bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPID-04. EVOLVING SURVIVAL IN PATIENTS WITH LEPTOMENINGEAL METASTASES FROM SOLID TUMORS
Authors: Chabot Kiana , Osei-Gyening Isaiah , Estrera Rachel , Yang Jonathan , Pentsova Elena , Boire Adrienne , Wilcox Jessica 
Published: November 2023

Abstract

BACKGROUND
The prognosis for patients with leptomeningeal metastases (LM) has been historically bleak, with an average survival &lt; 4 months and limited treatment options. As modern therapeutics prolong the lives of cancer patients, the life expectancy of those with LM may also improve. This study aims to demonstrate survival trends in patients with LM over a 20-year time span.

METHODS
This is a single-institution retrospective analysis of patients diagnosed with solid tumor LM, excluding primary brain tumors, between 2002-2022. LM diagnosis was determined via unequivocal radiographic enhancement, CSF cytology, and CSF circulating tumor cell enumeration (CSF-CTC, cells/3mL). Patient characteristics, CSF-CTC enumeration at diagnosis, and therapeutic interventions post-LM were collected. Median overall survival (OS) with IQRs were calculated.

RESULTS
A total of 626 patients with LM were identified. The median age at LM diagnosis was 59 years (range, 13-86) with a female predominance (72.5%). Primary malignancy consisted of lung (45.2%), breast (35.7%), melanoma (4.0%), and other (15.1%). The 20-year median OS in patients with lung cancer was 4.8 months (1.9-13.0), breast cancer was 6.1 months (2.0-13.7), and melanoma was 7.1 months (2.8-14.5). Median OS was prolonged in patients with a CSF-CTC count ≤ 50 versus &gt; 50 (8.9 vs 3.4 months, p&lt; 0.0001). Patients who received LM-directed proton craniospinal irradiation (17.1%), photon involved-field radiation (45.5%), and no radiation (37.4%) had a median OS of 8.7 months (4.3-20.2), 4.3 months (1.5-9.1), and 3.4 months (1.2-12.5), respectively. Patients diagnosed with LM between 2017-2022 trended towards superior median OS (6.2 months, 2.2-14.0) compared to those diagnosed between 2002-2016 (5.3 months, 2.2-12.2).

CONCLUSION
In this largest known series of patients with LM, outcomes show signs of improvement. Superior survival trends emerge based on primary malignancy, early detection, and modern treatment modalities. Further analyses will define survival trends by patient characteristics, cancer subtypes, and systemic therapies.
EPID-05. PATTERNS OF RECOMMENDATION FOR SURGICAL INTERVENTION IN GRADE II, III, AND IV ASTROCYTOMAS: IMPLICATIONS FOR DELAYED DIAGNOSIS AND TREATMENT
Authors: Yekula Anudeep , Zhu Ping , Chen Clark 
Published: November 2023

Abstract

INTRODUCTION
Timely surgical acquisition of tumor tissue for definitive diagnosis forms the foundation for early cancer diagnosis and treatment. Here we examined the pattern of surgical recommendations in the treatment of intracranial astrocytoma.

METHODS
Grade 2, 3, and 4 astrocytoma (abbreviated as A2, A3, and A4) patients who underwent biopsy for histologic diagnosis were identified in NCDB (2010-2021) and SEER (2004-2019) and divided into those who received recommendation for biopsy on initial presentation and those who received recommendation against surgery but ultimately underwent biopsy. Demographic, clinical characteristics, and survival outcomes of these cohorts were compared.

RESULTS
In both the NCDB and the SEER, patients ultimately diagnosed with A2 (NCDB: aOR=1.88, p&lt; 0.001; SEER: aOR=1.77, p&lt; 0.001) and A3 (NCDB: aOR=1.97, p&lt; 0.001; SEER: aOR=1.78, p&lt; 0.001) were less likely to receive recommendation for biopsy during initial encounter relative to patients with glioblastoma after adjusting the covariates. Other factors associated with decreased likelihood of recommendation for biopsy included: advanced age, deep cortical/infratentorial location, and smaller tumor size. These findings remain robust after accounting for dehydrogenase (IDH) mutation status, which was available in the NCDB after 2018. In a multivariable model accounting for survival-pertinent variables, including medical comorbidities, A2 (NCDB: aHR=1.23, p=0.006; SEER: aHR=1.15, p=0.039) and A3 (NCDB: aHR=1.44, p&lt; 0.001; SEER: aHR=1.53, p&lt; 0.001) patients who received recommendation against biopsy during initial encounter exhibited worse survival.

