bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPID-01. PROFILE AND OUTCOME OF PATIENTS WITH BRAIN METASTASES IN YOGYAKARTA, INDONESIA
Authors: Malueka Rusdy , Hartanto Rachmat , Setyawan Nurhuda , Rismawan Alfian , Dananjoyo Kusumo , Basuki Endro , Asmedi Ahmad , Dwianingsih Ery 
Published: November 2022

Abstract

BACKGROUND
Metastatic brain tumors cause significant morbidity and mortality and often have a poor prognosis. Currently, there are limited epidemiology data on metastatic brain tumors in Indonesia. This study aimed to identify demographic, clinical characteristics, and outcomes of patients with brain metastases in Yogyakarta Province, Indonesia.

METHODS
Demographic and clinicopathological data were collected from medical records of brain tumor patients admitted to six major hospitals in Yogyakarta Province, Indonesia, for five years (2015–2019).

RESULTS
In total, 395 patients were included. Most patients were females (254, 64.3%). The mean age of the patients was 51.6±15.0 years old. Headache was the most common presenting symptom (53.2%), followed by a motoric deficit (48.4%), cognitive impairment (24.3%), loss of consciousness (21.3%), and a seizure (20.8%). The most common primary tumors that metastasize to the brain were lung (36.6%) and breast cancer (32.7%). The median overall survival of patients with brain metastases was 11±2.36 months.

CONCLUSION
Lung and breast cancers are the most common source of brain metastases in Yogyakarta, Indonesia. Overall survival of patients with brain metastases in this area is still relatively short.
EPID-06. IMPROVEMENTS IN SURVIVAL FOR GLIOBLASTOMA IN THE POST-STUPP PROTOCOL ERA
Authors: Neff Corey , Chavez Gordon , Proescholdt Christina , Kruchko Carol , Cioffi Gino , Waite Kristin , Barnholtz-Sloan Jill , Ostrom Quinn 
Published: November 2022

Abstract

BACKGROUND
Introduction of the Stupp protocol for glioblastoma treatment in 2005 led to a significant increase in overall survival in glioblastoma. Prior analyses identified additional survival gains in glioblastoma since this time, though the source of these gains is unknown. In this analysis, we leveraged commercial claims and population-based datasets to better understand potential treatment factors associated with improved survival for glioblastoma.

METHODS
Provider-side commercial claims data were obtained from IQVIA for adults (18+) diagnosed with malignant brain tumor (ICD-9 codes: 191.0-191.9 or ICD-10 codes: C71.0-C71.9) from 2013-2021. Glioblastoma patients were identified as those who received biopsy/resection, radiation and temozolomide within 60 days of their brain tumor diagnosis. Treatment patterns were determined using ICD-9/ICD-10 procedure codes and HCPCS/CPT codes. Date of death was determined by a claim containing the CPT codes 99238 or 99239 or date of last claim followed by at least 30 days of no additional claims. Population-based survival data for microscopically-confirmed adult glioblastoma cases receiving radiation treatment from the National Program of Cancer Registries (NPCR) from 2004-2018 were used as a comparison group. Median survival was estimated using Kaplan-Meier regression, overall in IQVIA and by two-year periods in NPCR.

RESULTS
In the IQVIA cohort, 9,368 individuals (2.5%) were identified as glioblastoma based on treatment criteria. Median survival in the IQVIA cohort 16.6 months (15.2-17.0), and 12 months (95%CI:12-12) in NPCR. Median survival in NPCR increased from 11 months in 2004-2006, to 12 months in 2006-2009, and then 13 months in 2010-2018. Within the IQVIA cohort, 27% had ≥ 1 claim for Bevacizumab and 15% had ≥ 1 claim for tumor treating fields.

CONCLUSIONS
Survival in glioblastoma continues to improve over time, which may be due to developments of new therapeutic approaches. Assessment of population-level survival patterns is essential for understanding the impact of treatment advancements in the general population.
EPID-07. A SYSTEMIC REVIEW OF PHASE II SINGLE-ARM TWO-STAGE DESIGNS IN GLIOBLASTOMA
Authors: Yoo Wonsuk , Mehta Shwetal , Sanai Nader 
Published: November 2022

