bluuebunny/crossref_metadata_2025_split huggingface dataset:
RARE-08. MULTI-INSTITUTIONAL ANALYSIS OF PEDIATRIC RELAPSED/REFRACTORY CENTRAL NERVOUS SYSTEM GERMINOMA
Authors: McGlynn Mary Claire , Abu-Arja Mohammad H , Nagabushan Sumanth , Zaghloul Mohamed Saad , Elhemaly Ahmed , Bertrand Kelsey , Gajjar Amar , Alias Hamidah , Cappellano Andrea , Graham Richard , Baglivo Sofia Jares , Bhadri Vivek , Govender Dinisha , Abdelbaki Mohamed S 
Published: June 2023

Abstract

BACKGROUND
Relapsed central nervous system (CNS) germinomas are rare with no universal agreement regarding management. We explore prognostic factors that may impact the treatment of patients with relapsed CNS germinoma.

METHODS
An international multi-institutional retrospective study of relapsed/progressive CNS germinomas was conducted. Data was summarized using descriptive statistics. Overall survival (OS) was evaluated using Kaplan-Meier and Fischer’s exact test to estimate odds ratios (OR) and 95% confidence intervals (CI).

RESULTS
Analysis included 21 patients (Male 71.4%) with relapsed/progressive germinomas from 7 sites. Median age at diagnosis was 15 years (interquartile range (IQR): 9.9-19) with 5% presenting with metastatic disease. Twelve patients (57.1%) achieved complete remission (CR) after initial therapy. Nineteen children (90.5%) suffered relapse. One (4.8%) suffered progression. The median time from diagnosis to relapse/progression was 21 months (range: 10-56 months) with 90.5% occurring within 24 months. 19 (90.5%) underwent chemotherapy, 9 (42.9%) bone marrow ablative therapy (HDCx), and 13 (61.9%) radiotherapy. At last follow-up, 88.9% of HDCx and 92.3% of radiotherapy recipients were alive. Of patients receiving radiation, 45% received whole ventricular irradiation, 25% craniospinal irradiation, and 5% focal irradiation (remainder unreported). Eleven children (52.4%) achieved CR after relapse/progression therapy and 16 (76.2%) were alive at last follow-up. Median time to last follow-up was 39 months (IQR: 18.43–89.50). Re-irradiation at relapse (OR=16, 95% CI: 1.27-200.9) and achieving complete response (CR) at relapse/progression (OR=4, 95% CI: 1.04-1.78) were associated with improved OS. CR after initial therapy (OR=0.857, 95%CI: 0.11-6.62) and HDCx at relapse/progression (OR=4, 95%CI: 0.36-44.13) were not associated with improved OS.

CONCLUSIONS
Relapsed CNS germinomas are radiosensitive and salvageable by re-irradiation at relapse. This ongoing multi-institutional study will contribute to existing knowledge about relapsed/progressive CNS germinomas and inform prospective clinical trials to improve outcomes for children with relapsed/progressive disease.
OUTC-02. CASE SERIES OF HYPERMUTATED PEDIATRIC CNS TUMORS
Authors: Parisi Rose , Horowitz Emma , Patel Roshal , Rood Gavrielle , Bowden Acacia , Turco George , Korones David , Andolina Jeffrey , Comito Melanie , Barth Matthew , Weintraub Lauren 
Published: June 2023

