bluuebunny/crossref_metadata_2025_split huggingface dataset:
DDDR-32. EXPLORING ANDROGENIC MODULATION IN GLIOBLASTOMA: POTENCY AND SELECTIVITY OF NOVEL NORETHINDRONE DERIVATIVES
Authors: Dudley Richard , Schneider Ryan , Shoemaker Carson , Stitzlein Lea 
Published: November 2024

Abstract

BACKGROUND
Glioblastoma (GBM) represents the most frequently diagnosed malignant CNS tumor in adults and remains incurable. Despite the identification of several oncogenic drivers contributing to tumor formation, targeted therapy with brain-penetrant inhibitors has afforded little progress in survival outcomes. Interestingly, gender has been shown to increase the incidence of GBM, with men having roughly a 50-60% increase in incidence compared to women in the US. This statistic led to research on the involvement of and subsequent inhibition of androgen synthesis and signaling in cell culture models and tumor samples.

METHODS
To further investigate the potential involvement of steroidal hormones in GBM proliferation, our lab synthesized a series of norethindrone (NE) derivatives with varied molecular weights, steric bulk, and lipophilicity to modulate the androgenic activity of NE. The small library was tested in several GBM cell lines, including U87, A172, and T98G cells, using cell viability assays.

RESULTS
One derivative, a lipophilically modified version of NE synthesized via a one-pot click reaction, was shown to have improved potency compared with parental NE (&gt;5-fold). The lipophilic NE derivative had IC50 value of 22 uM, 15 uM, and 35 uM in the U87, A172, and T98G cells, respectively. This molecule was tested in immortalized normal human astrocyte (NHA) cells and found to have an IC50 value of 34 uM suggesting some selectivity.

DISCUSSION
Given this derivative’s activity in GBM models and modest selectivity, we plan to screen it in additional GBM cell lines (LN-18 and U251) and eventually in glioma stem cell models. Future research will focus on identifying key targets involved in the mechanism of action, including the impact of lipophilic addition to the steroid nucleus and its effect on androgenic activity and downstream signaling. We will investigate these effects using RPPA and co-treatments with androgen receptor antagonists and 5-alpha reductase inhibitors.
EPID-09. THE NATURAL HISTORY AND MOLECULAR ARCHITECTURE OF INCIDENTAL MENINGIOMAS
Authors: Nguyen Minh , Chen William , Mirchia Kanish , Magill Stephen , Morshed Ramin , Raleigh David 
Published: November 2024

Abstract
The prevalence of asymptomatic, incidental meningiomas is increasing due to greater frequency of brain imaging. This retrospective cohort study of adult patients presenting at a single institution from 1996-2020 integrated clinical data, serial magnetic resonance imaging (MRI) volumetrics, DNA methylation profiling, and targeted gene expression profiling to define the natural history and molecular architecture of incidental meningiomas. Volumetrics were calculated from contrast-enhanced brain MRIs at time of diagnosis compared to serial surveillance MRIs (average 3 MRIs per patient pre-intervention, range: 1-12) DNA methylation groups and gene expression risk scores were defined for 123 samples that underwent resection. Time-to-event analyses were performed for progression-free survival (PFS), symptom-free survival (SFS), and treatment-free survival (TFS). The cohort included 238 meningiomas from 207 patients. Median age at diagnosis was 59 years and 81.5% of patients were female. Median clinical and imaging follow-up were 9.1 and 6.7 years, respectively, during which time 50.8% progressed. Median maximum diameter and volume at diagnosis were 2.20 cm and 4.25 cm3, respectively, and median pre-treatment volumetric growth rate was 19.2% per year. Median pre-treatment PFS and TFS were 3.10 and 1.27 years, respectively, and median SFS and post-treatment PFS were not reached. Cox proportional hazards regression identified maximum diameter at diagnosis as a significant predictor of worse pre-treatment PFS (multivariate HR 1.65 per 1 cm [95% CI 1.19–2.28], p=0.0027) and worse TFS (multivariate HR 1.44 per 1 cm [95% CI 1.17–1.76], p&lt;0.001). Skull base tumors had with worse SFS (multivariate HR 2.48 [95% CI 1.02–6.00], p=0.045). Molecular and histological features among incidental meningiomas that ultimately underwent resection (n=176, 74.0%) were reassuring (89.2% WHO grade 1, 10.2% WHO grade 2). These findings suggest maximum diameter at diagnosis of incidental meningiomas is significantly associated with earlier progression and eventual treatment, and skull base tumors have earlier symptom development.
EPID-14. PATTERNS OF CARE AND PROGNOSTIC FACTORS FOR PATIENTS WITH BRAIN METASTASES FROM COLON CANCER: A REAL-WORLD STUDY
Authors: Jayram Diya , Hodgson Lydia , Bellur Shreyas , Ahmad Shahzaib , Sommer Samuel , Ozair Ahmad , Frias Numa , Ahluwalia Manmeet 
Published: November 2024

