bluuebunny/crossref_metadata_2025_split huggingface dataset:
EOLP-03. A RETROSPECTIVE STUDY ON CAUSE OF DEATH DUE TO HIGH-GRADE GLIOMAS IN PEDIATRIC VERSUS ADULT PATIENTS
Authors: Franson Andrea , Junck Larry , Lyons Samantha 
Published: November 2022

Abstract

BACKGROUND
Limited literature exists on the presumed pathophysiologic mechanisms by which children, adolescents and adults die from high-grade gliomas (HGGs). This study aims to identify the likely specific cause of death in patients with HGG based on imaging review in proximity to death. A secondary aim is to assess the use and timing of palliative care/hospice in patients with HGG. We hypothesized that most patients with HGG, both adult and pediatric, die from primary neurologic failure as a result of local tumor progression, with additional causes including hydrocephalus with subsequent brainstem herniation or causes indirectly related to tumor progression such as systemic infection.

METHODS
We conducted a retrospective review of pediatric patients with WHO Grade 4 gliomas and adults with de novo Grade 3 or 4 gliomas or Grade 2 glial tumors that transformed to Grade 3/4, diagnosed from 2016 to 2021 at Michigan Medicine (IRB exemption obtained). We reviewed imaging and clinical records of patients who had brain MR and/or CT imaging within 3 - 6 weeks of death to determine a likely cause of death.

RESULTS
Twenty-six pediatric patients and 43 adult patients identified met inclusion criteria. Initial analysis reveals that the majority of patients with HGG died from local tumor progression and subsequent neurologic failure. We also noted a greater use of palliative care/hospice services in pediatric patients, with less frequent referral for adult patients at any time in their disease course. Pediatric patients are almost always supported by Child and Family Life, while psychological services are rarely received by adult patients.

CONCLUSIONS
Analysis is ongoing, though trends indicate that the primary cause of death in patients with HGG is through primary neurologic failure, and that there may be opportunities to lessen end-of-life suffering through patient education and the use of support services.
EPID-02. ANTIBODY REACTIVITY TO VARICELLA-ZOSTER VIRUS AND THREE OTHER HERPESVIRUSES AND SURVIVAL IN ADULTS WITH GLIOMA
Authors: Guerra Geno , Francis Stephen , McCoy Lucie , Hansen Helen , Rice Terri , Molinaro Annette , Wiencke John , Wrensch Margaret 
Published: November 2022

Abstract

Measures of Varicella-Zoster virus (VZV) have been consistently inversely associated with glioma risk, but the association with glioma survival has not been investigated. In this study we analyzed overall survival of individuals with glioma in relation to measured levels of antibodies to 4 common viral infections, measured post-diagnosis.

METHODS
We utilized immunoglobulin G (IgG) antibody measurements to VZV, Epstein-Barr virus (EBV), herpes simplex virus (HSV), and cytomegalovirus (CMV), collected from 1378 patients newly enrolled in the UCSF Adult Glioma Study between 1991-2010. Blood was obtained a median of 3 months post diagnostic surgery. Subject follow-up for survival is ongoing. The associations of IgG levels with overall survival were estimated using Cox models adjusted for age, sex, race, type of surgery, dexamethasone usage, and stratified by tumor grade.

RESULTS
The 1378 glioma patients studied had median survival of 2.1 years. VZV antibody seropositivity was associated with improved survival outcomes (Hazard ratio, HR = 0.70, 95% Confidence Interval 0.54-0.90, p = 0.0061), with a grade-IV specific association (HR=0.65, 0.48-0.87, p=0.0046). Amongst VZV seropositive cases, those in the bottom quartile of measured seroreactivity had significantly worse survival outcomes as compared to the upper three quartiles (HR = 1.31, 1.13-1.52, p = 0.0003). Antibody seropositivity to EBV was also associated with improved survival times (HR = 0.71, 0.53-0.96, p = 0.028). Antibody response to two other common viruses (CMV, HSV) were not associated with glioma survival (p = 0.213, p = 0.215, respectively).

