Somatic Mutations and Their Association with Outcomes after Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia (AML)
Authors: Sanghee Hong, Lisa Rybicki, Aiwen Zhang, Dawn Thomas, Cassandra M Kerr, Donna Corrigan, Arden Emrick, Hetty E. Carraway, Aziz Nazha, Sudipto Mukherjee, Anjali S. Advani, Matt Kalaycio, Brian J. Bolwell, Rabi Hanna, Aaron T. Gerds, Brad Pohlman, Betty K. Hamilton, Mikkael A. Sekeres, Navneet S. Majhail, Jaroslaw P. Maciejewski, Medhat Askar, Ronald Sobecks
Journal: Blood (2019)
Therapy-Related Myeloid Neoplasms Following Treatment for Multiple Myeloma : A Single-Center Analysis
Authors: Amelie Boquoi, Soraya Magdalena Banahan, Judith Strapatsas, David Lopez y Niedenhoff, Guido Kobbe, Norbert Gattermann, Ulrich Germing, Rainer Haas, Thomas Schroeder, Roland Fenk
Journal: Blood (2019)
RTHP-06. IMPACT OF THE AMERICAN TAX PAYER RELIEF ACT ON STEREOTACTIC RADIOSURGERY UTILIZATION IN THE UNITED STATES
Authors: Shearwood McClelland III, Catherine Degnin, Yiyi Chen, Gordon Watson, Jerry Jaboin
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION For brain metastases, single-fraction stereotactic radiosurgery (SRS) spares appropriately chosen patients from the invasiveness of operative intervention and the permanent cognitive morbidity of whole brain radiation. SRS is delivered predominantly via two modalities: Gamma Knife, and linear accelerator (LINAC). The implementation of the American Tax Payer Relief Act (ATRA) in 2013 represented the first time limitations specifically targeting SRS reimbursement were introduced into federal law. The subsequent impact of the ATRA on SRS utilization in the United States (US) has yet to be examined. METHODS The National Cancer Data Base (NCDB) from 2010–2016 identified brain metastases patients from non-small cell lung cancer (NSCLC) throughout the US having undergone SRS. Utilization between GKRS and LINAC was assessed before (2010–2012) versus after (2013–2016) ATRA implementation. Utilization was adjusted for several variables, including patient demographics and healthcare system characteristics. RESULTS From 2012 to 2013, there was a substantial decrease of LINAC SRS in favor of GKRS overall (37% to 28%) and individually in both academic and non-academic centers. Over the three-year span immediately preceding ATRA implementation, 65.8% received GKRS and the remaining 34.2% receiving LINAC. In the four years immediately following ATRA implementation 68.0% received GKRS compared with 32% receiving LINAC; these differences were not statistically significant. CONCLUSIONS ATRA implementation in 2013 caused an initial spike in Gamma Knife SRS utilization, followed by a steady decline, similar to rates prior to implementation. These findings are indicative that the ATRA provision mandating Medicare reduction of outpatient payment rates for Gamma Knife to be equivalent with those of LINAC SRS had a significant short-term impact on the radiosurgical treatment of metastatic brain disease throughout the US. Such findings should serve as a reminder of the importance and impact of public policy on treatment modality utilization by physicians and hospitals.
Neurofilament light chain is a promising serum biomarker in spinocerebellar ataxia type 3
Authors: Quan-Fu Li, Yi Dong, Lu Yang, Juan-Juan Xie, Yin Ma, Yi-Chu Du, Hao-Ling Cheng, Wang Ni, Zhi-Ying Wu
Journal: Molecular Neurodegeneration (2019)

Abstract Background Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression or therapeutic response. Neurofilament light chain (NfL) was recently proposed as a serum biomarker for many neurodegenerative disorders. The present study investigated whether NfL was a promising serum biomarker for SCA3. Methods Seventeen SCA3 patients and 9 controls were enrolled in cohort A, and 116 SCA3 individuals (preclinical and patients) and 91 controls were recruited as cohort B. We assessed whether serum NfL correlated with cerebrospinal fluid (CSF) NfL in cohort A and correlations between serum NfL levels and clinical features and brain volumes were determined in cohort B. The single-molecule array method was used to measure serum NfL levels. Disease severity was determined using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). Cerebellar and brainstem volumes were assessed using MRI neuroimaging measurements. Results Serum/CSF NfL levels in cohort A were elevated in SCA3 patients, and serum and CSF NfL exhibited a significant positive correlation ( r = 0.9179, p &lt; 0.0001). Levels of serum NfL in cohort B were significantly higher in preclinical SCA3 (15.03 ± 7.49 vs 6.88 ± 2.72 pg/ mL, p &lt; 0.0001) and manifest SCA3 subjects (37.56 ± 13.47 vs 9.07 ± 6.02 pg/ mL, p &lt; 0.0001) compared to those in controls. Serum NfL concentrations increased from early disease stage to the next stage. Levels of serum NfL in ATXN3 mutation carriers were positively associated with SARA ( r = 0.5458, p &lt; 0.0001) and ICARS scores ( r = 0.5522, p &lt; 0.0001). Significant negative associations with cerebellar volumes ( r = − 0.4217, p = 0.0003) and brainstem volumes ( r = − 0.4263, p = 0.0003) were observed. All changes remained significant after adjustment for age and CAG repeat. Conclusions Levels of serum NfL were significantly elevated in SCA3 individuals and correlated with disease severity. Serum NfL is a promising serum biomarker of disease onset and progression, and a potential candidate biomarker of treatment response in SCA3.
