tbuckley/cabot-search huggingface dataset:
SURG-06. MANAGEMENT OF HYDROCEPHALUS IN ADULT PATIENTS WITH BRAIN METASTASES
Authors: A Vaynerman, L Coombs, H Nickols, R LaRocca, K Sinicrope, D Ishihara, A Spalding, D Sun
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Traditionally patients presenting with hydrocephalus in the setting of brain metastases were associated with poor outcomes. However, in the area of improved systemic therapies, the prognosis of brain metastases has improved, warranting investigation into the management of concomitant hydrocephalus. METHODS We conducted a retrospective review of 12 consecutive patients with brain metastases presenting with hydrocephalus treated with either endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunt (VPS) from June 2013 to December 2018. We then compared our outcomes to 77 historical controls from the literature to test the hypothesis that management of hydrocephalus in patients who respond to systemic therapy is associated with improved outcomes. RESULTS The medial overall survival in our cohort was 182 days compared with 91 days in the reported previous studies, with an odds ratio of 0.5 (95% CI 0.24-1.04). In the 5 patients who underwent ETV, the median survival was 182 days versus 77 days reported in the literature, an odds ratio of 0.42 (95% CI 1.28-1.40). Patients with one brain metastasis did not reach median survival with 4 of 5 patients alive at last follow up, while only 3 of 7 patients with at least two metastases were alive at follow up with a median survival of 182 days. Patients who had immunotherapy were associated with improved survival, while leptomeningeal carcinomatosis still was associated with a negative outcome. CONCLUSIONS Patients with brain metastases and hydrocephalus who underwent neurosurgical CSF diversion had improved survival compared with historical controls, particularly in patients with one metastasis or who received immunotherapy. This study supports initial interdisciplinary evaluation of patients with brain metastases by medical and radiation oncology together with neurosurgery to facilitate immediate systemic therapy after relief of hydrocephalus.
Maternity care: services across England require “immediate and essential actions”
Authors: Clare Dyer
Journal: BMJ (2020)

A catalogue of failures including poor risk assessment, injudicious use of oxytocin, poor monitoring of fetal heart rates, failure to escalate care to more senior clinicians, and a culture of low caesarean rates led to avoidable harm and death for mothers and babies at Shrewsbury and Telford Hospital NHS Trust, a review has concluded.1

The Ockenden review, commissioned by the Department of Health in 2017, called for “immediate and essential actions” to improve safety in all maternity services across England.

The review, which is investigating 1862 maternity cases at the trust, has published its initial findings, covering the first 250 cases reviewed, at the request of health minister Nadine Dorries. She asked for recommendations that could be implemented nationwide after a series of earlier reports highlighted failing maternity services at several NHS trusts.

The recommendations from these reports were “either not implemented or …
QOLP-14. FROM SYMPTOMS TO RADIOTHERAPY: A QUALITATIVE ASSESSMENT OF PATIENT EXPERIENCE IN NEWLY DIAGNOSED HIGH-GRADE GLIOMA
Authors: Jonathan Chainey, Michael Kim, Vivien Ka-Ying Chan, Karolyn Au
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Considering the poor prognosis of high-grade gliomas, past studies focusing on the felt experience and supportive care needs of patients concentrated on the end-of-life period. Little is known on these subjects during the initial acute portion of the patient’s journey, from symptom onset, through surgery, to chemoradiation. This period is one of substantial anxiety for patients and their caregivers, and one during which they struggle to comprehend a large amount of information and navigate a complex situation. METHODS Adult patients with a new histopathological diagnosis of high-grade glioma who underwent radiotherapy participated in a semi-structured, face-to-face interview. Different segments of the patient’s journey were explored, with a focus on patient’s emotions, interactions with healthcare providers, satisfaction during the process and access to supports. Descriptive thematic analysis in the tradition of grounded theory was performed. RESULTS Fifteen patients (7 males, age 34-71 years) were interviewed, and four themes emerged from the analysis. First, information conveyed by the medical team was frequently disconnected from patients’ understanding regarding diagnosis and treatment. Second, specific events created a lasting impression that the medical system, and at times medical care providers, lacked empathy. Third, patients’ perceptions of shortcomings within the medical system led to decreased trust, particularly regarding the follow-up process. Finally, although respondents identified multiple inadequacies during their journey, they nonetheless acknowledged the great support and quality of services they received. CONCLUSION This study provides insight into patients’ experiences and perceived shortcomings of the medical system, from the time of presentation until the end of radiotherapy treatment in patients with new diagnosis of high-grade glioma. These findings should influence clinicians’ attitudes and guide systematic changes including delivery of information and the referral process.
PATH-39. ASSOCIATIONS OF GENOMIC SUBGROUP WITH RECURRENCE IN LOW-GRADE MENINGIOMAS
Authors: Mark Youngblood, Danielle Miyagishima, Lan Jin, Trisha Gupte, Chang Li, Daniel Duran, Julio Montejo, Amy Zhao, Amar Sheth, Evgeniya Tyrtova, Koray Özduman, Francesco Iacoangeli, Matthieu Peyre, Julien Boetto, Matthew Pease, Timuçin Avşar, Anita Huttner, Kaya Bilguvar, Türker Kilic, M Necmettiin Pamir, Nduka Amankulor, Michel Kalamarides, Zeynep Erson-omay, Murat Gunel, Jennifer Moliterno
Journal: Neuro-Oncology (2020)

