bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-11. Detection of genetic and epigenetic alterations in Liquid Biopsies from pediatric brain tumor patients
Authors: Fischer Tom T , Maaß Kendra K , Puranachot Pitithat , Finster Agnes M E , Mieskolainen Markus , Schad Paulina S , Sill Martin , Rosing Fabian , Wedig Tatjana , Schwarz Nathalie , Iser Florian , Meyer Jochen , Sahm Felix , Brors Benedikt , Haapasalo Hannu , Pfister Stefan M , Haapasalo Joonas , Pajtler Kristian W , Nordfors Kristiina 
Published: June 2022

Abstract
BACKGROUND: Liquid biopsies (LBs) hold great promise as a non-invasive method for tumor detection and disease monitoring. Their application in pediatric neuro-oncology patients has been challenging due to the blood-brain barrier limiting the amount of circulating tumor DNA (ctDNA) and low volumes of cerebrospinal fluid (CSF) and serum samples. Here, we assessed the feasibility of LBs in a pediatric brain tumor cohort (n=12 patients) by adapting pre-analytical protocols to low cell-free DNA (cfDNA) input and bioinformatic pipelines for genome-wide analyses. METHODS: Genomic DNA isolated from tumor tissues, including medulloblastoma (n=6), ependymoma (n=4), low-grade glioma (n=1), and choroid plexus papilloma (n=1), and cfDNA isolated from matched CSF and serum samples were subjected to low-coverage whole genome sequencing (lcWGS) and the EPIC DNA methylation array. For methylation analyses, samples were prepared using both traditional bisulfite- and recently developed enzymatic-based methylation conversion. Molecular tumor (sub)type predictions were performed using the Heidelberg Brain Tumor Classifier. RESULTS: lcWGS revealed tumor-specific copy number variations (CNVs) in both CSF and serum samples. The detection rate of tumor-specific CNVs (median 92% vs. 23%) and the ctDNA fraction (median 31% vs. 1.5%) were higher in CSF vs. serum samples. Bisulfite-converted as well as enzymatically converted tumor DNA and cfDNA samples could be readily analyzed using the Heidelberg Classifier. In comparison to bisulfite-based conversion, enzymatic-based conversion improved the quality of methylation analyses for minimal input cfDNA samples. CONCLUSIONS: Our results highlight the feasibility of liquid biopsies from both CSF and serum in brain tumor patients. In contrast to CNV-based tumor detection from serum samples, ctDNA analysis from CSF allowed a more comprehensive genetic and epigenetic profiling which is expected to assist in less-invasive tumor classification, identification of drug targets, or the investigation of tumor evolution. Altogether, this study provides the rationale for further implementation of LBs in pediatric neuro-oncology.
LINC-04. Optic pathway gliomas in children: an 18-year experience in a middle-income country
Authors: Ramirez-Melo Jorge , Moreira Daniel , Orozco-Alvarado Ana , Sánchez-Zubieta Fernando , del Campo Regina Navarro-Martín 
Published: June 2022

Abstract
BACKGROUND: Optic pathway gliomas (OPGs) have favorable survival outcomes, but can have significant morbidity, from the tumor or from its treatment. This retrospective study sought to describe the clinical presentation and outcomes of children with OPGs at a tertiary center in a middle-income country. METHODS: Patients younger than 18 years diagnosed with OPGs between 2002-2020 at the Hospital Civil de Guadalajara in Mexico, were included. Survival analyses and logistic regression were used to determine risk factors for progression. RESULTS: Thirty patients were identified with a median age of six years. Common clinical characteristics at presentation included: visual accuracy impairment (40%), headache (23.3%), nystagmus (20%), endocrine disturbances (16.6%), and diencephalic syndrome (13%). Neurofibromatosis-1 was present in 23.3% of the patients. Eight patients underwent resection at diagnosis, 7 of them had secondary complications. One died during surgery due to catecholamine-resistant shock, and the other developed neuro-infection and died due to septic shock after surgery. Five children developed neurological or endocrine sequelae. Fifteen total patients received chemotherapy as their first line treatment. The 5-year progression-free survival was 77.9±10% and overall survival was 89.5±5%. Patients who received chemotherapy or targeted therapy as the first line of treatment had higher PFS compared to those who received other therapies (p=0.03). The patients who received surgery as first-line treatment had a 3.1 times greater risk of achieving a Lansky/Karnofsky score of fewer than 90 points 6 months after diagnosis (p=0.006). Ten patients had pre- and post-treatment ophthalmologic assessment, either visual acuity or visual evoqued potentials. Five had no changes and 5 showed improvement after treatment. CONCLUSIONS: These results show inferior outcomes compared to high-income countries, influenced importantly due to morbidity after surgical resection. These data can be used to prospectively optimize treatment at our institute and other middle-income countries through a multidisciplinary neuro-oncology team.
LINC-05. Successful response to bevacizumab/irinotecan/temozolomide in a progressive choroid plexus carcinoma: A case report
Authors: del Campo Regina Navarro-Martin , Pozos-Ochoa Ivan , Bañuelos-Gallo David , Sanchez-Zubieta Fernando , Orozco-Alvarado Ana L 
Published: June 2022