CONCLUSION
This is the first study, to our knowledge, to associate virus-specific antibody levels with survival amongst glioma patients. These associations do not appear to be due to general tumor-induce immune suppression. Our results controlled for dexamethasone usage, a known immunosuppressor. IgG measurements were taken post-glioma diagnosis, therefore further study is needed to determine the direction of causation, and if anti-herpesvirus treatment, such as VZV vaccination, might be beneficial for glioma prognosis.
EPID-03. PATHOGENIC GERMLINE MUTATIONS IN GLIOMA PATIENTS
Authors: Mandel Jacob , Jalali Ali , Patel Akash , McDonald Malcolm , Prather Lyndsey , Helfer Cassandra , Gu Xiangjun , Ludmir Ethan , Echeverria A J , Rao Ganesh , Dhar Shweta , Amos Chris 
Published: November 2022

Abstract

BACKGROUND
No consensus germline testing guidelines currently exist for glioma patients. Hence such testing is not routinely performed. The prevalence and type of germline pathogenic variants in these brain tumors remains unknown. DESIGN/

METHODS
A retrospective review of patients treated at Baylor College of Medicine with paired tumor/normal sequencing using the Tempus xT tumor/normal matched approach from August 2018- April 2022 was performed. Corresponding clinical data was collected for these patients.

RESULTS
We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wildtype, 3/42 (7.1%) of Astrocytoma, IDH mutant and 1/26 (3.8%) of Oligodendroglioma, IDH mutant and 1p/19q co-deleted patients. Pathogenic variants in BRCA2, MUTYH and CHEK2 were seen more commonly (3/15 or 20% each). BRCA1 variants were seen in 2/15 (13%) patients, with variants in NF1, ATM, MSH2, and MSH3 occurring in one patient (7%) each. Second hit somatic variants were seen in 3/15 patients (20%). A second somatic hit was seen in NF1, MUTYH and MSH2 in one patient (7%) each. Referral to genetics was performed in 6/15 (40%) patients with pathogenic germline variants. Median overall survival was 1.6 years for glioblastoma, IDH wildtype patients with a pathogenic germline variant compared to 1.79 years for glioblastoma, IDH wildtype patients without it (p = 0.67).

CONCLUSIONS
Although not routinely performed in glioma patients, pathogenic germline variants occurred in ~10% of our patients. Only 40% of these patients were referred to genetics. These findings suggest a possible overlooked opportunity for determination of hereditary cancer syndromes with impact on surveillance as well as potential broader treatment options. Further research to confirm the occurrence and types of pathogenic germline variants in patients with IDH wildtype compared to IDH mutant tumors is necessary.
EPID-04. IMPACT OF SEX DIFFERENCES IN IRON SUPPLEMENTATION AND OUTCOMES IN ANEMIC GLIOBLASTOMA PATIENTS
Authors: Shenoy Ganesh , Khunsriraksakul Chachrit , Palsa Kondaiah , Khristov Vladimir , Lathia Justin , Barnholtz-Sloan Jill , Connor James 
Published: November 2022