Abstract
In pediatric central nervous system (CNS) tumors, high tumor mutational burden (TMB) (≥3 mutations/megabase (mut/Mb)) has been correlated with lower overall survival and higher rates of progression as compared to low TMB tumors (&lt;3 mut/Mb). This study is the first to examine a subset of pediatric CNS hypermutated tumors (≥10 mut/Mb) in comparison to high TMB tumors. We conducted a retrospective analysis of 121 pediatric patients (61 female (50%)) with a median age of 9 years diagnosed with a primary CNS tumor (high TMB, N=34; low TMB, N=55) at four academic medical centers from 2008 to 2021. Hypermutated tumors (N=3) were exclusively high grade tumors; subtypes were ependymoma, medulloblastoma, and oligodendroglioma. Hypermutated tumors had an average TMB of 65 mut/Mb (range=11-132 mut/Mb). Most of the hypermutated tumors had TP53 mutations (N=2; 67%) as compared to 29% of high TMB patients (N=12). Sixty-seven percent of patients with hypermutated tumors experienced tumor progression (N=2) as compared to 44% (N=15) of patients with high TMB tumors. Average time to progression was 2.4 years in hypermutated tumors and 1.4 years in high TMB tumors. No patients with a hypermutated tumor experienced a death event, as compared to 41% (N=14) of patients with high TMB. Although we report a small subset of hypermutated pediatric CNS tumors, this multi-institution case series suggests that hypermutated tumors may be associated with higher rates of progression, slower time to progression, and lower mortality as compared to high TMB tumors. Future research with a larger population of hypermutated tumors is needed to better characterize outcomes to optimize treatment for this subset of patients.
OUTC-05. DIFFERENCES IN FACTORS INFLUENCING SURVIVAL IN CHILDHOOD AND ADULT CNS MALIGNANCIES
Authors: Matharoo Jashanjeet , Dux Hayden , Broaddus William 
Published: June 2023

Abstract
Socioeconomic factors such as income and community type have shown to correlate with outcomes in neuro-oncologic care. In pediatric populations, however, fewer conclusions have been drawn on the effects of factors such as race, gender, and insurance status on survival due to the relative rarity of such cases. This analysis utilizes the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) program database to determine differences in factors influencing survival in both pediatric and adult CNS malignancies. From the SEER Research Nov 2020 (1975-2018) dataset, 29865 patients with malignant CNS tumors (identified by ICD-0-3 code) diagnosed between 1990-2018 and directly causing patient demise were selected and data were collected on age at diagnosis, sex, race, median household income (in 2019 USD), community type (rural-urban continuum), and survival (in months). This cohort was separated into pediatric (ages 0-19, n = 1509) and adult (ages 20 and above, n = 28356) subgroups and independent survival analysis was conducted by income, community type, sex, race, and decade of diagnosis. Kaplan-Meier curves were visualized for each comparison. Log rank analysis of survival in the pediatric cohort showed greater mortality in females (p = 0.0224) and in the most recent decade (p &lt; 0.0001). The same analysis in the adult cohort showed greater mortality in lower income groups, more rural community settings, females, patients categorized as White, and in the most recent decade (p &lt; 0.0001 for all comparisons). Unlike in the adult population, income, community setting, and race were not associated with significant differences in survival in the pediatric population, prompting further investigation into healthcare delivery differences between pediatric and adult populations. Further study should focus on the cause of these discrepancies to improve equity in neurosurgical care.
OUTC-06. BEST PRACTICES FOR THE SUCCESSFUL ADMINISTRATION OF COMBINATION METRONOMIC ANTI-ANGIOGENIC AND INTRAVENTRICULAR THERAPY
Authors: Burnside Kasey L , Margol Ashley S , O’Halloran Katrina , Robison Nathan J , Rushing Teresa , Davidson Tom B , Rangan Kasey , Waters Kaaren 
Published: June 2023

Abstract

BACKGROUND
Combination metronomic anti-angiogenic and intraventricular therapy incorporates a customized administration of a five-drug oral antiangiogenic regimen with intravenous bevacizumab and intraventricular chemotherapy and is an effective treatment regimen for children with recurrent central nervous system embryonal tumors. This treatment can be administered while maintaining quality of life and avoiding severe side effects through personalized therapy schedules; however, dosing modifications, available dosage formulations, and complexity of medication administration creates challenges for families and clinical staff.

METHODS
A retrospective chart review was completed on 11 patients who received this treatment with various combinations of oral medications (thalidomide, etoposide, cyclophosphamide, celecoxib, and fenofibrate), intravenous (IV) medication (bevacizumab), and intraventricular chemotherapy (cytarabine, etoposide, and topotecan). We implemented successful nursing interventions, family education, variable scheduling options, dosage formulation selections, and innovative oral and intraventricular administration techniques.

