bluuebunny/crossref_metadata_2025_split huggingface dataset:
Difference in presentation of pediatric and adult ependymoma: An NCDB analysis.
Authors: Tuman Jaylin , Anderson Quinton , Hsia Beau , Wu Xinxin , Silberstein Peter T. 
Published: June 2023

e14055 Background: Ependymomas originate from ependymal cells and account for 6.2% of primary brain tumors in the pediatric population. Adult and pediatric ependymomas are identical in histology, but present in different sites, with intracranial ependymomas seen in children and spinal ependymomas more frequent in adults. The unique presentation of ependymoma in children warrants exploration separate from adults; however, there is currently limited data providing a baseline understanding of pediatric ependymoma and those that it impacts. The National Cancer Database (NCDB) was analyzed to identify common presentations and demographic characteristics of ependymoma in children. Methods: Patients aged 18 and younger with a diagnosis of Ependymoma (ICD 9391-9394) were identified utilizing the National Cancer Database (NCDB) from 2004 – 2020 for a retrospective cohort analysis (N = 2,098). Demographic factors such as age, sex, race, ethnicity, primary site, insurance status, and surgical procedure were analyzed by descriptive statistics. Additionally, identical NCDB data was identified for patients over 18 years old for use as a comparison factor (N = 8,227). Results: A total of 2,098 pediatric patients were identified with an average age of diagnosis of 7.0 years (SD = 5.609, range = ( < 1) - 18 years) with a higher percentage being male (55.9%) than female (44.1%). The vast majority of cases of pediatric ependymoma originate in the brain (91.2%), followed by occurrences on the spinal cord and cranial nerves (8.8%). This differs from ependymoma in adults where only 44.8% of cases occur in the brain and 55.2% occur in the spinal cord. Of the 2,098 pediatric patients identified, they were histologically identified as either Ependymoma, NOS (51.5%), or Anaplastic Ependymoma (47.5%). Comparatively, Anaplastic Ependymoma makes up only 9.7% of ependymomas in adult populations. Additionally, the majority of patients were Non-Hispanic (76.3%) and white (76.9%). Most patients were privately insured (58.0%) followed by those insured by Medicaid (33.1%). Pediatric ependymoma is primarily treated with surgical resection (95.7%). Conclusions: Compared to adult occurrences, pediatric cases of ependymoma are not only unique in the site that they affect but also in histology, with a higher proportion of anaplastic ependymoma. This NCDB analysis is the first to specifically analyze pediatric ependymoma and fills a gap in our understanding of how this cancer presents in children. The majority of ependymoma patients are non-Hispanic and White with a primary site occurring in the brain rather than in the spinal cord, consistent with literature. These findings emphasize the importance of a deeper understanding of the nature of this disorder. Future research should further explore the impact of demographic and socioeconomic factors on the treatments utilized, and overall survival of pediatric patients with ependymoma.
A preclinical study to evaluate the combination of azeliragon, an inhibitor of the receptor for advanced glycation endproducts (RAGE), with radiation therapy as a potential treatment of glioblastoma.