Abstract
Even though two-stage designs have been popularly in oncology Phase 2 single-arm trials during last decade, none, to our knowledge, has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in glioblastoma. It might be valuable to perform a comprehensive review on the phase 2 single-arm two-stage trials in glioblastoma for examination of appropriate application on the two-stage designs. Systematic review has been performed under the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. The search was performed using following key words for the literature search as index terms or free-text words: “phase II trials”, “glioblastoma”, and “two-stage design”. After identifying 81 articles based on online search, we had 32 studies included in review due to exclusion of 49 articles such as duplicates (n = 10), randomized trials (n = 7), single-stage designs (n = 5), and insufficient information (n = 27). We extracted general and two-stage design information (tumor type and setting, drugs, error types, response rates, primary endpoint, two-stage sample size data, study termination status etc). Almost 50% of single-arm two-stage studies failed to provide key information related to study designs and sample size calculation, even wrong power analysis and interpretation. Response rate and progression-free survival are used as popular surrogate endpoints for overall survival. It is time to evaluate other potential endpoints like post-progress survival and hazard ratio, and usefulness of co-primary endpoint. Studies less than 10% provided the historical data source. Investigators should keep transparency of the trials by fully providing and citing historical data source and do conservative choice for historical rates. Meta-analysis can be a good option to accurately estimate the historical control. The appropriate selection on primary endpoint, historical control data, incorporation of adaptive designs, right application of two-stage designs might help overcoming the challenges on glioblastoma therapeutic trials.
EPID-13. CHARACTERIZATION OF PEDIATRIC RADIATION-INDUCED MENINGIOMA: A SEER ANALYSIS
Authors: Matharoo Jashanjeet , Abaricia Jefferson , Opalak Charles , Broaddus William 
Published: November 2022

Abstract

OBJECTIVE
Radiation-induced meningiomas (RIM) are the most common secondary neoplasm arising from radiation therapy. RIM have not been characterized in pediatric populations on a national scale despite displaying shorter latency and higher malignancy rates in institutional studies. The objective of this study was to characterize pediatric RIM and compare latency and malignancy rates to those of adult RIM using the National Cancer Institute’s Surveillance, Epidemiology and End Results Program (SEER) database.

METHODS
From the SEER Research Plus Nov 2020 (1975-2018) dataset, 56161 patients treated with EBRT for ocular/orbital tumors, brain/nervous system tumors, and leukemia were identified. 185 patients meeting criteria for RIM were selected: cranial/spinal EBRT (presumed from diagnostic indication), histologically distinct precedent tumor treated with EBRT, and a minimum 5-year latency from EBRT to meningioma diagnosis. This sub-population was divided into 2 groups – pediatric (ages 0-19, n = 10) and adult (ages &gt; 20, n = 175) RIM – and latency, recurrence rate and multiplicity were compared for each group. The number of tumors classified as malignant (as opposed to benign or borderline malignant) was also compared between groups. Additionally, demographic data were compared for each group.

RESULTS
Of the pediatric RIM patients, 70% were male, 70% were Caucasian, and 10% were African American. No pediatric RIM patients experienced a recurrence or presented with multiple RIMs. The pediatric group showed lower latency (11.00 ± 1.94 years, p &lt; 0.001) and a higher malignancy rate (30%, p = 0.002) than the adult group (latency of 23.38 ± 8.69 years; malignancy rate 5.1%).

CONCLUSION
These data represent the first characterization of pediatric RIM from a national database and support prior findings of shorter latency and higher malignancy rates in pediatric vs adult RIM, as well as lay the groundwork for future nationwide monitoring of this rare yet highly significant complication.
EPID-15. SURGICAL RESECTION OF BENIGN MENINGIOMAS IN THE ELDERLY POPULATION: IMPLICATIONS FROM A PROPENSITY-SCORE MATCHED ANALYSIS
Authors: Ma Jun , Zhu Ping , Chen Clark 
Published: November 2022

Abstract

Object
We characterized the patterns of clinical practice in benign meningioma resection and survival outcome as a function of patient age using the Surveillance, Epidemiology and End Results (SEER) and the SEER-Medicare database.

METHODS
The likelihood for recommendation to proceed with resection and survival in adult, benign meningioma patients were characterized using logistic regression. Survival analysis was performed using a propensity-score matching (PSM)-method (covariates balanced in PSM: socio-demographics, facility features, and comorbidities) through a multivariable logistic regression and accelerated failure time (AFT) models.