RESULTS
Patients were able to successfully receive therapy for an average of 14 months and no patient came off for toxicity. Treatment was generally well-tolerated, with most toxicities being hematologic or gastrointestinal in nature.

CONCLUSION
Education, innovative dosing schedules, recognition of potential side effects, and medication administration allow for successful administration of this complex therapy.
OUTC-07. ANALYZING PREDICTORS OF LOSS TO FOLLOW-UP AS SEEN AMONG YOUNG SURVIVORS OF CENTRAL NERVOUS SYSTEM TUMORS FOR QUALITY IMPROVEMENT INTERVENTIONS AT DANA FARBER CANCER INSTITUTE
Authors: Cooney Tabitha , Tabatneck Mary , Stone Amelia 
Published: June 2023

Abstract
At Dana Farber Cancer Institute, children and young adults who have completed treatment for central nervous system tumors visit the Pediatric Neuro-Oncology Outcomes Clinic (“Empower”) for survivorship visits. By attending these long-term clinic visits, survivors can receive multidisciplinary services and undergo monitoring for disease recurrence. We used descriptive statistics and chi-square tests to investigate the relationship between loss to follow-up and sociodemographic factors among Empower patients. We reviewed medical records to gather data on 200 patients who had visited the clinic between 1-1-2015 and 1-1-2020, extracting information about sex, zip code, diagnosis, treatment received, and insurance type (private vs. public). We then indicated whether each patient had been “lost to follow-up,” defined as not returning to the clinic for &gt;1,000 days after the recommended follow-up date. Among the 200 patients reviewed, 46 (23%) were lost to follow-up and 154 (77%) were not lost to follow-up. With respect to race and ethnicity, individuals identifying as Black, Asian, Middle Eastern, Native Hawaiian or Pacific Islander, Hispanic or Latino, or “Other” were more likely to be lost to follow-up than patients who exclusively identified as White (21% versus 39%; p=0.036). Additionally, individuals who were lost to follow-up were more likely to have been treated for low-grade gliomas as opposed to other CNS tumors (30% versus 13.6%; p=.015). Sex, the use of chemotherapy and radiation, and insurance type did not have a significant association with loss to follow-up. An analysis of the relationship between median household income and loss to follow-up is pending. The results imply that there is a significant association between non-white race, Hispanic or Latino ethnicity, a diagnosis of low-grade glioma, and loss to follow-up. The continuation of this study can provide the groundwork for interventions targeted at supporting patients who are at an increased risk of loss to follow-up.
OUTC-09. PEDIATRIC LOW GRADE GLIOMA SURVIVORS’ NEED FOR SURVIVORSHIP CARE: ‘ENGAGE’ A MULTIDISCIPLINARY, E-HEALTH INTERVENTION
Authors: McLoone Jordana , Hamayun Mashaal , Nagabushan Sumanth , Signorelli Christina , Wakefield Claire , Johnston Karen , Bell Rachael , Cohn Richard 
Published: June 2023