CONCLUSION
Patients with A2 and A3 are more likely to receive recommendation against surgical intervention on initial encounter. The associated survival pattern bears relevance to the potential impact of delayed diagnosis and treatment.
EPID-07. DISTANT PROGRESSION TO THE POSTERIOR FOSSA IN SUPRATENTORIAL GLIOBLASTOMA: A REPORT OF THREE CASES DURING TUMOR TREATING FIELDS THERAPY
Authors: Kiyokawa Juri , Tamura Kaoru , Shimizu Kazuhide , Ota Tetsuo , Imae Shogo , Sakashita Mai , Yamamoto Shinji , Maehara Taketoshi 
Published: November 2023

Abstract

BACKGROUND
Distant progression of supratentorial glioblastoma (GBM) to the posterior fossa is rare. We report three cases in which such distant progression was observed during Tumor Treating Fields (TTFields) therapy. CASES: All three cases involved solitary supratentorial tumors. Biopsy was performed in case 1 (61-year-old male) and partial resection in cases 2 (69-year-old female) and 3 (73-year-old male). The diagnosis was IDH-wildtype GBM in all three cases. TTFields therapy was performed following chemoradiotherapy. In case 1, distant progression was observed in the dorsal side of the medulla oblongata at 7 postoperative months and in the left cerebellum at 23 postoperative months. The patient died 5 months later. In case 2, distant progression was evident in the pons at 41 postoperative months and the patient died 3 months later. In case 3, distant progression was observed in the cerebellum at 5 postoperative months and the patient died 3 months later. Autopsy was performed in case 1 and revealed multiple separate GBM lesions in the supra- and infratentorial space. Although there was histological heterogeneity within lesions, there was no clear histological difference between supra- and infratentorial lesions.

DISCUSSION
In the EF-14 trial, although there were no cases of GBM progression to the posterior fossa in the control group who did not receive TTFields therapy (0/122 cases), such progression occurred in 3.6% (11/306) of cases in the TTFields-treated group (p&lt; 0.001). Even though TTFields therapy affords good local control of GBM, distant progression might occur in the posterior fossa, where the electric field effect is poor. Further accumulation and analysis of such cases is warranted.
EPID-11. THE IMPACT OF THE COVID-19 PANDEMIC ON TREATMENT PATTERNS IN GLIOBLASTOMA
Authors: Neff Corey , Price Mackenzie , Cioffi Gino , Waite Kristin , Kruchko Carol , Bryan Iorgulescu J , Barnholtz-Sloan Jill , Ostrom Quinn 
Published: November 2023

Abstract

BACKGROUND
The COVID-19 pandemic and subsequent shutdowns led to significant disruptions in medical care and access to treatment for all medical conditions in the US in 2020. Institutional cohorts and survey-based studies have shown that there was significant care disruption for individuals diagnosed with primary brain tumors. In this analysis, we utilized a database containing ~80% of brain tumor diagnoses to assess the national impact of the pandemic on treatment patterns for glioblastoma.

METHODS
Data on newly diagnosed glioblastoma were obtained from the National Cancer Database, which includes hospital registry data from Commission on Cancer accredited facilities, for diagnosis years 2018-2020. Logistic regression was used to generate odds ratios (OR) of receiving resection, chemotherapy, or radiation after diagnosis in 2020 as compared to 2018-2019, after adjustment for potential confounders, including age at diagnosis, sex, race and ethnicity, insurance status, income, patient distance from diagnosing facility, Charlson comorbidity score, facility type and location, and MGMT methylation.

RESULTS
There were 7,184 glioblastoma, of which 5,873 were IDH-wt, diagnosed in 2020, a 3% decrease from the 2018-2019 average. For individuals with any newly diagnosed glioblastoma, there was a decrease in odds of resection (OR=0.91, p=0.047). Among those with any glioblastoma and a subset with IDH-wt glioblastoma there was a reduction in odds of radiation (OR=0.87, p=0.004 and 0.85, p&lt; 0.001, respectively) and chemotherapy (OR=0.87, p=0.002 and 0.89, p=0.026, respectively). No decrease in odds of treatment was associated with a prior positive SARS-CoV-2 PCR test.