Abstract
Choroid plexus carcinomas (CPC) are a rare type of aggressive pediatric brain tumors with poor survival rates, and no standard curative therapy after relapse. We report the case of a 1-year-oldmale, with a right lateral ventricular CPC and disseminated leptomeningeal disease. First line therapy was an initial surgery aborted due to hemorrhage and a second near total resection. After the second surgery six cycles of ICE regimen were applied. The MRI after primary therapy showed progression with a new lesion located on the optic pathway and leptomeningeal disease. At this point a second line therapy consisting of Bebacizumab 10 mg/kg and Irinotecan 125 mg/kg every 2 weeks and Temozolamide 150 mg/m2 every 4 weeks was given. He received up to 24 cycles. His imaging demonstrated 80% primary tumor reduction and improvement of leptomeningeal disease. This treatment gave him the time to turn 3 years old to receive 3D conformational craniospinal radiotherapy as follows: spine 24Gy, overdose 27 Gy to tumor bed and cranial for a total dose 51 Gy. The patient is now 19 months from the end of treatment with stable disease. He is clinically well, with good performance status (Lansky 100%) and attending school. The relevance to present this case is to highlight a safe and effective treatment for a relapsed CPC since there is not a curative therapy for these children.
LINC-08. Neuro-Oncology tumor board – one-year experience of international collaboration
Authors: Shatara Margaret , Cantor Evan , Meyer Ashley , Ogle Andrea , Hofmann Kimberly , Green Tammy , Beck Mary , McHugh Michele , Brossier Nicole , Cluster Andrew , Mian Ali , Dahiya Sonika , Abdelaziz Zeyad M , Fadel Shady , Mobark Nahla , AlHarbi Musa , AlJaouni Soad , Aljunaid Abrar , Said Waleed , El-ayadi Moatasem , Mahmoud Madeha , Al-Battashi Abeer , Chabchoub Imène , Khalifa Nisreen , Dengler Nora , Driever Pablo Hernáiz , Del Río Nicolás Rojas , Dembowska-Bagińska Bozenna , Perek-Polnik Marta , Skoczeń Szymon , Dholaria Hetal , Nagabushan Sumanth , Oliveira Milena , Hirbe Angela C , Armstrong Amy E , Limbrick David , Gutmann David H , Abdelbaki Mohamed S 
Published: June 2022

Abstract
BACKGROUND: The management of childhood central nervous system (CNS) tumors is complex and often faces numerous challenges in low- and middle- income countries (LMICs), including delayed diagnosis and limited treatment resources. Twinning initiatives between LMICs with high- income countries are feasible and proven to be highly effective at exchanging skills and expertise to improve diagnosis, treatment and care for children with brain tumors. METHODS: A monthly multidisciplinary international pediatric neuro-oncology tumor board via zoom videoconferencing was established in January 2021. This effort is a collaboration between Washington University School of Medicine, in St. Louis, Missouri, USA and nine international sites. Given the significant contributions of this international effort, it has since grown to include 20 institutions and cancer centers from 12 countries in the Middle East, Europe, Australia and South America. RESULTS: As of January 2022, we have held 11 tumor boards, 35 cases were reviewed, and have had 320 experts attend from several specialties – neuro-oncology, neurology, neurosurgery, neuroradiology and neuropathology. A multidisciplinary team of physicians reviewed each case and recommendations were given accordingly. We also started a quarterly neurofibromatosis (NF) meeting focused to leverage the expertise of dedicated specialists in the NF center. Two NF-focused meetings took place since establishing the program, and total of five cases were discussed. CONCLUSION: Virtual videoconferencing promotes a multi-disciplinary approach for the management of pediatric CNS tumors, and it allows access for medical expertise. We anticipate the current initiative will also provide a platform for future international research collaborations and deliver the optimal medical care for neuro-oncology patients globally. Multiple potential collaborative projects are currently underway.
LINC-16. Factors Associated with Delayed Diagnosis Among Filipino Pediatric Brain Tumor Patients: A Retrospective Review
Authors: Orduña Patricia , Lubaton-Sacro Cheryl Anne 
Published: June 2022