RESULTS
The likelihoods of recommendation for surgery were 0.59 (95%CI = 0.53-0.66, P &lt; 0.001) and 0.17 (95%CI = 0.15-0.21, P &lt; 0.001) for meningioma patients age 60-79 and ≥ 80, relative to patients age 40-59. Expectedly, the hazard of death increased with advancing aging strata in patients who underwent meningioma resection. To account for mortality risk associated with normal aging, a PSM analysis was performed to calculate the hazard of death for surgically resected meningioma patients relative to an age- and PSM-matched cancer-free patient cohort. This odds ratio (OR) was 3.84 (95%CI: 3.15-4.67, P &lt; 0.001) for patients age 60-79 and 3.41 (95%CI: 2.56-4.56, P &lt; 0.001) for patients age ≥ 80. These two ORs were not statistically different (ROR: 0.89, 95%CI: 0.63-1.62, P = 0.512), suggesting that the likelihood of death after benign meningioma resection was not significantly elevated in patients age ≥ 80 after accounting for expected age-related mortality.

CONCLUSION
Our study suggests that surgeons exert caution in selecting elderly with meningioma for resection. After accounting for mortality risk associated with normal aging and patient selection by the surgeon, the likelihood of death for patients age ≥ 80 who underwent meningioma resection was comparable to that observed for patients age 60-79.
EPID-16. SEASONAL INCIDENCE PATTERN COMPARISON BETWEEN PRIMARY AND SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMAS
Authors: Yang Rachel , Demopoulos Alexis , Li Jianyi 
Published: November 2022

Abstract

OBJECTIVE
To compare primary CNS lymphoma [PCNSL] and secondary CNS lymphoma [SCNSL] incidence by year, month, week, and time between symptom onset, radiographic study, and tissue diagnosis.

BACKGROUND
PCNSL is a rare non-Hodgkin’s B-cell lymphoma confined to the central nervous system with an increased incidence among immunocompromised patients and immunocompetent patients.1 Epstein Barr Virus [EBV] infection usually accompanies immunocompromised patients with PCNSL. Whether viral infection is etiologic remains uncertain, especially among the immunocompetent, where EBV is not found. A seasonal pattern was described suggesting an infectious etiology.2 We sought to add to the literature our experience regarding patterns of disease onset. Design/

METHODS
We retrospectively identified 96 immunocompetent PCNSL patients and 75 SCNSL patients treated here between 2010-20. Complete data was available for 91 PCNSL and 73 SCNSL patients. Variables collected included symptom onset, initial imaging, and tissue collection dates.

RESULTS
Weekly incidence was noted in both, with peak of incidence in the 10th and 40th week in PCNSL in 9th, 27th, and 31st weeks among SCNSL. Time between symptom onset and first neuroimaging study was significantly different, with PCNSL patients having significantly less time on average. Curiously, the average time between each PCNSL diagnosis was significantly shorter than that for SCNSL diagnosis.

CONCLUSION/RELEVANCE
Due to the rarity of the disease, larger studies are needed to further elucidate potential viral etiologies underlying PCNSL.
EPID-19. CHANGES IN SURVIVAL OVER TIME FOR ALL PRIMARY BRAIN AND OTHER CNS TUMORS IN THE UNITED STATES
Authors: Edelson Jacob , Waite Kristin , Cioffi Gino , Kruchko Carol , Ostrom Quinn , Barnholtz-Sloan Jill 
Published: November 2022

Abstract

BACKGROUND
Despite advances in cancer diagnosis and clinical care, survival for many primary brain and other central nervous system (CNS) tumors remain poor. This study performs a comprehensive survival analysis on these tumors.

METHODS
Survival differences were determined utilizing the National Program of Cancer Registries Survival Analytic file for all primary brain and other CNS tumors. Overall survival and survival of the 5 most common histopathologies within specific age groups (children ages 0-14 years, adolescents, and young adults [AYA] ages 15-39 years, and older adults ages 40+ years) were determined. Overall survival was compared for three time periods: 2004-2007, 2008-2012, and 2013-2017. Kaplan-Meier and multivariable Cox proportional hazards models were used to generate median survival, hazard ratios (HR) and 95% confidence intervals (CI). Models were adjusted for sex, race/ethnicity, and treatment pattern. Malignant and non-malignant brain tumors were assessed separately.