CONCLUSIONS
The COVID-19 pandemic caused significant disruption to health care for cancer patients in the US in 2020. For individuals with glioblastoma, in-person treatments decreased in frequency for individuals diagnosed in 2020 as compared to prior years. Further research is required to determine the impact this treatment disruption had on outcomes.
EPID-12. SURVIVAL IS ASSOCIATED WITH CIRCULATING B-CELLS AND AGE AMONG OLIGODENDROGLIOMA PATIENTS
Authors: Taylor Jennie , Warrier Gayathri , Hansen Helen , McCoy Lucie , Rice Terri , Guerra Geno , Francis Stephen , Clarke Jennifer , Bracci Paige , Kelsey Karl , Wrensch Margaret , Molinaro Annette , Wiencke John 
Published: November 2023

Abstract

BACKGROUND
Though patients with oligodendroglioma have improved outcomes versus astrocytomas, there remains marked variability in their survival experience that is unexplained by known prognostic factors. Immunomethylomics uses DNA methylation as a substitute for flow cytometry to characterize immune cells in whole blood.

METHODS
We applied immunomethylomics to archived blood samples from patients enrolled in the UCSF Adult Glioma Study including oligodendrogliomas (141); other adult diffuse glioma subtypes (347); and controls (454).

RESULTS
Median age of oligodendrogliomas was 44 years (range 19 – 83), 57% male, 75% white, and 60% received chemotherapy prior to blood draw. Oligodendroglioma patients had lower percent of B cell fractions (total, memory, naïve) than people without glioma. They also had higher percent of B cell (total, memory) and lymphocyte fractions (total, CD4-total and memory), basophil, eosinophil, and NK cells versus other glioma subtypes. Median overall survival in oligodendrogliomas was 17.5 years (95% CI 16.9 - NA) with median follow-up of 12 years (95% CI 11 – 14). Recursive partitioning analysis delineated two survival groups for oligodendroglioma patients based on age and percent B naïve cells. Best outcome, with median survival of 24.2 years (95% CI 20.4 – NR), was seen in patients &lt; /= 42 years of age with a higher percent of B naïve cells ( &gt;1.91%) (N = 37). Worst outcome, with median survival of 16.9 years (14.8 – NR), was seen in patients &lt; /= 42 years of age with a lower percent of B naïve cells (&lt; /= 1.91%) (N = 28) OR patients &gt; 42 years of age (N = 76) (p = 0.00032).

CONCLUSIONS
An interaction between age and B naïve cell percentages may predict survival for oligodendroglioma patients. Immunomethylomics is a powerful tool for assessing immune status and these findings suggest that blood-immune profiles may be prognostic glioma patients.
EPID-14. ASSOCIATION OF ELEMENTAL IRON WITH GLIOBLASTOMA PATIENT OUTCOMES
Authors: Shenoy Ganesh , Kuhn Madison , Sahu Aurosman , Khristov Vladimir , Heebner Madison , Wilding Hannah , Clegg Taylor , Bhanja Debarati , Wade Quinn , Liermann Laura , Wang Dongxiang , Smith Nataliya , Khunsriraksakul Chachrit , Palsa Kondaiah , Slage-Webb Becky , Zacharia Brad , Proctor Elizabeth , Connor James R 
Published: November 2023

Abstract
Very few studies have examined the role of trace metals, such as iron, in glioblastoma biology and patient outcomes. Here we directly measured iron content in matched glioblastoma tumor and plasma samples using inductively coupled plasma mass spectroscopy (ICP-MS) or inductively coupled plasma atomic emission spectroscopy (ICP-AES), and then studied associations of iron with clinical parameters such as median overall survival (mOS). Elemental iron analysis was performed on a total of 31 glioblastoma samples, 21 of which had matched plasma samples that were analyzed together. Plasma samples from age-matched healthy volunteers were used as a control for comparisons against plasma from glioblastoma patients. Plasma samples from glioblastoma patients had higher levels of iron compared to age-matched healthy control samples (1307.2 ng/mL vs. 575.2 ng/mL, P = .000013). Among glioblastoma patients, higher levels of plasma iron were associated with prolonged survival (mOS: 20.7 months vs. 12.4 months, P = 0.0063). Plasma iron levels, however, were not significantly correlated with tumoral iron levels (R = 0.095, P = 0.70), indicative of regulation between plasma and brain iron. Unsurprisingly, high tumor iron content failed to significantly associate with survival. To gain insights into whether iron may be associated with immune function, we analyzed plasma samples with multiplexed immunoassays. Glioblastoma plasma samples that contained higher levels of iron were associated with increased IFN-β (10.91 pg/mL vs 7.43 pg/mL, P = 0.004) and PDGF-AB/BB (1275.3 pg/mL vs 492.8 pg/mL, P = 0.009), whereas no such association was observed in healthy plasma samples. Our results demonstrate that plasma iron is associated with clinical outcomes and potentially with alterations in IFN-β and/or PDGF-AB/BB signaling in glioblastoma patients. These findings illustrate the importance of iron in glioblastoma biology and demonstrate its potential prognostic value.
EPID-16. A MULTI-CENTER, PROGRESSION-FREE SURVIVAL ANALYSIS IN IDH-MUTANT GLIOMAS WITH CDKN2A DELETION: IMPLICATIONS FOR PROGNOSIS AND CLINICAL TRIAL DESIGN
Authors: Miller Julie , Hsieh Annie , Nohman Amin , Reuss David , Eyuepoglu Ilker , Cahil Daniel , Jungk Christine , Juratli Tareq 
Published: November 2023