Accrual Barriers and Detection of Early Toxicity Signal in Older Less-Fit Patients Treated with Azacitidine and Nivolumab for Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS) in the SWOG 1612 Platform Randomized Phase II/III Clinical Trial
Authors: Annette E. Hay, Sarit Assouline, Roland B. Walter, Richard F. Little, Anna Moseley, Sperling M Gail, Annie Im, James M. Foran, Jerald P. Radich, Min Fang, Megan Othus, Harry P. Erba, Laura C. Michaelis
Journal: Blood (2019)
CMET-38. PREVALENCE AND SURVIVAL OUTCOMES OF UROTHELIAL CARCINOMA BRAIN METASTASES
Authors: Vasileios Kavouridis, Maya Harary, Timothy Smith, David Braun, Bryan Iorgulescu
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Urothelial carcinoma is a common malignancy with ~79,000 new cases diagnosed annually. However, urothelial brain metastases (UBM) are encountered uncommonly. Herein we evaluate their national prevalence, predictors, and treatment outcomes in the contemporary era. METHODS The characteristics, management, and overall survival (OS) of UBM patients (2010–2015) were evaluated using the National Cancer Database, which comprises &gt;70% of all newly diagnosed cancers in the U.S. OS was analyzed with Kaplan-Meier methods and log-rank tests. National outcomes were compared to our institutional cohort of UBMs. RESULTS Out of 208,600 patients diagnosed with urothelial carcinoma, 8.4% presented with stage IV disease--of these only 216 (1.2%) had BMs at the time of diagnosis. Patients presenting with bone, liver, or lung metastases were more likely to present with synchronous BMs. Brain involvement demonstrated significantly worse median OS (3.9mos, 95%CI: 3.1–4.9) than non-BM stage IV disease (10.9mos, 95%CI: 10.6–11.2, p&lt; 0.001). Compared to non-BM stage IV disease, UBMs were more likely to have surgery for metastatic disease and receive radiotherapy (p&lt; 0.001); but were less likely to have primary resection or chemotherapy. In multivariable analysis of stage IV urothelial cancer, BMs demonstrated significantly worse OS (HR 1.43, 95%CI: 1.20–1.72, p&lt; 0.001). In our institutional data, 10 urothelial cancer patients developed BMs; of which 7 were male, median age and KPS at diagnosis were 64.9yo (IQR 56.4–72.0) and 85 (IQR 75–100). Four patients had synchronous metastases; the median number of BM lesions was 2 (IQR 1–2), with a median size of 2.6cm (IQR 1.6–3.3). All 10 underwent GTR, 3 also with SRS and 7 with WBRT, associated with a median OS of 16.5mos. CONCLUSIONS Our results confirm the rarity of UBMs and suggest that BM screening may only be indicated in stage IV patients with neurological symptoms. Systemic therapies demonstrate improved OS in these patients.
Women’s Roles and Barriers to Leadership in the National Collegiate Athletic Association
Authors: Ann M. Sheehy, Peter Miller, Molly Carnes
Journal: JAMA Internal Medicine (2019)

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QOLP-20. IMPACT OF GLIOBLASTOMA ON PATIENT-REPORTED SYMPTOM BURDEN AND PHYSICAL ACTIVITY ASSESSED BY CONVENTIONAL INSTRUMENTS AND A NOVEL DEVICE–BASED TECHNOLOGY
Authors: Terri Armstrong, Vinay Puduvalli, Tobias Walbert, Katherine Peters, Ashlee Loughan, Manmeet Ahluwalia, Paula Province Warren, David Cachia, Jennie Taylor, Jaishri O Blakeley, Arijit Ganguli, Nikhil Khandelwal, Rajesh Kamalakar, Les Noe, Priya Kumthekar
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is a rapidly progressing disease associated with significant deterioration in quality of life. This study evaluated clinical patient-reported outcomes (PROs) and the physical activity of patients with GBM. Adults with GBM (n=180) were stratified across 4 groups representing specific stages in the disease course: Group 1=newly diagnosed; 2=postradiation; 3=stable disease; 4=recurrence. Self-reported physical function (EORTC-QLQC30), motor dysfunction (BN20), symptom burden and interference (MDASI-BT), and objective physical activity level (via Fitbit®) were compared across groups by ANOVA. Associations between outcomes were assessed with a Pearson correlation (r) test. Patients were highly symptomatic, with overall mean (MDASI-BT) symptom severity (1.7–2.4; P=0.23) and interference (2.3–3.2; P=0.68) scores similar across groups. Patients with recurrent disease experienced the numerically greatest symptom severity and interference. Self-reported activity-related interference scores (2.7–3.6, P=0.48) were highest in patients with newly diagnosed or recurrent disease. Motor dysfunction (BN20) mean scores were highest in postradiation (22) and recurrent (22) disease groups (P=0.95). Mean physical function (EORTC-QLQC30) scores were worse in patients with recurrent disease (67) than in those with stable disease (79; P=0.38). Newly diagnosed patients and those with stable disease were the most active (≈4000 and ≈4500 mean steps/day, respectively), whereas those with recurrent disease were least active (≈2300 mean steps/day; P=0.032). Greater physical activity (via Fitbit®) correlated with better self-reported physical function (EORTC-QLQC30) for all groups (Group 1, r=0.0292; Group 2, r=0.0211; Group 3, r=0.0008; Group 4, r=0.0002). Greater motor dysfunction was correlated with lower physical activity in patients with stable (r=0.0003) and recurrent (r=0.0441) disease. Patients in this study were highly symptomatic throughout the disease stages with disease recurrence associated with worse motor and physical function. Future studies exploring these findings in a longitudinal cohort are needed to assess this relationship.