Abstract Up to 80% of meningiomas are classified as clinically low-grade, however, a subset of these ‘benign’ cases will ultimately recur and require additional treatment. The role of molecular subgroup in meningioma recurrence has not been thoroughly investigated, despite correlations of this variable with other clinical features. Indeed, epigenetic and transcriptional evidence supports involvement of distinct oncogenic processes within each subgroup, and as shown in other brain tumors, this may result in divergent clinical courses. In the present study, we classified 429 meningiomas into six established molecular subgroups based on genomic driver, and investigated associations of each subgroup with tumor recurrence. At two years of follow-up, we observed differences in progression free survival curves among relatively aggressive (NF2-loss, PI3K-activated, Hedgehog-activated) and quiescent (KLF4-mutant, SMARCB1-mutant, POLR2A-mutant) subgroups (log rank p = 4.3 x 10-2), with the former group recurring at a rate 14x higher. We found PI3K-activated meningiomas recurred significantly earlier than other subgroups (average time to recurrence of 19.2 months; p = 2.2 x 10-2), though we observed an intermediate long-term outcome relative to the Hedgehog and NF2 lesions. Overall, Hedgehog tumors recurred significantly more frequently than other low-grade meningiomas (adj. p = 3.1 x 10-2), and this subgroup was found to be an independent predictor of progression free survival using cox proportional hazards modelling (HR = 3.1; p = 2.4 x 10-2). By contrast, the aggressiveness of NF2 meningiomas was found to depend upon gender, WHO grade, and elevated Ki-67 index, and this subgroup was not an independent prognostic predictor. Our results suggest molecular subgroup is predictive of recurrence in low-grade meningiomas, and thus is an important consideration in post-operative management decisions. Routine genotyping to detect Hedgehog and PI3K mutant lesions may identify patients that would benefit from closer follow-up and consideration of adjuvant therapies.
PATH-03. HIGH-GRADE NEUROEPITHELIAL TUMOR SHOWING BCOR IMMUNOPOSITIVITY WITHOUT EXON 15 INTERNAL TANDEM DUPLICATIONS IN A FIVE-YEAR-OLD BOY: A CASE REPORT
Authors: Shogo Wakita, Tomoo Matsutani, Yosuke Watanabe, Seiichiro Hirono, Yoshinori Higuchi, Yasuo Iwadate, Zyunichiro Ikeda, Hideaki Yokoo
Journal: Neuro-Oncology (2020)