Abstract
BACKGROUND: Delayed diagnosis is observed greatest among pediatric brain tumors compared to other childhood malignancies. Several factors have been found to influence delay. OBJECTIVE: To determine delayed diagnosis measured by the prediagnostic symptomatic interval (PSI) among Filipino pediatric brain tumor patients and identify associated factors. METHODS: Data was collected retrospectively on pediatric brain tumor patients of Philippine General Hospital from 2015-2019. PSI was calculated. Demographic and clinical data were presented using descriptive statistics. Bivariate and linear regression analyses were used to determine factors. RESULTS: The median overall PSI was 80.5days. The median interval from symptom onset to first physician consult was 22days. The median interval from first consult to subspecialty referral was 23.5days. Majority presented with 2 symptoms at onset (42.3%) and during first physician consult (36.2%). Upon subspecialist referral, 52% have ≥4 symptoms. Most patients (68.4%) consulted with a pediatrician. Most were diagnosed with another condition prior to brain tumor diagnosis. Longer PSI was significantly associated with older age (p=0.005), tumor location (p=0.009), tumor grade (p&lt;0.001), and more physicians consulted prior to subspecialist referral (p=0.001). Significant predictors of delayed diagnosis were supratentorial tumors (4-month delay, p=0.014), and those presenting with seizures (11-month delay, p=0.002), poor school performance (1-year delay, p=0.008), behavioral changes (1.3-year delay, p=0.033), and secondary amenorrhea (3-year delay, p=0.021). Predictors of earlier brain tumor diagnosis include posterior fossa tumors (p=0.041), malignant tumors (p=0.002), and vomiting (p=0.020). CONCLUSION: Delayed diagnosis among Filipino brain tumor patients is associated with age, tumor characteristics and symptoms that are uncommon in this condition. This emphasizes the need for first contact physicians to be aware about these symptoms, and keep a diagnosis of brain tumor as a differential. This, coupled with a detailed history, accurate neurologic examination and early subspecialist referral may lead to earlier diagnosis and treatment for pediatric brain tumor patients.
LINC-17. A single center retrospective analysis of pediatric intracranial choroid plexus carcinoma in Beijing
Authors: Li Miao , Sun Yanling , Du Shuxu , Zhang Jin , Wu Wanshui , Sun Liming 
Published: June 2022

Abstract
Objective: To explore the clinical characteristics and outcome in children with intracranial choroid plexus carcinoma in Beijing. Methods: We retrospectively analyzed 13 children with pathologically confirmed diagnosis of choroid plexus carcinoma between January 2017 and December 2021. They were treated with surgical resection followed by adjuvant therapies. Results: Male/female ratio=0.625(5:8). The median age at diagnosis was 1.2 years (range, 6 months to 9.8 years) with 9 cases &lt; 3 years of age. Gross total resection was achieved in 12 cases (92.3%), and subtotal resection in 1 case. Seven patients received only adjuvant chemotherapy according to CPT-SIOP-2009 protocol, and 6 patients underwent radiotherapy with combined chemotherapy. Six patients developed a recurrence, and 4 cases died at last follow-up. Among 9 patients alive, 7 cases attained CR, 1 PR and 1 SD.The 5-year progression-free survival (PFS) and overall survival (OS) were (64.8±14.3) % and (68.4 ± 13.1) %, respectively. The survival of children treated under both irradiation and chemotherapy were higher than chemotherapy only (P&lt;0.05). The cases &lt; 3 years of age had worse survival than those ≥3 years (P&lt;0.05), and the 4 cases died were all younger than 3 years old. Conclusions: Choroid plexus carcinoma is a rare and malignant brain tumor, and affects mainly younger children in our center. Surgical resection is the mainstream treatment. Adjuvant radiotherapy with combined chemotherapy and patients older than 3 years old tend to have better survival. Keywords: Choroid plexus carcinoma; Therapy; Survival.
LINC-19. Epidemiological Profile And Management Trends in Pediatric Brain Tumour Patients – 15 Year Experience From a Tertiary Neuro-Oncology Centre In South Asia
Authors: Singh Vikas , Pathiyal Rajesh , Shetty Prakash , Sridhar Epari , Chinnaswamy Girish , Gupta Tejpal , Moiyadi Aliasgar 
Published: June 2022