Abstract
Homozygous deletion of CDKN2A is an important predictor of poor prognosis in patients with IDH-mutant gliomas. The updated 2021 WHO classification now recognizes this alteration as sufficient for the designation of an astrocytoma, IDH-mutant, WHO Grade 4, which otherwise requires histological observation of necrosis or microvascular proliferation. While overall survival patterns associated with CDKN2A deletion have been well-described, we sought to characterize progression-free survival (PFS) in this patient population. Across three institutions (Massachusetts General Hospital, Boston; University Hospital Heidelberg, Heidelberg; TU Dresden, Dresden), we identified 48 patients with IDH-mutant gliomas in which CDKN2A deletion was detected at the time of diagnosis, followed for a median of 15.2 years. The average age of the cohort is 35 years, with 60% of the patients identified as male. Most patient received immediate treatment after surgery, with 81% of the cohort undergoing radiation therapy and 73% receiving chemotherapy. Based on RANO criteria, the median progression-free survival of this patient population is 2.8 years (95% CI 1.4 – 3.3 years) and median overall survival is 4.3 years (95% CI 2.1 – 6.6 years). A positive T2/FLAIR mismatch sign or lack of contrast enhancement on MRI at the time of diagnosis are both associated with improved PFS in univariate regression analysis. For comparison, we identified a control cohort of 51 patients with astrocytoma, IDH-mutant, grade 4 without CDKN2A deletion from MGH, achieving grade 4 by histologic criteria. Demographics were similar to the CDKN2A-deleted cohort, with median age (37 years) and percentage of male patients (60%). Notably, however, PFS for the grade 4, CDKN2A-intact, IDH-mutant glioma comparison group is estimated at 5.9 years (95% CI 3.3 – 7.9 years). Overall, these data reinforce the accelerated disease course associated with deletion of CDKN2A in IDH-mutant gliomas, providing an important reference for clinical trial design.
EPID-17. ANTIBODY REACTIVITY TO VARICELLA ZOSTER VIRUS IS ASSOCIATED WITH IMPROVED GLIOMA SURVIVAL AND IS MODIFIED BY GERMLINE HLA POLYMORPHISMS
Authors: Francis Stephen , Guerra Geno , Hansen Helen , Wiencke John , Wrensch Margaret 
Published: November 2023

Abstract
Antigenic reactivity towards varicella zoster virus (VZV) has shown a consistent reduction in glioma risk across multiple studies on multiple continents. To our knowledge this is the virus to be robustly associated with reduced risk of any cancer. Our recent work has shown that high VZV reactivity is also assumed with improved glioma prognosis. Using the UKBioBank we have previously shown that germline HLA polymorphism, rs9273325, significantly effects reactivity to VZV. In this study we investigate the VZV glioma survival association in the context of germline HLA polymorphisms. METHODS: We measured quantitative IgG reactivity towards VZV gE, and conducted genome wide array based genotyping in 891 adults with glioma. Associations of patient IgG levels (1st quartile vs. quartiles 2,3,4) with overall survival were estimated using Cox models adjusted for age, sex, self-reported race, surgery type, dexamethasone usage at blood draw. RESULTS: VZV seroreactivity was significantly associated with reduced mortality (HR=0.83, 95% CI: 0.70-0.99; p=0.034), as expected from our previous study. Among patients with rs9273325-GG, higher levels of VZV antibodies were associated better prognosis (HR=0.75, 0.62-0.92; p=0.005), but in the rs9273325-GA/AA strata this relationship with VZV antibodies was not observed (HR=0.94, 0.66-1.35; p=0.75). Similar results were observed in grade IV gliomas, IDHwt GBMs. CONCLUSIONS: Strong antibody response to VZV is associated with improved glioma prognosis and the effect of VZV reactivity on glioma survival is modified by a specific HLA polymorphism, a Gene x Virus interaction, that is unlikely due to chance. This study highlights the importance of accounting for HLA variation in immune related studies, including oncolytic viral therapies. Our findings also point towards a potentially MHC mediated mechanism by which VZV could be priming an immune response targeting glioma cells. Further investigations into this mechanism and VZV/shingles vaccination as a potential glioma therapeutic are warranted.
EPID-20. SEX-SPECIFIC DIFFERENCES IN MENINGIOMA SUBTYPES AND MUTATIONS – A RETROSPECTIVE ANALYSIS
Authors: Berghaus Natalie , Hielscher Thomas , Suwala Abigail , Ippen Franziska Maria , Ratliff Miriam , Herold-Mende Christel , Wick Wolfgang , von Deimling Andreas , Sahm Felix 
Published: November 2023