Abstract Recent DNA methylation profiling clarified several rare entities of pediatric CNS tumors from institutionally-diagnosed primitive neuroectodermal tumors (PNETs). One of which is CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR), and it carries in-frame internal tandem duplications (ITD) of the BCL6 corepressor (BCOR) in exon 15. In the report, we describe a case of immunohistologically-diagnosed CNS HGNET-BCOR, which lacks exon 15 ITD of BCOR. A five-year-old boy visited a local hospital complaining uncontrolled vomiting for two months, and magnetic resonance imaging (MRI) showed a large well-circumscribed mass in his left cerebellum with ventricular dilatation. He referred to our hospital, and an additional MRI revealed diffuse and weak enhancement of gadolinium and low ADC values in mass. Immediately, he underwent total removal of the tumor and ventricular drainage, and his consciousness recovered soon after surgery. The tumor presented high BCOR expression by IHC, but target PCR did not identify exon 15 ITD of BCOR. As the previously-reported clinical and imaging features of CNS HGNET-BCOR resembled our case, we clinically diagnosed it as a similar phenotype of CNS HGNET-BCOR without exon 15 ITD. He received 60 Gy of extended-local irradiation with concomitant temozolomide and discharged without any neurological deficits. Since BCOR alterations, including ITD, gene fusions, and mutations, play an oncogenic role in several cancers, the present case might harbor another gene aberration of BCOR.
MBRS-54. POOR SURVIVAL IN REPLICATION REPAIR DEFICIENT HYPERMUTANT MEDULLOBLASTOMA AND CNS EMBRYONAL TUMORS: A REPORT FROM THE INTERNATIONAL RRD CONSORTIUM
Authors: Anirban Das, Vanessa Bianchi, Melissa Edwards, Nobish Varghese, Sumedha Sudhaman, Roula Farah, Rina Dvir, Alyssa Reddy, Salmo Raskin, Jordan Hansford, Syed Ahmer Hamid, Saunders Hsu, Lee Yi Yen, Abed Abu Quider, Mithra Ghalibafian, Elisabeth Koustenis, Abeer Al-Battashi, Gary Mason, Joung Lee, Danille Bell, Duncan Stearns, David Ziegler, Michal Zapotocky, Alvaro Lasaletta, Abhaya Kulkarni, Derek S Tsang, Normand Laperriere, Cynthia Hawkins, Eric Bouffet, Vijay Ramaswamy, Uri Tabori
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Mutations in mismatch repair (MMR) and DNA-polymerase (POL) genes lead to DNA replication repair deficiency (RRD), resulting in a growing group of previously under-recognized childhood brain tumors. Medulloblastoma and embryonal tumors are rarely reported in RRD. Their biological and clinical significance is unknown. METHODS We analyzed the clinical and genomic data of embryonal tumors registered in the International RRD Consortium. RESULTS Twenty-six tumors were centrally reviewed to confirm medulloblastoma (n=18), embryonal-tumor, NOS (n=5), and three glioblastoma (excluded). Embryonal tumors were observed at a young age (median: 7-years, IQR: 5;11), and all but one exhibited clinical cues (café-au-lait macules/ family history) of germline RRD. Medulloblastomas with RRD exhibited high-risk features, including anaplastic histology (50%), and SHH-subgroup with TP53-mutation (50%). Importantly, 68% harbored POLE/POLD1 mutations, resulting in median tumor mutation burden of 164 mut/mb. POL-mutated tumors were significantly ultra-hypermutated (&amp;gt;100 mut/mb) than tumors with MMR-deficiency alone (p=0.015). Synchronous and metachronous tumors were observed in 40%. However 90% of the deaths were related to the diagnosis of embryonal CNS tumor. Median survival for the entire cohort was 17-months (95% CI: 10 to 23). Predicted 3-year survival was 37% for medulloblastoma, with no survivors among other embryonal tumors. CONCLUSIONS This is the largest cohort of replication repair deficient medulloblastoma reported till date. The tumors are hypermutated, harbor somatic mutations in TP53 and/or POLE/POLD1, and have very poor survival with current chemo-irradiation based approaches. These biologically unique tumors expand the spectrum of high-risk TP53-mutant SHH-medulloblastoma, and need novel strategies for treatment.
Abstract 17459: Discordance Between Framingham Risk Score and Coronary Artery Calcium in High and Low Risk Populations
Authors: Pawan K Hari, Patrick Antoun, Jeremy Vanthof, Gary P Foster
Journal: Circulation (2012)

OBJECTIVE: To evaluate the discordance between Framingham risk score (FRS) and Coronary Artery Calcium score (CACS) in a high risk population at a tertiary health care center in comparison to the l...
Molecular stratification by BCL2A1 and AIM2 provides additional prognostic value in penile squamous cell carcinoma
Authors: Xingliang Tan, Dong Chen, Shengjie Guo, Yanjun Wang, Yuantao Zou, Zhiming Wu, Fangjian Zhou, Zike Qin, Zhuowei Liu, Yun Cao, Chunhua Lin, Gangjun Yuan, Kai Yao
Journal: Theranostics (2020)