Abstract
INTRODUCTION: Brain tumour in pediatric age group are the most common solid tumour. Commonly occurring tumours include astrocytomas, medulloblastoma and ependymoma. Astrocytoma and medulloblastoma are common in Europe as compared to the Asian countries. AIM: To study the epidemiological profile and trends in management of pediatric brain tumor patients treated at a tertiary Neuro-oncology center. MATERIALS AND METHODS: This a retrospective audit of a prospectively maintained neurosurgical database from January 2007 to December 2021. All pediatric cases (&lt; 18 years) operated by the neurosurgical oncology unit during the study period were included for analysis. CSF diversions and non oncologic surgical procedures were excluded. Demography, referral pattern, surgical and pathological variables of these patients was analyzed from the database and electronic medical records. Patients with missing data were excluded from analysis. RESULTS: 668 patients underwent oncologic surgical procedures. There was a male preponderance (60%) and 35% of children were in the age group of 5-11 years. Hospital received maximum referral from the parent city and state (46%) followed by north india (21%). Supratentorial tumours (52 %) were seen more commonly as compared to infratentorial tumours (39 %). Astrocytoma (31 %) and embryonal tumours( 25 %) were the common histological types. On subset analysis, both astrocytic (70%) and embryonal tumours (57%) were more common in children more than five years. Intraoperative neuromonitoring, intraoperative ultrasound and navigation were used during the surgical procedures as necessary. CONCLUSION: This study is one of the largest single institution analysis of pediatric brain tumours demonstrating trends in the demographic, surgical and pathological variables over 15 years and the observed pattern is similar to published literature from Indian subcontinent.
LINC-23. Factors influencing outcomes of older children with Medulloblastoma over 15 years in Peru, a resource limited setting
Authors: Diaz-Coronado Rosdali , Reinecke James B , Stanek Joseph R , Finlay Jonathan L , Hernandez-Broncano Eddy , Chavez-Paredes Sharon , Miranda-Tunque Yesenia , Heredia-Zelaya Adela , Casavilca-Zambrano Sandro , Garcia-Corrochano Pamela , Ojeda-Medina Luis , Orrego-Puelles Enrique , Torres-Malca Ebert , Sernaque-Quintana Raymundo , Quispe-Valverde William , Garcia-Leon Juan , Osorio Diana S 
Published: June 2022

Abstract
BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with Medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru. METHODS: Between 1997-2013, data from 103 children older than three years with Medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997 – 2008 and 2009 – 2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, while prognostic factors were determined by univariate analysis (log-rank test). RESULTS: Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The five-year OS was 62% (95% CI: 53 – 74%) while EFS was 57% (95% CI: 48 – 69%). The variables adversely affecting survival were anaplastic histology [compared to desmoplastic; OS: HR=3.4, p=0.03], metastasis [OS: HR=3.5, p=0.01; EFS: HR=4.3, p=0.004], delay in radiation therapy of 31-60 days [compared to ≤30 days; EFS: HR=2.1, p=0.04], and treatment 2009 – 2013 cohort[OS: HR=2.2, p=0.02; EFS: HR=2.0; p=0.03]. CONCLUSIONS: Outcomes for Medulloblastoma at INEN were low compared with HIC. Anaplastic sub-type, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009 - 2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.
MODL-04. Drug screening in Disorders with Abnormal DNA Damage Response/Repair (DADDR) andin vivo validation
Authors: Kolodziejczak Anna , Selt Florian , Peterziel Heike , Jamaladdin Nora , Mack Norman , Maass Kendra , Kool Marcel , Herold-Mende Christel , El Damaty Ahmed , Oehme Ina , Jones David T W , Witt Olaf , Pajtler Kristian W , Kratz Christian , Pfister Stefan M , Milde Till 
Published: June 2022