Abstract
We performed a retrospective sex-stratified analysis on 1750 histologically confirmed surgical glioblastoma patients (737 female, 1013 male) diagnosed between January 1, 2000 – January 1, 2020 in the TriNetX Research Network. Among 737 female glioblastoma patients, 140 (18.99%) were classified as anemic (defined as having mean 5-year-post-diagnosis hemoglobin levels &lt; 12 g/dL). Among 1013 male patients, 177 (17.4%) were classified as anemic (mean 5-year-post-diagnosis hemoglobin levels &lt; 13 g/dL). Of the 140 anemic female patients, 30 (21.4%) received iron supplementation whereas 28 (15.8%) of 177 anemic male patients received iron supplementation. Anemic female patients receiving iron supplementation were on average younger than anemic female patients who did not receive supplementation (mean age at diagnosis (SD): 59.08 vs. 64.87, p = 0.037), however no statistically significant differences in presence of chemotherapy administration, radiation administration, or Charlson comorbidity index (CCI) were detected. Anemic male patients receiving iron supplementation had no significant difference in mean age at diagnosis, chemotherapy administration, radiation administration, or CCI compared to anemic male patients not receiving iron supplementation. Kaplan-Meier analysis revealed that iron supplementation in anemic female patients was associated with prolonged overall median survival (536 vs. 361 days, p = 0.03) whereas iron supplementation in anemic male patients was not associated with any significant increase in overall survival (392 vs. 361 days, p = 0.89). Multivariate analysis using a Cox proportional hazards model adjusted for mean 5-year-post-diagnosis hemoglobin levels, age at diagnosis, chemotherapy administration, radiation administration, and CCI revealed that iron supplementation was associated with improved survival in anemic female patients (HR: 0.53, 95% CI: 0.30 – 0.96) but not in anemic male patients (HR: 0.87, 95% CI: 0.54 – 1.43). These results highlight the importance of iron biology in glioblastoma and provide evidence for further investigation into iron supplementation of anemic glioblastoma patients.
EPID-05. LEPTOMENINGEAL METASTASES IN GLIOMA REVISITED: HIGH INCIDENCE AND THEIR MOLECULAR PREDICTORS BASED ON RECENT IMAGING AND MOLECULAR DIAGNOSTICS
Authors: Park Yae Won , Ahn Sung Soo , Chang Jong Hee , Kim Se Hoon , Lee Seung-Koo 
Published: November 2022

Abstract

BACKGROUND
Leptomeningeal metastases (LM) in glioma has been underestimated due to low incidence and lack of reliable imaging. This study aimed to investigate a real-world incidence of LM using a CSF-sensitive MR imaging technique and analyze molecular predictors for LM in the molecular era.

METHODS
Total 1,405 adult glioma patients underwent post-contrast fluid attenuated inversion recovery (FLAIR) imaging at initial diagnosis and during treatment monitoring between March 2001 and October 2021. Molecular data included isocitrate dehydrogenase (IDH) mutation, 1p/19q co-deletion, H3 K27M alteration, and O6-methylguanine-methyltransferase (MGMT) promoter methylation status. Multivariable logistic regression analysis for LM development was performed in molecular data, clinical data, and imaging characteristics. Median overall survival (OS) was compared between patients with and without LM using Kaplan-Meier survival curves and log-rank test.

RESULTS
LM was identified in 16.2% of glioma (228 of 1405), with 7.8% (110 of 1405) at initial diagnosis, and 8.4% (118 of 1405) at recurrence. Among molecular diagnostics, IDH-wildtype (odds ratio [OR] 3.14, P = .001) and MGMT promoter unmethylation (OR 1.43, P = .034) were independent predictors of LM. WHO grade 4 (OR 10.52, P &lt; .001) and nonlobar location (OR 1.54, P =.048) were associated with LM at initial diagnosis, whereas IDH-wildtype (OR 5.04, P &lt; .001) and H3 K27M alteration (OR 3.39, P =.003) were significantly associated with LM at recurrence. Patients with LM had a worse median OS than those without LM (16.7 vs. 32.0 months, log-rank test; P &lt; .001).

CONCLUSIONS
CSF-sensitive MR imaging diagnostics aid diagnosis of LM and reduced an underdiagnosed condition in adult gliomas. Molecular markers affect LM at initial diagnosis and at recurrence, and patients with aggressive molecular markers warrant imaging surveillance of LM.
EPID-09. AGE-STRATIFIED SURVIVAL ANALYSES OF CO-MORBIDITIES IN PATIENTS WITH GRADE IV GLIOMAS
Authors: Rabin Erik , Mi Xinlei , Huang Jonathan , Kim Miri , Mozny Andreas , Amidei Christina , Sieg Erica , Bell April , Zhai Lijie , Bommi Prashant , Lauing Kristen , Lukas Rimas , Wainwright Derek 
Published: November 2022