Background: Lymph node metastasis is the most unfavorable prognostic factor of penile squamous cell carcinoma (PSCC). However, patients with the same lymph node status have different outcomes, and molecular classifiers for precise prognostic assessments are lacking. Methods: Comprehensive genomic profiling and high-content proliferation screening were performed in eight PSCC and normal tissue pairs and in cell lines. BCL2A1 and AIM2 were selected and further evaluated by qPCR and Western blot. The clinical relevance and prognostic value of the target genes were validated via immunohistochemistry in a cohort of 220 PSCC patients with a defined pN stage. Finally, the biological functions and molecular mechanisms of BCL2A1 and AIM2 were investigated in vitro and in vivo. Results: BCL2A1 and AIM2 were both upregulated in PSCC tissues and associated mostly with cell proliferation. Staining for either BCL2A1 or AIM2 revealed that both are correlated with pN status, extranodal extension, clinical stage and cancer-specific survival (CSS). Compared to patients who are single-positive or double-negative for BCL2A1 and AIM2, those overexpressing both genes had a higher risk of tumor progression and the poorest survival in the pN0 (5-year CSS: 63.3% vs. 94.9% and 100.0%, respectively, p = 0.000) and pN+ subsets (5-year CSS: 24.1% vs. 45.7% and 55.1%, respectively, p = 0.035). Molecular biofunction and mechanistic studies demonstrated that BCL2A1 and AIM2 knockdown inhibited tumorigenesis via the AIM2/NF-κB/BCL2A1/MAPK/c-Myc signaling pathway. Conclusions: BCL2A1 and AIM2 promote PSCC progression. Integrating BCL2A1 and AIM2 as novel molecular classifiers with pN stage provides additional information for the prognosis and treatment of PSCC patients.
EPCO-07. LEVERAGING TRANSCRIPTOME SEQUENCING AND MATHEMATICAL MODELING TO INVESTIGATE GLIOBLASTOMA-MACROPHAGE INTERACTIONS
Authors: Javier Urcuyo, Andrea Hawkins-Daarud, Susan Massey, Jeffrey Bruce, Peter Canoll, Nhan Tran, Leland Hu, Kristin Swanson
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma (GBM) is the one of the most aggressive and common primary brain malignancies, with a poor median overall survival of less than 15 months. While the immune system is activated and brain-resident microglia and blood-derived macrophages combat the tumor, the tumor can convert some microglia and macrophages to instead exhibit an immune-suppressive phenotype. These co-opted immune cells are thereby termed ‘glioma-associated microglia and macrophages’ (GAMMs), as they allow for continued tumor growth. However, limited clinical data has been collected to understand this phenomenon. As a result, we have collected spatially-distributed image-localized biopsies from a cohort of patients and performed RNA sequencing on each sample. Correlations between normalized RNA counts of genetic markers for macrophages (i.e., CD68, CD163), tumor populations (i.e., SOX2, OLIG2), and key cell functions (i.e., KI67, CASP3) were analyzed. To further investigate the temporal effects that GAMMs have on GBM growth, we proposed the Proliferation-Invasion-Macrophage (PIM) model. This system of partial differential equations incorporates the proliferative and invasive behavior of GBM, as well as populations for both ‘healthy’ and ‘glioma-associated’ macrophages. By exploring the parameter space, we classified the various dynamics of tumor progression and how they relate to the immune response. With further insights of the interactions between GBM and macrophage populations, we can begin to parameterize the model on a patient-specific basis and provide insights to personalized immunotherapies and other novel immune-targeted treatments.
Abstract 10352: Prognostic Value of a New Systemic Nutrition-inflammation Index in Acute Decompensated Heart Failure Patients With Reduced, Mid-range and Preserved Left Ventricular Ejection Fraction
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Jun Nakamura, Makoto Abe, Kyoko Yamamoto, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Yuto Tamura, Takeshi Fujita, Masatake Fukunami
Journal: Circulation (2019)