Authors: Ghosh Subhajit , Huang Jiayi , Hallahan Dennis , Marcus Stephen Garrett , Thotala Dinesh 
Published: June 2023

e14056 Background: Systemic lymphopenia, which is independently associated with poor overall survival, is observed in approximately 30-50% of patients with glioblastoma (GBM) after chemoradiotherapy. We recently found that cranial irradiation of GBM tumors increases circulating myeloid-derived suppressor cells (MDSC) contributing to systemic lymphopenia. Additionally, we found that cranial radiation increases circulating levels of the RAGE ligands S100A8/9 and HMGB1, which have been reported to increase MDSC and their immunosuppressive effects through binding RAGE. We, therefore, hypothesized that targeting RAGE receptors on MDSC could prevent immunosuppression and improve survival in preclinical GBM models. Methods: We orthotopically implanted GBM cells (GL261 and CT2A) into immunocompetent C57BL6 mice. The GBM tumor-bearing mice were treated with five doses of fractionated radiation therapy (RT, 2 Gy/day for 5 consecutive days) to the whole head in combination with RAGE inhibitor azeliragon (0.1mg/mice/day i.p starting one day before RT for up to 10 days). We evaluated the immune cells in the tumor microenvironment (TME) and spleen at 14 days post-tumor implantation. We also evaluated the circulating immune cells and RAGE ligands (HMGB1 and S100A8/A9) in the plasma at 7, 14, and 21 days post-tumor implantation and monitored the mice for survival up to 60 days. Results: GBM tumor-bearing mice (GL261 & CT2A) treated with RT plus azeliragon had significantly improved survival when compared to RT alone or azeliragon alone. RT plus azeliragon significantly reduced the accumulation of granulocytic-MDSC (G-MDSC), monocytic-MDSC (M-MDSC), tumor-associated macrophages (TAM), and regulatory T cells (Treg), while increasing infiltrating CD8 T cells in the TME as compared to RT alone. RT alone significantly increased the accumulation of G-MDSC and M-MDSC in the spleen, which was significantly reduced with concurrent azeliragon. Concurrent administration of azeliragon with RT did not significantly affect the radiation-induced increase of circulating M-MDSC as well as plasma HMGB1 and S100A8/A9 concentration, though there was a modest reduction of circulating G-MDSC. Conclusions: Our study indicates that azeliragon, by blocking RAGE interaction with its ligands, helps to overcome the MDSC-mediated immunosuppression that occurs after RT. The combination of azeliragon with RT enhances survival in preclinical models. Clinical trials evaluating the safety and efficacy of azeliragon in combination with RT for newly diagnosed GBM are currently under development.
Hints for reclassification of meningiomas based on the fifth edition of WHO CNS.
Authors: Cheng Chuandong , Han Tiantian , Guo Didi , Kong Rongrong , Chen Siqi , Dong Yuwei , Wang Mengjuan , Ding Ran , Deng Wanglong , Bu Fanfeng , Wang Yuan 
Published: June 2023

e14059 Background: Meningioma is the most common primary neoplasm of the central nervous system (CNS) in adults. Genetic variants ( NF2, AKT1, TRAF7 etc.) are strongly related to the subtypes of meningioma. TERT promoter mutation or homozygous CDKN2A and/or CDKN2B deletion are independent evidence for diagnosing WHO grade 3 meningioma according to 5th CNS WHO. Our study reclassifies meningiomas using a clinical and molecular real-world dataset. Methods: This study retrospectively analyzed the genomic alteration of 347 Chinese meningioma patients during 2019-2022. Next-generation sequencing (NGS) was performed to detect gene mutations in tumor samples. Results: TERT promoter mutation or CDKN2A/B deletion were identified in 11% (n = 39) of patients ( TERT 5.2%, CDKN2A 8.1%, CDKN2B 8.6%). Of these cases, histologic grade information was available for 26 patients, 14(53.8%) of whom were reclassified as WHO grade 3 meningiomas, including four histologic grade 1 and ten histologic grade 2. There is a male preponderance in reclassified patients (56.4% vs. 40.0%, p < 0.05), meanwhile the age showed no significant difference between them (average age: 54 vs 50, p = 0.11). The most frequently co-mutated gene was NF2. The proportion of TERT promoter mutation or CDKN2A/B deletion in NF2-mutant tumors was similar to NF2-wildtype tumors (10% vs. 11%, p > 0.05). Conclusions: In our study, 11% of Chinese adult meningioma patients found TERT promoter mutation or CDKN2A/B deletion and showed a male preponderance, among 53.8% of whom were reclassified as meningiomas WHO grade 3. Overall, these data advance the understanding of the significance of molecular profiling in the classification of meningioma patients according to the 5th WHO CNS.
Outcomes of stereotactic radiosurgery in central nervous system lymphoma: A single institution experience.