Abstract
Glioblastomas are the most common primary malignant brain tumor in adults. Subject age is a strong prognostic factor for survival. We performed a co-morbidity analysis of younger vs. older (greater than 65 years) adults with grade IV gliomas (GIV) to understand inherent differences that vary with subject age. Electronic health records for 1,208 GIV patients were collected at a single center between 1/1/2000 and 9/8/2021 and used to construct a multivariable time-dependent cox model that examined intra-cohort hazards associated with 33 measures of co-morbidity and tumor related symptoms. The date of GIV diagnosis was identified as the start time, and subject death was used to define event time. Patients that were alive or lost to follow-up were censored at the last recorded date. Survival time was calculated as the difference between diagnosis date and event time or censorship. GIV was stratified by IDH and MGMT promoter methylation status when available. Younger patients experienced a greater hazard with: limitations to movement (1.88 [1.46, 2.43] ****), gait (1.72 [1.17, 2.52] **), weakness (1.96 [1.26, 3.06] **), seizures (1.28 [1.04, 1.58] *), epilepsy (1.47 [1.09, 1.99] *), and anxiety disorders (2.37 [1.44, 3.92], **). Older GIV patients experienced an increased hazard with: confusion and altered mental status (4.3 [2.08, 8.89], ****). Both age groups experienced increases with eye/visual systems and plegia. These data indicate novel comorbid enrichments varying by subject age that, from a mechanistic perspective, may be used to better understand why older adults with GIV survive significantly less than younger counterparts.
EPID-12. REGIONAL VARIATIONS IN THE INCIDENCE OF BRAIN GLIOMA IN ADULTS IN ALABAMA
Authors: Lobbous Mina , Abdelrashid Moaaz , Estevez-Ordonez Dagoberto , Markert James , Tipre Meghan , Brown Elizabeth , Nabors Louis , Lewis Cora 
Published: November 2022

Abstract

BACKGROUND
Gliomas are the most common primary brain tumor in adults in the US with an annual age-adjusted incidence rate (AAA-IR) of 4.67 to 5.73 per 100,000 persons. There are several sources of carcinogenic contaminants in northeast Alabama and western Georgia with the Coosa River serving as the region’s primary water source. We aimed to examine the incidence rate of glioma, as well as tumor characteristics and overall survival, in northeast Alabama compared to the rest of the state.

METHODS
This is a retrospective cohort study using the UAB Neuro-Oncology clinic database including adult patients ( ≥ 20 years at diagnosis) with histologically confirmed diagnosis of glioma (ICD10: 71.9) residing in the state of Alabama at the time of diagnosis between January 2015 and December 2019. We calculated AAA-IR among residents in counties intersected by the Coosa River in northeast Alabama (exposed group) compared to the rest of the state (non-exposed group). The electronic medical records of the participants were reviewed for patient demographics, insurance status, tumor grade and molecular markers, as well as the vital status. The overall survival was graphically examined using Kaplan-Meier.

RESULTS
A total of 660 patients were included in this study (528 non-exposed, and 132 exposed). The AAA-IR of glioma in the exposed group was 4.76 per 100,000 persons vs 3.14 per 100,000 persons in the non-exposed group with a 50 % higher incidence rate of glioma in the exposed group (RR = 1.50; 95% CI, 1.22-1.89). There was no statistically significant difference between the two groups with respect to age at diagnosis, sex, race, surgery type, tumor grade, IDH status, or overall survival.

CONCLUSIONS
Our findings indicate a higher incidence of glioma in northeast Alabama. Future geospatial and population-based epidemiological investigations are needed to identify possible regional environmental risk factors and examine temporal sequence.
EPID-14. EPIDEMIOLOGICAL SURVEY OF RADIATION-INDUCED MENINGIOMA: A SEER ANALYSIS
Authors: Abaricia Jefferson , Matharoo Jashanjeet , Opalak Charles , Broaddus William 
Published: November 2022

Abstract

OBJECTIVE
Radiation-induced meningioma (RIM) is a rare but serious consequence of cranial and cranio-spinal external beam radiation therapy (EBRT). While recent studies have characterized the epidemiological features of RIM in small populations or systematic reviews, none have studied RIM within a national database for a more generalizable description of this disease entity. The objective of this study was to identify and characterize the population with RIMs within a large national database.