Abstract

BACKGROUND
Brain metastases (BMs) from colon cancer (CC) have limited published literature. This work sought to examine patterns of care and prognostic factors for patients with CC BMs.

METHODS
A retrospective study was conducted on patients with CC BMs in the National Cancer Database between 2010-2020 and reported using STROBE guidelines. Treatment was stratified into receipt of stereotactic radiosurgery only (SRS), whole brain radiation only (WBRT), systemic therapy only (Sys), combination therapy, and no brain-directed treatment (NoTx). Median overall survival (mOS) and prognostic factors were determined using multivariate cox proportional hazards adjusting for age, sex, race/ethnicity, insurance, Charlson-Deyo score (CDS), concurrent metastases (CMs), and treatment. Outcomes were reported as hazard ratio (HR) and 95% confidence intervals.

RESULTS
Among 1,383 BMs patients, median age was 64.0 years (IQR 56.0-73.0). 46.4% were female and 81.2% were White. Overall mOS (95% CI) was 5.6 months (4.5-6.2). 26.1% had bone, 71.5% had lung and 72.4% had liver CMs. 24.4% underwent WBRT+Sys, 22.6% NoTx, 18.5% Sys, 14.8% SRS+Sys, 14.7% WBRT, and 5.0% SRS. Patients who underwent SRS+Sys had the highest mOS of 14.4 months (12.8-16.3) followed by Sys: 11.6 months (8.6-13.4), WBRT+Sys: 9.5 months (8.5-10.9), SRS: 3.2 months (2.5-4.4), WBRT: 2.5 months (2.2-2.8), and NoTx: 2.5 months (2.2-2.8) (P&lt;0.001). Patients treated with WBRT+Sys (HR:1.2, 1.0-1.5, P=0.028), SRS alone (HR:1.8, 1.4-2.5, P&lt;0.001), WBRT alone (HR:3.6, 2.9-4.4, P&lt;0.001), NoTx (HR:2.5, 2.0-3.0, P&lt;0.001) was associated with significantly lower survival than SRS+Sys. Patients treated at non-academic facilities (HR:1.1, 1.0-1.3, P=0.038), with Medicare-insurance (HR:1.2, 1.1-1.5, P=0.013) and with left-sided mCC (HR:0.8, 0.7-0.9, P&lt;0.001) had lower survival.

CONCLUSIONS
SRS+Sys was associated with the highest survival in patients with CC BMs, however only 14.8% received it. Notably, 22.6% of patients received NoTx. Further prospective studies exploring factors behind heterogeneity in clinical care are warranted.
EPID-16. GENOMIC ANCESTRY-RELATED RISK RATIOS FOR GLIOBLASTOMA INCIDENCE AMONG GLOBAL POPULATIONS AND RACIAL/ETHNIC GROUPS WITHIN THE UNITED STATES
Authors: Ballard Christine , Giang Minh Huy , Ostrom Quinn , Walsh Kyle 
Published: November 2024