Abstract
Higher survival rates for children diagnosed with low-grade gliomas (LGG), compared to other brain cancers, often limit the survivorship resources afforded this cohort, despite potential long-term physical, functional and psychological impacts. We conducted a two-phase program of research, first evaluating LGG survivors’ need for support during the survivorship phase, followed by the development and pilot evaluation of a multidisciplinary, telehealth, survivorship program. Phase 1: We conducted a retrospective cohort study of children aged 0-16 years at diagnosis, diagnosed between 2000-2015, assessing psychosocial impact and quality of life. Phase 2: We developed ‘Engage Brain’, a multidisciplinary, telehealth program, designed to improve medical and psychosocial outcomes for childhood cancer survivors throughout their lifespan. Key components of Engage’s design include distance-delivered care to ensure access for all survivors irrespective of whether they live close to a tertiary, survivorship center; hospital-based expertise integrated with local, primary care services to ensure a model of care which is sustainable long-term; nurse-led care providing tailored education to encourage adoption of a prevention-focused healthy lifestyle to mitigate survivors’ personal risk and reduce ongoing costs to the individual and healthcare system; psychosocial focus, incorporating allied health staff (psychologist/social worker) as an integral aspect of care. Phase 1: 45 survivors participated (36% female, mean age 14.8 years, average 7.5 years post-treatment). Survivors reported high levels of anxiety (23%), depression (14%), fatigue (62%). Phase 2: 30 LGG survivors completed Engage Brain intervention (50% female, mean age 21 years, average 11.5 years post-treatment). 64% uptake, 10% attrition. Most (78%) of participants ‘agree’-‘greatly agree’ that Engage Brain provides ‘high-quality survivorship care’ and ‘help accessing survivorship care’. This program of research illustrates the long-term needs of LGG survivors, despite their lower risk status compared to other brain cancers, and the feasibility of providing a multidisciplinary, telehealth intervention to support them.
OUTC-11. RACE AND AGE ARE ASSOCIATED WITH ICD-10 DIAGNOSES IN THE POST-OPERATIVE PERIOD FOR PEDIATRIC PATIENTS WITH PRIMARY BRAIN TUMORS UNDERGOING NEUROSURGERY
Authors: Montgomery Canada , Plisiewicz Alexa , Zhao Chao , Yan Ying , Phillips Charles , Lehmann Kaitlin , Storm Phillip , Madsen Peter , Kline Cassie 
Published: June 2023

Abstract

BACKGROUND
Disparities in pediatric cancer care and outcomes are known to exist. This work evaluates the relationship of race, ethnicity, and social determinants of health (SDoH) on the post-operative neurosurgical course of pediatric neuro-oncology patients in a single-institution.

METHODS
Retrospective data were collected on patients undergoing initial neurosurgery for a primary central nervous system (CNS) tumor between May 2011 and April 2021. Newly attributed ICD-10 codes in the 30-day post-operative period were collected. Descriptive statistics were used to evaluate demographics, geographic region of residence, and insurance type. Logistic regression was performed to estimate the association between covariates and 30-day readmission as well as ICD-10 diagnoses that can complicate the postoperative course including cardiac/respiratory, bleeding, infection, wound, hardware implantation, and neurologic conditions. Linear regression was used to measure association of covariates and length of stay (LOS).

RESULTS
A total of 836 patients, median age 10.0 years, were included (n=368 females, 44%). Patients were predominantly white (69%) and non-Hispanic/Latino (88%). White (OR [95% CI] 0.55 [0.33,0.90], p=0.02), Native American/Indian (0.25 [0.07,0.89], p=0.03), and multiracial (0.24 [0.08,0.68], p=0.01) patients were significantly less likely to have new ICD-10 codes compared to Black patients. White patients trended toward shorter LOS (p=0.06) compared to Black patients. Younger patients were significantly more likely to have newly reported ICD-10 codes (0.95 [0.92,0.97], p&lt;0.001), increased LOS (r=-0.59 [-0.87,-0.32], p&lt;0.001), and 30-day readmission (0.81 [0.72,0.89], p&lt;0.001). Sex, ethnicity, insurance type, and region had no significant association with outcomes. Income level analyses are ongoing.

CONCLUSION
Non-black patients were less likely to have new ICD-10 diagnoses reported after surgery for primary CNS tumors. Older age was a protective factor against new post-operative diagnoses, increased LOS, and mortality. More research is necessary to understand the relationship between race, ethnicity, SDoH and post-operative risk including possible mechanisms of interaction across variables.
OUTC-12. BLACK IN CANCER: EMPOWERING AND ENCOURAGING FUTURE BLACK CANCER LEADERS WHILST REDUCING CANCER DISPARITIES THROUGH EDUCATION AND ADVOCACY
Authors: Bonner Sigourney 
Published: June 2023