METHODS
From the SEER Research Plus Nov 2020 (1975-2018) dataset, 56161 patients treated with EBRT for the following indications were identified: ocular/orbital tumors, brain/nervous system tumors, and leukemias. Next, a sub-population of 185 RIM patients, defined by histologically distinct precedent tumor treated with EBRT and a minimum 5-year latency from EBRT to meningioma, was identified. RIM prevalence, latency, pathologic behavior, and multiplicity were determined, and comparisons were made by sex, race, and original indication for EBRT.

RESULTS
The prevalence of RIM among the EBRT population was 0.33%. Among RIM patients, 41.62% were male and 84.32% were Caucasian. Average latency to RIM development was 23.39 ± 8.65 years, with no significant difference between sexes or races. Fourteen patients had multiple RIMs at diagnosis, while four patients experienced recurrent RIM. RIMs classified as “malignant” had a shorter latency (16.30 years) than “borderline” (26.11 years) or “benign” (23.36 years) RIMs. Of the most common original EBRT indications, precursor lymphoblastic leukemia (29.89 years) had longer latency to RIM than medulloblastoma (21.57 years) or astrocytoma (22.67 years); this may be explained by lower doses of radiation used for lymphoblastic leukemia treatment.

CONCLUSION
These data provide novel epidemiological information—most importantly, prevalence—of RIM in a nationwide population, and they suggest that RIM occurs in patients independent of sex or race. These findings will aid clinicians in explaining the risk of RIM development to patients undergoing EBRT.
EPID-18. IATROGENIC IMMUNODEFICIENCY ASSOCIATED LYMPHOPROLIFERATIVE DISORDERS OF THE CENTRAL NERVOUS SYSTEM: A TREATMENT PARADOX
Authors: Tadipatri Ramya , Ekhator Chukwuyem , Narayan Ram , Azadi Amir , Yuen Kevin , Grewal Jai , Fonkem Ekokobe 
Published: November 2022

Abstract

BACKGROUND
Primary central nervous system lymphomas (PCNSLs) have historically had dismal survival rates until the advent of high-dose methotrexate (HD-MTX) based chemotherapy regimens. With increasing prevalence of autoimmune disease and development of new immunosuppressants, a genetically distinct entity known as iatrogenic immunodeficiency associated lymphoproliferative disorder (LPD) has emerged. Many of these cases arise following methotrexate use, challenging feasibility of standard HD-MTX regimens. The aim of this study was to further characterize this disorder and determine the optimal management strategy.

METHODS
We describe a case of a 76-year-old female with iatrogenic immunodeficiency associated PCNSL successfully treated with surgical resection followed by an antiviral and rituximab based regimen. We then performed a systematic literature review and identified 58 cases of non-transplant iatrogenic immunodeficiency associated LPD involving the CNS. We used a linear probability statistical model to determine correlations with outcome.

RESULTS
Natalizumab was associated with EBV negative tumors (p = 0.023), and EBV positive tumors were associated with improved outcomes (p = 0.016). Surgical resection was associated with improved outcomes (p = 0.032), although limited by potential confounding effect. Antiviral treatment (p = 0.095), rituximab (p = 0.111), and SCT (p = 0.198) showed a trend toward improved outcomes. The remaining treatments including methotrexate showed no improvement.