Abstract
Glioblastoma (GBM) incidence varies globally, elevated rates in Europe and lower rates in Asia, Latin America, and Africa. While partially attributable to national differences in cancer diagnosis and reporting practices, analogous patterns exist within diverse Western nations. Ancestry-associated differences in GBM risk allele frequencies (RAFs) could contribute, a hypothesis supported by our prior multiethnic genome-wide association studies (GWAS). Leveraging variant effect estimates from large GBM GWAS datasets and ancestry-stratified allele frequency data from diverse reference populations (ALFA, GNOMAD, 1000 Genomes Project), we estimate the extent of GBM incidence differences across populations that can be attributed to underlying variation in RAF at the seventeen known GBM risk loci. Aggregate differences in RAF between global populations (Europe, West-Africa, East Asia) were associated with a &gt;20% reduction in the normalized GBM risk-ratio (RR) in Africans compared to Europeans (RR=0.78) and a &gt;50% reduction in East Asians compared to Europeans (RR=0.47). The frequency of GBM risk alleles was generally highest in Europeans, but four alleles found most commonly in Africans are at loci regulating telomere maintenance (TERC, TERT, OBFC1/STN1, RTEL1). We repeated analyses using RAF data from U.S. populations (African-Americans, Latinos, and non-Hispanic Whites). Compared to non-Hispanic Whites, aggregate differences in RAF were associated with a 15% reduction in GBM risk among African-Americans (RR=0.85) and a 28% reduction among Latinos (RR=0.72). We conclude that a sizable proportion of the reduced GBM incidence in Latinos and Asians, relative to non-Hispanic Whites, can be accounted for by population-level differences in RAF at known loci. However, registry-based analyses consistently report a two-fold lower incidence of GBM in African Americans relative to non-Hispanic Whites which is poorly explained by RAF differences at known loci. Further work is needed to identify structural, environmental, and biological factors contributing to unresolved differences in GBM incidence.
EPID-17. REAL-WORLD OUTCOMES OF BRAIN METASTASES FROM PANCREATIC CANCER: AN ANALYSIS OF 1266 PATIENTS
Authors: Jayram Diya , Bellur Shreyas , Ahmad Shahzaib , Ozair Ahmad , Steger Julia , Sommer Samuel , Frias Numa , Ahluwalia Manmeet 
Published: November 2024

Abstract

BACKGROUND
Brain metastases (BMs) from pancreatic cancer (PC) are uncommon. This study examined patterns of care and clinical outcomes for PC BMs.

METHODS
A retrospective analysis was conducted on PC BMs patients in the US National Cancer Database between 2010-2020, following STROBE guidelines. Treatments were categorized into systemic therapy (Sys) alone, stereotactic radiosurgery (SRS)±Sys, whole brain radiation (WBRT)±Sys, and no brain-specific treatment (NoTx). Primary outcome was median overall survival (mOS), with corresponding hazard ratio for death (HR) and 95% confidence intervals. Prognostic factors were determined using multivariable Cox proportional-hazards analysis including age, sex, race/ethnicity, insurance, Charlson-Deyo score (CDS), concurrent metastases (CMs), and treatment type.

RESULTS
Of 170,071 metastatic PC patients, 1,266 (0.7%) PC BM patients were included. 45.7% were female and 81.3% were White. Median age was 66.0 years (IQR:58.0-74.0). 34.4% had bone CMs, 45.4% had lung CMs, 60.2% had liver CMs. 48.1% of patients received NoTx, 22.6% Sys, 12.4% WBRT+Sys, 9.8% WBRT, 4.6% SRS+Sys, and 2.5% SRS. mOS (95% CI) was 2.4 months (2.2-2.5) in patients with BMs and 3.9 months (3.8-3.9) in those without BMs (P&lt;0.001). Amongst BM patients, SRS+Sys had a significantly higher mOS of 7.8 months (6.1-14.3) followed by WBRT+Sys: 5.2 months (4.2-6.8), Sys: 4.8 months (4.2-5.8), WBRT: 2.0 months (1.6-2.2), SRS: 1.8 months (1.4-3.7), and NoTx: 1.2 months (1.0-1.3) (P&lt;0.001). Patients treated with SRS alone (HR:2.9, 1.8-4.7, P&lt;0.001), WBRT alone (HR:2.9, 2.0-4.0, P&lt;0.001), and Sys alone (HR:1.5, 1.1-2.1, P=0.009) had significantly lower survival than with SRS+Sys. Patients treated in nonacademic facilities (HR:1.3, 1.1-1.4, P&lt;0.001) and those with CMs (HR:1.4, 1.2-1.6, P&lt;0.001) had poorer survival.