Authors: Azad Farhan , Fekrmandi Fatemeh , Amin Mody , Goulenko Victor , Belal Ahmed , Plunkett Robert , Fabiano Andrew J. , Fenstermaker Robert Alan , Lipinski Lindsay J. , Torka Pallawi , Cortese Matthew Joseph , Hernandez-Ilizaliturri Francisco J. , Prasad Dheerendra 
Published: June 2023

e14061 Background: Primary or systemic high-grade B-cell lymphoma with secondary central nervous system lymphoma (PCNSL or SCNSL) are currently treated with high-dose methotrexate (HD-MTx) based chemo-immunotherapy regimens with/without whole brain radiation therapy (WBRT). CNS relapse can occur in up to 50% of patients with PCNSL or SCNSL. WBRT has been used as a salvage therapy for those patients. However, long-term neurological toxicities significantly reduce its clinical benefit. Stereotactic radiosurgery (SRS) is the administration of a localized, high dose of ionizing radiation. Limited studies exist exploring SRS as a treatment modality in relapsed/refractory (r/r) PCNSL/SCNSL. Methods: We conducted a retrospective single-center study evaluating the clinical efficacy of SRS in r/r PCNSL/SCNSL. Demographic, clinical, pathological, and treatment characteristics were collected in 29 r/r PCNSL (N=17)/SCNSL (N=12) patients, age ≥ 18 years, who received SRS between 01/2000 and 01/2023. Progression-free survival (PFS) and overall survival (OS) were calculated and reported using Kaplan-Meier analyses and log-rank tests. Results: Baseline characteristics are summarized (Table). The median Karnofsky performance status and Charlson comorbidity index were 70 and 5 respectively. For patients with PCNSL (N=17), the most common prior chemotherapy regimen administered was rituximab (R) in combination with the DeAngelis regimen (N=12), followed by the MATRIX regimen (N=3). In patients with SCNSL, the most common systemic chemotherapy regimen used was R + CHOP (N=9). Few patients received temozolomide (N=2). 5/29 (17%) of patients received WBRT before SRS. The overall response rate (ORR) to SRS in r/r PCNSL was 60% (7 CR and 2 PR). The ORR in r/r SCNSL was 83% (7 CR and 3 PR). The median OS of the overall cohort was 7.0 months (95% CI 5.1-8.9), while the median PFS was 5.0 months (95% CI 1.2-8.7). For patients with PCNSL, the median OS was 10.0 months (95% CI 2.2-17.7), and only 7 months (95% CI 1.8-12.1) for patients with SCNSL. Prior WBRT was associated with worse survival outcomes. Of interest, WBRT was avoided in 24/24 patients (100%). Conclusions: Our data support that CNSL patients can benefit from SRS therapy, with acceptable OS and PFS. In addition, the disease control spared patients from WBRT and therefore, mitigated neurological complications associated with that modality. [Table: see text]
Ventriculoperitoneal shunt and performance status as prognostic factors of overall survival in a retrospective cohort of 78 adult patients with medulloblastoma.
Authors: Trejo-Rosales Raul Rogelio , De Jesus Hernandez Dulce Angelica , Merida Daniela Castro , Silva Godinez Juan Carlos , Otamendi-Lopez Andrea , Remolina Bonilla Yuly Andrea 
Published: June 2023

e14062 Background: Adult medulloblastoma (AM) is a rare disease and represents 1 % of CNS tumors with an incidence of 0.6 per million per year. Usually arise in the cerebellar hemisphere or dorsal brainsteam. Four molecular subgroups are widely recognized and SHH subgroup are common in AM. Treatment options are usually extrapolated from pediatrics experience, and involve surgical resection followed by radiotherapy +/- chemotherapy. Methods: We conducted a retrospective cohort study in patients with medulloblastoma aged ≥18 years at a tertiary institution in Mexico City. We aim to describe clinical and treatment patterns predicting OS and PFS in an adult cohort of medulloblastomas. Kaplan Meier and Log-rank methods were used for survival analysis. Cox proportional hazard model was used for multivariate analysis. Results: Between 2010 and 2022, 78 patients met the criteria for this study. The median age was 28 years (range 18-62) and 64.1% were men. A total of 75.6% had ECOG 0-1. The desmoplastic was the most frequent histologic variant (35.9%). Surgical resection was performed in 93.6% with R0 resection in 49.3% (n=36), while 76.9% (n=61) underwent ventriculoperitoneal shunt (VPS). A total of 70 pts (89.7%) received adjuvant radiotherapy (RT), and the median time to initiation was 18 weeks. Adjuvant and concurrent chemotherapy were received in 53.8% and 12.8%, respectively. One-third of patients did not receive chemotherapy. Vincristine, cisplatin, and cyclophosphamide was the most common combination chemotherapy regimen (28.5%). PFS and OS in the entire cohort were 27.9 months (mo) (95% CI 9.9-45.9) and 124.3 mo (95% CI 52.8-59.8), respectively. OS in patients with ECOG 0-1 was better with 144.8 mo compared with 51.5 mo for ECOG 2-3 (p<0.001). Patients receiving adjuvant RT survived significantly longer (124.3 mo) than patients without radiation (18.8 mo). Other factors associated with survival were time to RT initiation ≤18 weeks vs >18 weeks (not reached vs 59.1 mo, p=0.018) and VPS insertion (144.8 mo vs 46.5 mo, p=0.023). Multivariate analysis identified performance status such as ECOG 2-3 (HR 2.93; 95% CI 1.3-6.6, p=0.009) and VPS (HR 0.39; 95% CI 0.16-0.93, p=0.034) as independent prognostic factors for OS. Conclusions: in this large cohort of Adult Medulloblastoma, we identified ventriculoperitoneal shunt and performance status as the most important factors related with better survival outcomes.
Real world data about stupp platform in the treatment of glioblastoma in a single center of Colombia.
Authors: Cantor Rizo Erick Andres , Segovia Javier , Pino Luis Eduardo , Vargas Henry , Triana Ivan , Murillo Silva John Alejandro , Ospina Serrano Aylen Vanessa 
Published: June 2023

e14065 Background: Glioblastoma cancer is a disease with high mortality reported worldwide. However, in Colombia and Latin America there is a large gap in terms of the information available regarding the characteristics and survival of these patients. Methods: This is an observational, descriptive study of a cohort of patients with glioblastoma cancer who initiated medical treatment at Fundación Santa Fe de Bogotá, a high complexity hospital. We analyzed clinical characteristics, IDH mutation, histology, treatments, progression free survival (PFS), overall survival (OSm) and treatment related complications. We use Kaplan Meier as survival statistic. Results: Twenty patients were included during the 48 months. The average age was 62 years. 65% males, 35% female. IDH mutation detection was performed in 100% of patients, and IDH1 was positive in 20% of the population. Regarding the anatomy location occipital lobe 5%, temporal 20%, parietal 5%, frontal 35%, other locations 35%, ECOG 0-1 were the 100%. Time from start to stupp platform after surgery was 6.1 weeks. All patients received the surgical treatment scheme, later stupp platform followed by temozolamide. In the survival analysis, 15% of patients died during follow-up and 35% progressed to first line. The median overall survival (OSm) 19m, and Progression-free survival (PFS) 14m for the global population. Adjusting survival models for confounding variables, in males the OSm 19 and 15.6m in females. The PDF 15,6m males and 11.8m in females. The OSm in patients with IDH negative 20m, and in the group with IDH1 mutated the OSm has not been reached to 18m of follow-up. Conclusions: Our cohort of patients is similar to the literature reported worldwide, gender may be a predictor of risk. We have good survival times with the stupp platform, rapid access to treatment may be a factor in favor of our good outcomes.
Pharmacokinetics and pharmacodynamics of proposed denosumab biosimilar and reference denosumab in healthy male subjects.