CONCLUSION
We propose that surgical resection, rituximab, and antiviral treatment may be considered as an alternative to standard HD-MTX based regimens when managing iatrogenic immunodeficiency associated LPD of the CNS. Further study through prospective cohort studies or randomized clinical trials is warranted.
EPID-20. MORTALITY TRENDS IN PRIMARY MALIGNANT BRAIN AND CENTRAL NERVOUS SYSTEM TUMORS VARY BY HISTOPATHOLOGY, AGE, RACE, AND SEX
Authors: Thierheimer Marisa , Cioffi Gino , Waite Kristin , Kruchko Carol , Ostrom Quinn , Barnholtz-Sloan Jill 
Published: November 2022

Abstract

BACKGROUND
Primary malignant brain and other central nervous system tumors (BT) are rare cancers that have shown rising mortality rates in recent years. To elucidate potential factors involved in this rising death rate, we examined mortality trends for primary malignant BT in the United States (US) stratified by histopathology groupings, age, race, and sex.

METHODS
Mortality rates for demographic factors within primary malignant BT were generated using the Center for Disease Control’s National Vital Statistics Systems (NVSS) data from 2004 to 2018. Additionally, histopathology-specific incidence-based mortality rates were calculated using the National Cancer Institute’s Surveillance, Epidemiology, and End-Results (SEER) 18 data from 2004 to 2018. Joinpoint modeling was used to estimate mortality trends and annual percent changes (APC) with corresponding 95% confidence intervals (CI).

RESULTS
Overall, there was a very small increase in mortality from 2004-2018 (NVSS, APC: 0.3%, 95% CI: 0.1%-0.5%). Individuals 65+ years of age saw a small increase in mortality (NVSS, APC: 0.6%, 95% CI: 0.4%-0.9%), while changes in individuals of other ages were non-significant. Asian/Pacific Islander or American Indian/Alaskan Native had the largest increase in mortality (NVSS, APC: 1.6%, 95% CI: 0.7%-2.4%). Overall mortality trends by sex were similar. Among histopathology groupings, there was a small mortality increase in adults ages 65+ years with glioblastoma (SEER, APC: 0.5%, 95% CI: 0.1%-1.0%), while patients with other glioma and non-glioma did not show significant changes in mortality. In pediatric patients (ages 0-14 years), high-grade glioma mortality increased significantly from 2004-2015 (SEER, APC: 7.0%, 95% CI: 3.8%-10.3%) but had a non-significant decrease from 2015-2018. Pediatric patients with embryonal tumors had a significant mortality decrease between 2004 and 2018 (SEER, APC: -1.9%, 95% CI: -3.3%-0.5%).

CONCLUSION
Examining age, race, sex, and histopathology-specific mortality at the population level can provide important information for clinicians, researchers, and aid in public health planning.
EPCO-04. TRANSCRIPTIONAL AND CHROMATIN-ACCESSIBILITY HETEROGENEITY IN IDH-MUTANT GLIOMAS
Authors: Lyne Anne-Marie , Ducray François , Cavalli Florence 
Published: November 2022

Abstract
Diffuse gliomas are a common type of adult brain tumour, comprising about 80% of adult malignant brain tumours, and are incurable. IDH-mutant gliomas, oligodendroglioma and astrocytoma, can be treated initially but eventually recur and are generally fatal. In this study, we profiled and analysed 23 frozen samples from primary and recurrent IDH-mutant glioma patients with single nucleus multiome sequencing (RNA- and ATAC-seq). In total we assayed around 70,000 malignant cells as well as 30,000 cells from the tumour microenvironment. Using a matrix factorisation approach, we characterised biological signals in the malignant cells from each sample, thereby identifying known and novel processes which vary within and recur across samples. Trajectory analysis was used to reconstruct the developmental hierarchy in IDH-mutant glioma and to investigate plasticity at different hierarchy levels, highlighting differences and similarities across patients and cancer types. Finally, master regulators, which drive malignant transcriptional programs were identified, using the complimentary and concurrent RNA and chromatin accessibility assays. This study provides a unique opportunity to investigate the transcriptomic and epigenetic heterogeneity present in gliomas, as well as the events leading to the development of more aggressive and treatment-resistant glioma tumours.