CONCLUSIONS
BMs in PC are rare and associated with lower survival. SRS+Sys was associated with the best prognosis, but &lt;5% received it. 48% of patients receiving NoTx had mOS of 1.2 months. Future studies exploring care variations are warranted.
EPID-30. THE COST OF HOSPITAL-BASED CARE AMONG CANADIAN PATIENTS WITH MALIGNANT CENTRAL NERVOUS SYSTEM TUMOURS IN COMPARISON TO THOSE WITH LUNG AND COLORECTAL CANCERS IN THE YEAR PRECEDING THEIR CANCER DIAGNOSIS
Authors: Xu Linwan , Zhou Keyun , Yuan Yan , Walker Emily 
Published: November 2024

Abstract

BACKGROUND
Approximately 12% of the Canadian GDP was spent on healthcare in 2023. While hospital-based care (HC) constitutes a significant portion of this expenditure, the costs may vary depending on the cancer type. We investigate the HC cost of patients with malignant central nervous system tumours (CNS cancer) and compare it to patients with common cancers in Canadian provinces.

METHODS
We obtained data between 2010 and 2014 from the Canadian Institute for Health Information’s in-patient and ambulatory care datasets. HC cost was estimated using a 12-month look back period prior to diagnosis date for each patient, including cost related to cancer diagnosis and general healthcare. Choosing colorectal (CRC) and lung (LC) cancers to be the common cancers, patients who were 15 years of age or older and had a diagnosis of one of these cancers were included. We used quantile regression to investigate the factors associated with HC cost.

RESULTS
A total of 4,498 (CNS), 41,028 (CRC) and 29,747 (LC) patients were included from Alberta and Ontario, Canada. Encounter type (in-patient/out-patient), province (AB/ON), and comorbidities (Yes/No) were the top three factors contributing to HC cost. Adjusting for encounter type, comorbidities and age, the HC costs for CNS patients were $0.7k and $2.4k higher than CRC patients at 50th and 90th percentile, respectively, and $1.0k higher than LC patients at 90th percentile in Ontario. While in Alberta, HC costs for CNS patients were $0.2k and $0.8k higher than CRC patients at 50th and 90th percentile, respectively, and $1.0k lower than LC patients at both 50th and 90th percentiles.

CONCLUSIONS
We compared HC cost among Canadian patients with different cancer types; significant HC cost differences between patients with CNS and common cancer were observed. Further investigations are warranted to understand drivers of the cost differences.
EPID-31. IMPACT OF THE COVID-19 PANDEMIC ON THE UTILIZATION OF STEREOTACTIC RADIOSURGERY AMONG RACIAL MINORITIES DIAGNOSED WITH BRAIN METASTASES
Authors: Zhu Ping , Chen Clark ,   N3C Consortium
Published: November 2024

Abstract

OBJECTIVES
Brain metastases (BM) is the most common form of adult brain tumors and one of the devastating consequences of cancer. Stereotactic radiosurgery (SRS) is an established and effective treatment for oligometastatic BMs. We examined how COVID-19 pandemic impacted clinical utilization of SRS in BM treatment and generalize such impact to outpatient care for patients with all cancer types.

METHODS
Three national-scale datasets were used: National Cancer Database (NCDB,N=5,238), the National COVID Cohort Collaborative database (N3C, N=13,106 for BM, N=203,706 for all cancer types), and SEER. Multivariable logistic regression models were performed to determine whether the pandemic affected clinical utilization of SRS in BM treatment and chemotherapy initiation for all cancer types.