Abstract
A variety of intrinsic and extrinsic factors are known to influence and promote the development of cancer. Although the patients’ gender can influence extrinsic factors, biological sex is an important intrinsic factor. Here, it must also be considered that hormone levels change over the lives of patients. To further investigate these aspects, meningioma can serve as a prototype tumor. Differences are already obvious when analyzing the epidemiology and outcomes: Females are more frequently diagnosed with meningioma, but high-grade meningiomas and fatal outcomes are more frequently observed in males. To further resolve sex and potentially hormone-specific differences, we retrospectively examined a dataset of 798 patients (females n=541, males n=257). Additionally, we arbitrarily set a cut-off of 58 years to stratify for females between pre- and post-menopause. The male cohort was analyzed accordingly to exclude an age-dependent effect. Further, the female cohort was subdivided into “45-55 years” and “other” to analyze the impact of high hormone fluctuations within menopause. When examining the histological data, we found that women displayed the chordoid subtype more frequently than men (6.3% vs. 1.6%). In the age-dependent analyses, there may be a signal for a hormone-dependent effect, as for females this subtype was diagnosed more frequently &lt; 58 than &gt; 58 years of age (10.6% vs. 1.9%; males: 0% vs. 3.0%) and within the menopause (15.5% vs. 3.2%). The same pattern was noted for the TRAF7 mutation, which was detected more frequently in females (20.2% vs. 7.7%), females &lt; 58 years (23.9% vs. 15.6%, males: 6.2% vs. 9.1%) and females within the menopause (27.9% vs. 17.6%) than in the respective other subgroups. This preliminary data warrants further research in larger, comprehensively annotated cohorts and analysis for hormone levels and receptor expression.
EPID-21. EPIDEMIOLOGY AND CLINICOPATHOLOGICAL FEATURES OF MENINGIOMA PATIENTS: FINDINGS FROM NATIONAL BRAIN CENTER HOSPITAL INDONESIA
Authors: The Yuli Felistia , Amanda Nadira Fildza , Susanto Nugroho Harry , Salam Sardiana , Prayanti Diorita , Maharani Viola , Baziad Chairunnisa , Lumempouw Silvia Francina , Miftahussurur Muhammad 
Published: November 2023

Abstract

BACKGROUNDS
Meningioma is considered as one of high prevalence disease, eight cases per 100.000 population, among intracranial tumours. This study aimed to assess the epidemiology and clinicopathological features of meningioma patients.

METHODS
This is a retrospective cohort study of hospitalized meningioma patients, excluding spinal meningioma, in National Brain Hospital, Jakarta, Indonesia between 2020 and 2022. Patient’s characteristics, symptoms, MRI results before surgery, and MRI results after surgery were obtained from medical records. Chi-square test, Fisher’s exact test, and logistic regression analysis performed with p-value &lt; 0.05 was considered as significant.

RESULTS
We analysed 325 patients between 2020 and 2022, which number increases per year. Meningioma grade I was predominant than grade II and III, however grade II and III patients were slightly older than grade I patients (mean age 47.6 ± SD 13.7 years and 46.9 ± 10.3 years, respectively). The majority of patients were females than males with 4 to 1 ratio. The most common locations of brain meningioma were convexity (26.8%), followed by parasellar (11.7%), and falx (34%). Preoperative clinical symptoms in the form of muscle weakness (p=0.04), vision problem (p=0.02), hearing impairment (p=0.006), slusrred speech (p=0.003), and ptosis (0.01) were significantly related to more severe meningioma grading. However, in multivariable logistic regression only hearing impairment was significantly related with meningioma grading with odds ratio 0.313 (95% CI 0.113-0.869, p=0.02).

CONCLUSIONS
Meningioma prevalence alarming rise should get more attention. Especially as this tumor usually occurs productive age population. Clinical symptoms are associated with the severity, however further study is needed to support our finding.