Abstract
From its inception in 2020, Black in Cancer has been modelling an action-oriented approach to improving representation across the cancer community. Black in Cancer (BIC) was founded during the racial justice protests that swept across the globe in the midst of a number of Black professionals aiming to promote visibility and sharing of resources within their respective groups leading to “Black in X” communities on social media and in particular twitter. This network was required in the cancer community with Black cancer researchers, clinicians and patient advocates being underrepresented and Black patients underserved.
Black or African American workers make up 12% of the U.S. working population but represent just 9% of STEM workers. Dissected even further, only 3% of medical oncologists are Black and training programs such as oncology fellowships have minimally increased between 2006 and 2018. For researchers, this disparity is even more prominent, as only 1% of all professors in biology at U.S.institutions are Black and just 0.6% in the UK. Studies show that Black researchers are about 55% less likely to receive NIH funding than white researchers. Several studies from AACR and Cancer Research UK show that Black patients are diagnosed at a later stage, with more aggressive cancers and have a higher mortality rate. Our organisation has two main initiatives to tackle these challenges, through our
Cancer Awareness Project (CAP)and the Mentorship and Outreach Program (MOP). These programmes have delivered $2 million in funding for Black cancer researchers at the postdoctoral level and above, and have also supported almost 40 undergraduate students through our mentorship program. Our CAP initiative has delivered a number of informational sessions to the community in how to identify symptoms, diagnosis pathways and how patients can be informed and empowered about their healthcare decisions.
HGG-11. APPLICATION OF SHUNT IN PEDIATRIC DIFFUSE INTRINSIC PONTINE GLIOMA COMPLICATED WITH HYDROCEPHALUS: A 10-YEAR EXPERIENCE FROM A SINGLE CENTER
Authors: Cai Linbo , Lai Mingyao , Li Juan , Ai Ruyu 
Published: June 2023

Abstract

OBJECTIVE
Currently, there is no unified treatment protocol for pediatric diffuse intrinsic pontine glioma with hydrocephalus. The present study aims to explore the clinical characteristics and the best intervention modality for pediatric diffuse intrinsic pontine glioma with hydrocephalus.

METHODS
The detailed data of children with diffuse intrinsic pontine glioma admitted to the Department of Pediatrics of Guangdong Sanjiu Brain Hospital from January 2010 to December 2021 were retrospectively analyzed. The effect of radiotherapy and shunt on the prognosis of pediatric diffuse intrinsic pontine glioma complicated with hydrocephalus was evaluated.

RESULTS
165 children with DIPG aged ≤18 years were included in the analysis, of whom 9 (5.5%) had mild ventricular dilatation, 48 (35%) had hydrocephalus, and 11 (22.9%) underwent cerebrospinal fluid shunting, of whom 10 (90.9%) underwent ventriculoperitoneal shunt and 1 (9.1%) underwent endoscopic third ventriculostomy. After shunt and radiotherapy, 53 cases of hydrocephalus could be evaluated, of which 37 patients (69.8%) were significantly relieved, and 16 (30.2%) were not. 99 children had tumor progression after treatment, including 41 cases (41.4%) with hydrocephalus and 5 cases (12.2%) with ventriculoperitoneal shunt. A total of 138 children were included in the survival analysis, which revealed that hydrocephalus, mild ventricular dilatation, and no ventricular abnormality had no effect on the prognosis (p=0.944). The treatment of hydrocephalus at the initial diagnosis did not affect the prognosis, p=0.405. The median survival of the hydrocephalus remission group post-radiotherapy was 12 months, and 8 months for the non-remission group, p=0.042. The median survival was 20 months in the shunt group and 8 months in the untreated group (p=0.005).