RESULTS
Prior to 2019 (pre-pandemic), we observed no racial disparity in the odds of receiving SRS between non-Hispanic white (NHWs) and non-Hispanic black (NHBs) BMs in both NCDB and N3C. Between 2020 and 2021 (pandemic), however, NHBs were significantly less likely to receive SRS comparing to NHWs in both NCDB (NHB:aOR-0.77,p=0.002) and N3C (NHB:aOR-0.78,p&lt;0.001). In SEER, the age-adjusted incidence rate of BM remained unchanged when comparing pre- and post-pandemic periods. Further substantiating the impact of COVID-pandemic on racial disparity in outpatient care for all cancer patients, we showed that NHB patients were more likely to receive delayed chemotherapy (&gt;60 days since diagnosis of cancer) compared to NHWs during the pandemic (aOR-1.10, p&lt;0.001), but such association was not detected before pandemic. Ratio of odds ratio (ROR) analysis confirmed that NHB patients comparing to NHWs during pandemic experienced 1.11-fold difference in the odds of delayed chemotherapy between NHBs and NHWs before pandemic [ROR=1.11, p&lt;0.001].

CONCLUSION
Racial disparity in SRS-receipt for BM patients has been exacerbated during COVID-19 pandemic and such impact could be generalized to outpatient care for all cancer types. Understanding the determinants giving rise to this disparity should augment the readiness of our cancer care infrastructure in anticipation of future pandemics or other public health crises.
EPID-32. ELEVATED SERUM IGE IS LINKED TO IMPROVED GLIOBLASTOMA SURVIVAL, PARTICULARLY AMONG FEMALES
Authors: Francis Stephen , Guerra Geno , Nakase Taishi , Kachuri Linda , McCoy Lucie , Hansen Helen , Wiemels Joseph , Wiencke John , Molinaro Annette , Wrensch Margaret 
Published: November 2024

Abstract
Prior epidemiological research shows a correlation between serum immunoglobulin E (IgE) levels and decreased risk of glioma. However, the relationship between IgE and the prognosis of glioma remains poorly understood. This study seeks to investigate how factors such as sex, tumor subtype, and IgE class influence the association of serum IgE levels with both glioma risk and survival outcomes. METHODS- In this investigation, we conducted a case-control study utilizing participants enrolled in the UCSF Adult Glioma Study from 1997 to 2010. We measured serum IgE levels for total, respiratory, and food allergy in adults diagnosed with glioma (n=1,696), and controls (n=1,135) matched based on age, sex, and race/ethnicity. Logistic regression, adjusted for patient demographics, was employed to evaluate the correlation between IgE levels and glioma risk. Multivariable Cox regression, adjusted for patient-specific and tumor-specific factors, was utilized to compare survival outcomes between the elevated and normal IgE groups. RESULTS- Increased levels of total IgE were linked to a decreased risk of both IDH wildtype (OR=0.65, 95% CI: 0.54-0.78) and IDH mutant glioma (OR=0.65, 95% CI: 0.50-0.85). In multivariable Cox regression analysis, heightened respiratory IgE levels were associated with enhanced survival among individuals with IDH wildtype glioma (HR=0.78, 95% CI: 0.67-0.91). Notably, this improved survival was more pronounced in females (HR=0.71, 95% CI: 0.53-0.96) compared to males (HR=0.80, 95% CI: 0.66-0.97), resulting in median survival improvements of 6.2 months (P&lt;.001) and 1.6 months (P=0.003), respectively. CONCLUSION- Increased levels of serum IgE were associated with reduced risk of glioma overall, and improved prognosis for IDH wildtype glioma, which was particularly strong in females. These findings hint at potential sexual dimorphism in the antitumor activity of IgE-mediated immune responses, suggest an important role for IgE assessment in glioblastoma clinical trial design, and provide justification for investigations into IgE-based therapeutics.
EPID-35. COLLISION TUMORS AT THE SKULL BASE: UNVEILING A PETROCLIVAL MENINGIOMA COEXISTING WITH A GROWTH HORMONE-PRODUCING PITUITARY ADENOMA
Authors: Choi Yoon , Hsu Frank , Dai-Ju Jenny , Kuan Edward , Patel Vivek 
Published: November 2024