RESULTS
Aside from hemangioma and mesenchymal tumors in older adults, no notable changes in survival were observed across the time periods for non-malignant tumors. For malignant brain tumors, significant survival improvements were observed in children with embryonal tumors (logrank p = 0.00028) and in AYA with anaplastic astrocytoma (logrank p = 0.0043). In older adults, significant improvement was observed in the five most common histopathologies except oligodendroglioma. Adjusted for sex, race/ethnicity, and treatment, there were improvements in survival in 2008-2012 and 2013-2017, when compared to 2004-2007, in children and AYA with malignant tumors (Children: HR = 0.92, 95% CI = 0.87-0.98, p = 0.010 in 2008-2012; HR = 0.91, 95% CI = 0.85-0.97, p = 0.005 in 2013-2017; AYA: HR = 0.92, 95% CI = 0.88-0.96, p &lt; 0.001, in 2008-2012; HR = 0.87, 95% CI = 0.83-0.93, p &lt; 0.001 in 2013-2017).

CONCLUSIONS
Overall survival for malignant brain and other CNS tumors improved slightly in 2013-2017 for all age groups as compared to 2004-2007. No significant changes were observed for non-malignant brain and other CNS tumors.
EPID-21. INCORPORATING RECEIPT OF STANDARD-OF-CARE AS A KEY VARIABLE IN POPULATION-BASED STUDY OF GLIOBLASTOMA SURVIVAL
Authors: Zhu Ping , Chen Clark 
Published: November 2022

Abstract

Object
Populational database research with real-world settings offers epidemiologic insight at scales that cannot be easily recapitulated, especially for rare cancers such as glioblastoma. However, most survival studies were conducted without consideration for whether the patients received the standard of care (SOC).

METHODS
Survival analysis was performed using the National Cancer Database (NCDB) and stratified for Methyl-guanine-methyl transferase (MGMT) promotor methylation. Glioblastoma patients age &lt; 40 were excluded to minimize the prognostic impact of isocitrate dehydrogenase (IDH) mutations. SOC was defined as the receipt of chemotherapy and radiation within 2-6 weeks of surgical biopsy or resection. Sensitivity analyses were performed allowing chemotherapy and radiation start date to differ by 0, 3, 5, and 10 days.

RESULTS
Within the NCDB (N = 11231), 54.7% of newly diagnosed glioblastoma patients did not receive SOC. The median survival time (MST) estimates were significantly shorter for all glioblastoma patients (10.9, IQR: 4.3-21.5, months) relative to SOC treated patients (15.3, IQR: 8.6-26.2, months; p &lt; 0.001). The MST estimates remain stable in sensitivity analysis allowing for 0, 3, 5, and 10-day discrepancy between chemotherapy and radiation start date. These results were recapitulated using the SEER-Medicare database. The MST estimates for MGMT methylated and unmethylated glioblastoma patients after SOC in the NCDB were 21.0 and 14.5-mo, respectively. The overall and MGMT-specific survival estimates mirror those reported by the SOC arms of five recent randomized controlled studies. Analysis of all glioblastoma patients indicates survival benefit of immunotherapy (HR: 0.90, p = 0.020) while such benefit was absent in SOC treated patients (HR: 0.97, p = 0.644) - with the latter observation more reflective with trial results and clinical experiences.

CONCLUSION
Survival analysis in the populational database study can be misleading without information on the receipt of SOC.
EPID-25. THE CLINICAL AND MOLECULAR LANDSCAPE OF GLIOMAS IN ADOLESCENTS AND YOUNG ADULTS
Authors: Bennett Julie , Nobre Liana , Sheth Javal , Ryall Scott , Fang Karen , Johnson Monique , Negm Logine , Chung Jiil , Komosa Martin , Nunes Nuno , Lim-Fat Mary Jane , Perry James , Sahgal Arjun , Detsky Jay , Bouffet Eric , Hazrati Lili-Naz , Dirks Peter , Ertl-Wagner Birgit , Kongkham Paul , Zadeh Gelareh , Mason Warren , Cusimano Michael , Das Sunit , Gao Andrew , Tsang Derek , Nguyen Lananh , Laperriere Normand , Keith Julia , Munoz David , Tabori Uri , Hawkins Cynthia 
Published: November 2022

Abstract

OBJECTIVE
Gliomas in adolescents and young adults (AYA) are commonly treated with a standard chemo-radiation approach. Molecular alterations have not been comprehensively described to date.

METHODS
We compiled a multi-institutional cohort of patients diagnosed with glioma between 15-39.9 years over 20 years. Molecular analysis, therapeutic data and outcome was collected. For specific alterations, analysis included patients aged 0-39.9 years.