CONCLUSIONS
Asymptomatic ventricular enlargement in pediatric diffuse intrinsic pontine gliomas does not require surgical intervention. Hydrocephalus remission post-radiotherapy is a favorable prognostic indicator. Cerebrospinal fluid shunt could improve the prognosis of children with hydrocephalus when the tumor progresses post-radiotherapy.
HGG-16. COMPARATIVE ANALYSIS OF AUTOPHAGY IN DRUG RESPONSES AND AGGRESSIVE BEHAVIOR OF ADULT VERSUS PEDIATRIC GLIOMA CELL LINES
Authors: Yenidogan Irem , Peker Nesibe , Deveci Gamze , Aygun Bera , Kirmizi Dondu , Al Nathalie , Asarcikli Fikret , Oflaz Sozmen Banu , Akyoldas Goktug , Kulac Ibrahim , Solaroglu Ihsan , Gozuacik Devrim 
Published: June 2023

Abstract
Central nervous system tumors are the most common solid cancer and a leading cause of cancer-related deaths in children. Glioma is the most challenging pediatric CNS tumor with therapy resistance and poor prognosis in pediatric patients. Although histopathological analyses revealed similarities with adult brain glioma, emerging evidence suggests that the deregulated molecular pathways in pediatric glioma (p-GM) are different from that of adults. Autophagy, a cellular clearance system and a drug resistance mechanism, has been implicated in glioma progression, invasion, and relapse, yet its role in pediatric patients is not well documented. In this study, we compared the autophagic capacity of adult versus p-GM cell lines and evaluated the effect of autophagy manipulation on drug responses. In addition, migration, extracellular matrix invasion ability, and the metabolism of pediatric and adult gliomas were compared and the contribution of autophagy to the aggressive phenotype was evaluated.
HGG-21. ABERRANT SPLICING OF CLK1 IN PEDIATRIC HIGH-GRADE GLIOMAS DISRUPTS KEY ONCOGENIC TRANSCRIPTIONAL PROGRAMS
Authors: Naqvi Ammar , Ennis Brian , Corbett Ryan , Lahiri Aditya , Geng Zhuangzhuang , Kin Run , Gaonkar Krutika , Rathi Komal , Conkrite Karina , Seghal Priyanka , Hayer Katharina , Kraya Adam , Foster Jessica , Madsen Peter , Thomas-Tikhonenko Andrei , Storm Phillip , Resnick Adam , Rokita Jo Lynne 
Published: June 2023

Abstract
While the majority of somatic DNA coding alterations in pediatric brain tumors have been profiled, studies exploring transcriptional mechanisms remain underexplored. We systematically characterized aberrant splicing in primary tumors of seven broad histologies of pediatric brain tumors. We obtained RNA-seq data (n = 792) from the Open Pediatric Brain Tumor Atlas and integrated rMATs splice event calls with UniProt Knowledgebase to quantify and prioritize differential alternative splicing events with proteomic potential. We identified three splicing-driven biological clusters and found pediatric high-grade gliomas (pHGGs) to be uniquely heterogeneous, spanning all three clusters. We also discovered that tumors with high splicing burden (SB) had significantly worse overall survival than tumors with low SB (p &lt; 1x10-4). Furthermore, pHGGs (n = 154) displayed the greatest splicing heterogeneity with 20,620 exon splicing aberrations (pval/FDR &lt; 0.05) in 3,294 genes that resulted in a gain or loss of known functional sites. We prioritized targetable kinases and found that CDC-like kinase 1 (CLK1), a known modulator of master splicing regulators, exhibited significantly increased exon 4 inclusion (p &lt; 0.05, ΔPSI &gt;= |.20|), and subsequent gain of two phosphorylation sites, in tumors compared to matched non-tumor tissue. Exon 4 inclusion was significantly correlated with increased CLK1 expression (r = 0.57, p = 7.8 x10-9), which we posit results in hyper-activity of CLK1 and aberrant splicing of its targets in these tumors. Furthermore, predicted CLK1 gene targets (n = 101) were enriched for cancer-related pathways, such as DNA repair (odds ratio &gt; 2, p &lt; 0.005). In summary, we describe aberrant splicing in pHGGs as an alternative mechanism that could drive tumorigenesis. Future work will focus on molecular validation and therapeutic targeting of CLK1 in available pHGG models, potentially opening new therapeutic strategies in children with brain tumors.