Abstract
Collision tumors are rare occurrences characterized by coexistence of two histologically different tumor types within the same anatomical location. While collision tumors involving skull base meningiomas and pituitary adenomas are uncommon, they pose distinct diagnostic challenges. We report the case of a 57-year-old female initially diagnosed with petroclival meningioma WHO 1, subsequently found to harbor a collision tumor with a growth hormone-producing pituitary adenoma. The patient initially presented with aphasia, right-sided weakness, and gait instability, prompting a diagnosed of left petroclival mass with left temporal horn entrapment. Patient underwent craniotomy and partial resection of the tumor in 2022 and was diagnosed with meningothelial meningioma, WHO1. The patient had history of uncontrolled diabetes and physical features of large hands with hypertrophied terminal phalangeal tufts but patient reported that she has had similar hands since childbirths for decades. Screening pituitary function tests were ordered due to the petroclival meningioma involving suprasellar region, revealing significantly elevated growth hormone, and insulin-like growth factor-1(IGF-1) levels, raising suspicion for pituitary adenoma. Subsequent endoscopic resection of the sellar mass via a transsphenoidal approach in 2024 confirmed the presence of somatotroph pituitary neuroendocrine tumor. Retrospectively growth hormone producing pituitary adenoma likely contributed to patient’s uncontrolled diabetes and coarse, large hands. This case highlights the importance of a high index of suspicion for collision tumors, particularly in patients with skull base tumors involving supra sellar region, especially when presenting with atypical clinical features.
DISP-05. SUPERVISED MACHINE LEARNING PREDICTION OF THERAPEUTIC CLINICAL TRIAL ENROLLMENT FOR MINORITY PATIENTS AND WOMEN IN NEURO-ONCOLOGY
Authors: Mehari Mulki , Warrier Gayathri , Dada Abraham , Kabir Aymen , Haskell-Mendoza Aden , Reihl Sheantel , Jackson Joshua , Gonzalez Ariel , Reason Ellery , Flusche Ann , Dalton Tara , Negussie Mikias , gonzales Cesar Nava , Chukwueke Ugonma , Molinaro Annette , Porter Alyx , Fecci Peter , Hervey-Jumper Shawn 
Published: November 2024

Abstract

BACKGROUND
Despite changes in national policy, women and minority patients remain under-accrued in glioma clinical trials. Supervised machine learning may serve as a novel approach to understanding which variables and their complex interplay most influence enrollment for underrepresented patients. We aimed to design and externally validate machine learning models to predict therapeutic clinical trial enrollment for a) all patients, b) women, and c) NIH-designated minority patients with low- and high-grade glioma.

METHODS
In a 20-year retrospective cohort of 1042 adult patients with low- and high-grade glioma, boosted neural network (BNN) models for the whole, women, and minority cohorts were used to analyze the combined effects of demographic, socioeconomic, and oncologic variables on clinical trial enrollment. These models were validated using an external cohort (n=103).

RESULTS
In the development cohort (445 [42.7%] women; 151 [14.5%] minorities; median age, 51.5 [interquartile range: 39.4-62.5] years), 350 patients (33.6%) enrolled in a therapeutic clinical trial. The whole cohort BNN (AUC: 0.827, misclassification rate (MR): 0.175), the women cohort BNN (AUC: 0.895, MR: 0.125), and the minority cohort BNN (AUC: 0.983, MR: 0.053) models accurately predicted trial enrollment on external validation. For the whole cohort and women models, several demographic (race, ethnicity, minority status, sex), socioeconomic (insurance, employment status), and oncologic variables (seizure, chemotherapy, KPS, WHO grade, tumor lobe) were equally influential (Main effect (ME): 1.000, Total effect (TE): 1.000) on enrollment. For the minority model, socioeconomic variables including insurance status (ME: 0.089, TE: 0.417) and occupation classification (ME: 0.087, TE: 0.381) drove enrollment.

CONCLUSION
We designed and externally validated the first machine learning model for predicting therapeutic clinical trial enrollment for patients with diffuse glioma. Model features driving trial enrollment varied for underrepresented patients. These results may help prioritize personalized patient-specific initiatives to address barriers to equitable patient accrual.