Backgrounds: Systemic inflammation plays a critical role in the outcomes of heart failure. Malnutrition is also associated with poor outcome in heart failure patients It has been recently reported ...
IMG-13. MRI-BASED RADIOMICS PROGNOSTIC MARKERS OF POSTERIOR FOSSA EPENDYMOMA
Authors: Lydia Tam, Derek Yecies, Michelle Han, Sebastien Toescu, Jason Wright, Kshitij Mankad, Chang Ho, Robert Lober, Samuel Cheshier, Nick Vitanza, Paul Fisher, Darren Hargrave, Tom Jacques, Kristian Aquilina, Gerald Grant, Michael Taylor, Sarah Mattonen, Vijay Ramaswamy, Kristen Yeom
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Posterior fossa ependymomas (PFE) are common pediatric brain tumors often assessed with MRI before surgery. Advanced radiomic analysis show promise in stratifying risk and outcome in other pediatric brain tumors. Here, we extracted high-dimensional MRI features to identify prognostic, image-based, radiomics markers of PFE and compared its performance to clinical variables. METHODS 93 children from five centers (median age=3.3yrs; 59 males; mean PFS=50mos) were included. Tumor volumes were manually contoured on T1-post contrast and T2-weighted MRI for PyRadiomics feature extraction. Features include first-order statistics, size, shape, and texture metrics calculated on the original, log-sigma, and wavelet transformed images. Progression free survival (PFS) served as outcome. 10-fold cross-validation of a LASSO Cox regression was used to predict PFS. Model performance was analyzed and concordance metric (C) was determined using clinical variable (age at diagnosis and sex) only, radiomics only, and radiomics plus clinical variable. RESULTS Six radiomic features were selected (all T1): 1 first-order kurtosis (log-sigma) and 5 texture features (3 wavelet, 2 original). This model demonstrated significantly higher performance than a clinical model alone (C: 0.69 vs 0.58, p&amp;lt;0.001). Adding clinical features to the radiomic features didn’t improve prediction (p=0.67). For patients with molecular subtyping (n=48), adding this feature to the clinical plus radiomics models significantly improved performance over clinical features alone (C = 0.79 vs. 0.66, p=0.02). Further validation and model refinement with additional datasets are ongoing. CONCLUSION Our pilot study shows potential role for MRI-based radiomics and machine learning for PFE risk stratification and as radiographic biomarkers.
EPID-09. QUANTIFYING SOCIAL DETERMINANTS OF HEALTH AMONG GLIOMA PATIENTS
Authors: Angelica Hutchinson, Alexandria Marshall, Fang-Chi Hsu, Kathryn Weaver, Alisha DeTroye, Kristin Strickland Houston, Annette Carter, Michael Chan, Christina Cramer, Adrian Laxton, Stephen Tatter, Glenn Lesser, Mollie Canzona, Roy Strowd
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Social determinants of health (SDH) are modifiable factors that contribute to health outcomes. Despite studies linking SDHs with cervical, ovarian, and prostate cancer outcomes, few studies have explored SDHs in glioma patients. We conducted a cross-sectional survey to characterize and contextualize SDHs in glioma patients by community income, rural/urban residence, and treatment status. METHODS Two validated instruments: PRAPARE (Protocol for responding to and assessing patents’ assets risks and experiences) and AHC (accountable health communities instrument) quantified SDHs; along with study-specific supplemental questions. Risk scores were calculated and combined into an overall and domain-specific (economic, education, neighborhood environment, social context, and healthcare) SDH risk, with a higher score being indicative of higher SDH risk. Scores were compared between low-income (LIC) vs high-income (HIC) communities (defined by median household income), urban vs rural (defined by zip code), and active treatment vs surveillance (determined by patient medical record) using Wilcoxon rank-sum test. RESULTS 100 glioma patients were enrolled: mean age 53 years (range: 22–78); 49% male; 18% oligodendroglioma, 34% diffuse astrocytoma, 38% glioblastoma, 10% other glioma; 68% resided in LICs, 27% in rural zip codes, and 51% were on active treatment. Overall, SDH risk scores were low (mean= 4.43-out-of-38). Scores in the healthcare domain were the highest. Compared to patients from LICs, patients from HICs had higher healthcare risk scores (p&amp;lt; 0.05). Surveillance patients had higher overall SDH risk on the AHC than patients in active treatment (p&amp;lt; 0.05), with age being a confounder. In multivariable analysis, younger age, and astrocytoma histology were associated with higher social health risk. CONCLUSION Glioma patients report relatively few SDH risk factors on standardized instruments designed for general clinic populations. The higher health risk observed in patients in HICs and higher AHC risk for those in surveillance will be further explored in planned qualitative analysis.