RESULTS
A total of 1900 patients with 876 AYA gliomas were included. Ongoing analysis reveals genetic alterations in 95% of available tumours. IDH p.R132H was found in 49% of tumours, while non-canonical IDH mutations were found in 7%. Paediatric-type mutations were found in 33% of AYA tumours with IDH-WT GBM accounting for the remaining 11%. The most common paediatric alterations in AYAs included BRAF p.V600E (11%) and FGFR alterations (7%) while BRAF fusions, H3 p.K27M and H3.3 p.G34R were rarely observed (4%, 4% and 1% respectively). BRAF fused tumours with non-canonical binding partners were enriched in AYAs. Analysis of BRAF-V600E gliomas between ages 0-40 revealed increased tendency for malignant tumours in patients &gt; 20 years suggesting malignant transformation possibly due to higher rate of secondary hits. This resulted in worse overall-survival for AYA patients with BRAF-V600E glioma when compared to children under 20 years (p=0.0032). Ten-year OS of 100%, 90% and 95% was seen for BRAF fused, BRAF-V600E and FGFR-altered AYA low grade glioma respectively, compared to 14% and 25% for BRAF-V600E and FGFR-altered high grade glioma. In contrast, continuous decline was observed in the IDH-mutant gliomas with 10-year OS of 50% which declined to 29% at 15 years.

CONCLUSIONS
Gliomas in AYA often have non-canonical alterations that may evade standard molecular analysis. They are enriched for paediatric-type alterations with distinct molecularly-based outcomes. These tumours may respond to targeted inhibitors and would benefit from comprehensive diagnostic and therapeutic approaches.
EPCO-01. EPIGENETIC REPROGRAMMING SHAPES THE MOLECULAR AND CELLULAR LANDSCAPE OF SCHWANNOMA
Authors: John Liu S , Casey-Clyde Tim , Swinderman Jason , Cho Nam Woo , Vasudevan Harish , Foster Kyla , Pekmezci Melike , Chen William , Villanueva-Meyer Javier , Hiam-Galvez Kamir J , Swaney Danielle , Choudhury Abrar , Breshears Jonathan , Stevenson Erica , Chen Kuei-Ho , Lien Brian , Wu David , Lang Ursula , Magill Stephen , Lim Daniel , McDermott Michael , Berger Mitchel S , Perry Arie , Krogan Nevan J , Spitzer Matthew , Gilbert Luke , Theodospoulos Philip , Raleigh David 
Published: November 2022

Abstract
DNA methylation profiling provides robust classification of nervous system tumors, but mechanisms driving epigenetic identity of individual tumor types are incompletely understood. Integrating DNA methylation profiling (n=76), RNA sequencing (n=24), single-cell RNA-sequencing (n=9), and mass cytometry (n=9), we discovered vestibular schwannomas are comprised of two epigenetic groups distinguished by neural crest development pathways or repair and regeneration pathways driving immune infiltration. Analyses of preoperative magnetic resonance imaging studies (n=66) or paired primary and recurrent schwannomas (n=13) suggested radiotherapy was sufficient but not necessary for epigenetic reprogramming of neural crest enriched schwannomas into immune enriched schwannomas. In support of this hypothesis, DNA methylation profiling, RNA sequencing, single-cell RNA sequencing, proteomic mass spectrometry, and lymphocyte migration assays demonstrated radiotherapy epigenetically reprogramed viable schwannoma cells to secrete immunomodulatory signals and recruit lymphocytes in vitro. Genome-wide CRISPRi screens identified histone acetyltransferases or DNA methyltransferases driving schwannoma radiotherapy responses, including the epigenetic regulators KDM5C or KDM1A. CRISPRi and lymphocyte migration assays ± radiotherapy confirmed KDM5C drives schwannoma immune infiltration whereas KDM1A inhibits schwannoma immune infiltration. To define genomic mechanisms underlying epigenetic group identity, we performed pooled CRISPRi screening coupled with single-cell RNA sequencing (Perturb-seq) of 44 schwannoma markers. In parallel, we developed single nuclei profiling of chromatin accessibility through paired ATAC sequencing and RNA sequencing coupled with pooled CRISPRi screening (snARC-seq) of 54 epigenetic regulators identified by our genome-wide CRISPRi screen. Functional genomic approaches revealed the tyrosine phosphatase PTPRG as a regulator of survival, and KDM5C and KDM1A as regulators of inflammation. In summary, we report two epigenetic groups of schwannomas and mechanisms underlying epigenetic group identity using a new functional genomic technique allowing for simultaneous interrogation of single-cell epigenetic and gene expression changes in the context of genetic and therapeutic perturbations. These data elucidate a novel epigenetic mechanism of action of radiotherapy.