Abstract
INTRODUCTION: Disorders with Abnormal DNA Damage Response/Repair (DADDRs) are inherited conditions caused by constitutional mutations of DNA damage response and repair genes and are characterized by an increased cancer risk. Furthermore, affected individuals also show an elevated risk of secondary neoplasms as well as excessive toxicity, poor therapy response and increased mortality when treated with standard radiation and chemotherapy regimens. The main aim of this project is to screen for potential novel chemotherapeutic approaches for these cancer entities, and to employ faithful PDX models for in vivo validation. METHODS: In vitro drug screening was performed using a custom library composed of 345 compounds targeting 61 different proteins. For two specific DADDRs, Li-Fraumeni syndrome (LFS) and Constitutional Mismatch Repair Deficiency (CMMRD), two cancerous (glioblastoma and medulloblastoma) and one non-cancerous cell lines were selected to model each of these conditions. Performance of each drug was assessed based on its efficacy (sensitivity score) and genotoxicity (micronucleus assay). For DADDR PDX model establishment tumor material from DADDR patients is currently being injected orthotopically (brain tumors) or subcutaneously (non-brain tumors) into NSG mice. Following engraftment and expansion, the PDX models will be characterized molecularly and compared with original patient material. RESULTS AND OUTLOOK: In vitro screening revealed n=26 drugs that fulfilled the following criteria: a) favorable toxicity in cancerous cell lines compared to non-cancerous cell lines, b) little to no genotoxic effect in non-cancerous cell lines. These characteristics qualify them as potentially suitable candidates for novel therapeutic approaches specifically for DADDR patients. The hits included inhibitors of ATM/ATR, CHK1/CHK2, DHFR, mTOR and PI3K, as well as microtubule-associated compounds. Combination testing and further validation of these hits using disease-specific in vitro and in vivo PDX models is ongoing.
MODL-21. Multi-omics investigation of medulloblastoma resistant models reveals functional association between intracellular regulatory networks and drug susceptibility
Authors: Mariotto Elena , Rampazzo Elena , Bortolozzi Roberta , Rruga Fatlum , Manfreda Lorenzo , Marchioro Chiara , Bresolin Silvia , Viola Giampietro , Persano Luca 
Published: June 2022

Abstract
Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Despite high-dose radio/chemotherapy treatment, 15-30% of patients still display a high risk of tumor recurrence. In this context, the characterization of innovative cellular models resembling therapy-induced drug resistance represents an unprecedented opportunity for selecting relevant therapies for chemotherapy-refractory patients. In order to unveil the molecular mechanisms sustaining chemotherapy resistance in MB, we setup in vitro models of MB drug resistance by exposing Patient-Derived MB (PD-MB) cells to a combination of the commonly used chemotherapeutics for pediatric MB treatment. Integration of multi-omics data, including transcriptional, proteomic and kinase activation profiling, disclosed that drug resistant PD-MB cells are characterized by a significant deregulation of several cancer-related pathways converging to metabolism of xenobiotics, adaptation of the biochemical processes sustaining energetic metabolic demand, cell proliferation and survival, protein homeostasis, RNA processing and modification, and immune response. Moreover, this intriguing regulatory network was functionally associated to the response of drug-resistant MB cells to a large library of compounds through a semi-automated High-Throughput drug Screening (HTS) workflow, suggesting the antimetabolite class of drugs as relevant therapeutics displaying high selectivity and efficacy against resistant MB models, together with a significant synergistic action when combined with standard chemotherapeutic agents. Collectively, our results suggest that drug-resistant MB cells are subjected to a peculiar adaptation of multiple intracellular processes during adaptation to chemotherapy, which protects them from the toxic environment but, at the same time, provides targetable vulnerabilities for therapeutic purposes.