Authors: Vogg Barbara , Poetzl Johann , El Galta Rachid , Fuhr Rainard , Schwebig Arnd , Sekhar Susmit 
Published: June 2023

e14500 Background: Denosumab is a human monoclonal antibody that binds to RANKL, preventing activation of its receptor RANK on the surface of osteoclasts and inhibiting osteoclastic bone resorption. This study was conducted to support demonstration of biosimilarity by evaluating similarity in pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity between GP2411, a proposed Sandoz denosumab biosimilar, and reference denosumab in healthy male subjects. Methods: This double-blind, three-arm, parallel-group, PK and PD study was conducted at two centres in Germany. Participants were randomised (1:1:1) to receive a single 35 mg s.c. dose of either GP2411, EU-authorised reference denosumab, or US-licensed reference denosumab and were followed-up for 39 weeks. A sub-therapeutic dose was chosen since it is more sensitive than therapeutic doses to detect potential PK and PD differences; PK and PD similarity established at the 35 mg dose supports extrapolation to therapeutic doses. The study enrolled 502 healthy male subjects, aged 28–65 years, with a body weight range of 50–90 kg. PK endpoints included the area under the serum concentration-time curve measured from the time of dosing and extrapolated to infinity (AUCinf), or to the last measurable concentration (AUClast), and maximum observed serum concentration (Cmax). PD endpoints were the area under the effect-time curve (AUEC) of the percentage change from baseline (%CfB) in serum carboxy-terminal crosslinked telopeptide of type I collagen (CTX), and CTX and procollagen I N-terminal propeptide (PINP) serum concentration per visit. Results: Overall, 499 healthy volunteers received one of the three treatments. PK and PD similarity was demonstrated between GP2411 and its reference biologic (EU-authorised and US-licensed), as the 90% CIs and 95% CIs of the geometric mean ratios for PK and PD parameters were fully contained within the prespecified equivalence margins [0.80, 1.25]. Changes from baseline to Week 39 in serum concentrations of CTX and PINP were similar between groups. Conclusions: PK and PD similarity between GP2411, a proposed Sandoz denosumab biosimilar, and reference denosumab were demonstrated in healthy male subjects. [Table: see text]
Characterizing the tumor selectivity of oncolytic adenovirus ICVB-1042: Analysis of S-phase induction, viral replication, and cytolytic activity in human primary normal cell types.
Authors: Pokrass Michael , Rosenthal Peter , Messinger Joshua , Rodriguez Ruben , Nowyhed Heba 
Published: June 2023

e14503 Background: Adenoviral-based oncolytic virus (OV) therapeutics include mutations that enable activity in tumor cells and limit toxicity in normal cells. These tumor selectivity approaches often involve mutating viral E1A function or expression; however, such modifications allow viral activity in normal cells or limit anti-tumor potency. ICVB-1042 was engineered with dual modifications in E1A and E4orf6/7, resulting in superior tumor selectivity that does not compromise lytic potency in tumor cells. This improved tumor selective virus minimizes off-tumor activity and promotes robust tumor lysis. Methods: ICVB-1042 was compared to viruses with wildtype E1A and E4orf6/7 and a clinically tested virus with an E1A mutation (ICVB-2006). Viral function and killing were assessed in primary normal human renal (HRE) and bronchial (BrE) epithelial cells in the presence of the inhibitor palbociclib to pharmacologically block S-phase entry via host cell signaling. HRE and BrE were infected with virus and evaluated for indicators of viral toxicity in normal cells. Viral replication was quantified by droplet digital polymerase chain reaction (ddPCR); cell lysis was quantified by WST-1 assay. An S-phase induction assay was developed using an mCherry-Geminin reporter that allows imaging-based quantification of viral-dependent entry to S-phase. Viral activity in cells was compared with and without the CDK4/6 inhibitor using a viral-encoded fluorescent reporter to determine the requirement for host cell proliferation on viral function. Results: ICVB-1042 demonstrated superior protection in normal cells to comparator ICVB-2006 and viruses lacking tumor selectivity modifications. Palbociclib steeply reduced viral reporter gene expression (63-88% reduction), viral replication ( > 10-fold reduction), and cytolytic activity of ICVB-1042, while non-selective viruses were unaffected by this treatment. Non-selective virus infection resulted in 3.3- to 6.1-fold higher levels of S-phase entry compared to ICVB-1042. ICVB-2006 infection resembled non-selective viruses at the level of S-phase induction (3.1- to 3.3-fold above ICVB-1042) and viral reporter gene expression was modestly inhibited by palbociclib (12-31% reduction). Conclusions: The improved tumor selectivity of ICVB-1042 results in protection of normal, non-proliferative cells from viral-mediated toxicity. The conventional approach of ICVB-2006 with a single E1A mutation leaves viral replication and cell death in normal human cells mostly intact. Together, these observations support that ICVB-1042 presents normal cell protection and reduced toxicity risks associated with OV therapy.