bluuebunny/crossref_metadata_2025_split huggingface dataset:
LMIC-11. OUTCOMES OF INFANTS WITH CNS TUMORS: REPORT OF 85 CASES FROM 6 MEXICAN HOSPITALS
Authors: Benito-Reséndiz Alma Edith , del Campo Regina Navarro-Martín , Pantoja-Guillén Francisco , Escamilla-Asiain Gabriela , Ángeles-Romero Atzin , García-Robles Beatriz , Ruvalcaba-Sanchez Rafael , Nájera-Castillo Melisa , Tejocote-Romero Isidoro , Arce-Cabrera Daniela , Echevarria-Valenzuela Elsa , Ortiz-Azpilcueta Mariana , González Farina Arreguín , Sandoval-de Jesús San Juanita , García-Ramos Jeannie , Zapata-Sosa Imelda , Moreira Daniel 
Published: June 2024

Abstract

INTRODUCTION
Reports on central nervous system (CNS) tumors in infants from low- and middle-income countries are scarce. This is a high-risk population, we sought to analyze their outcomes in Mexico.

METHODS
Patients &lt;36 months diagnosed CNS tumors between January 2014 to December 2023 from 6 hospitals in Mexico were included. Demographic, treatment, and outcomes were collected.

RESULTS
In total, 85 patients with a median age of 21 months were included. Of these, 51 (60%) were male. Diagnoses included low-grade glioma (LGG) in 26 (33%), medulloblastoma (MB) in 19 (22%), other embryonal tumors in 12 (14%), ependymoma (EPN) in 11 (13%), high-grade glioma (HGG) in 6 (7%), and other tumors in 11 (13%). Regarding surgery, a near or gross total resection was achieved in 22 patients (26%). For LGG it was 23%, while it was 37% for for MB, 36% for for EPN, and 17% for HGG. Ten patients (12%) died from postoperative complications. Overall, 12 (14%) patients, including 4 patients with MB, had metastasis at diagnosis. In total, 19 (22%) patients received radiotherapy, including 10 patients who received CSI (average age 35 months) and 9 who received focal radiotherapy, including 6 with EPN, 2 with LGG, and 1 with ATRT. Of patients with MB, 18 (95%) received chemotherapy, including 1 with autologous stem cell transplant and 3 with intraventricular chemotherapy. The 5-year event-free survival was 38±11%, while the 5-year overall survival (OS) was 52±10%. The 5-year OS were: 84±10% for LGG, 43±21% for MB, 55±23% for EPN, 9±25% for other embryonal tumors, and 17±35% for HGG.

CONCLUSIONS
These data show low survival rates, associated with very poor surgical outcomes. A fraction of patients received CSI radiotherapy, showing deviation from international standards. Further analyses are needed to identify factors that lead to better prognosis.
LMIC-21. SERIES OF 9 CASES OF SPINAL CORD COMPRESSION IN CHILDREN: A SINGLE EXPERIENCE FROM THE PEDIATRIC NEURO-ONCOLOGY GROUP, IN A MIDDLE INCOME COUNTRIES
Authors: Morikawa Karina Amélia , Komatsu Mariana Massue , Sanders Felipe Hada , Lucato Leandro Tavares , Baraldi Helena , Casal Yuri Reis , Barreto Juliana Silveira , Cristófani Lilian , Filho Vicente Odone , Weltman Eduardo , de Azambuja Alessandra Prandini 
Published: June 2024

Abstract

BACKGROUND
Spinal cord compression secondary to pediatric neoplasms is a rare but serious event that can result in irreversible neurological sequelae, with paralysis, sensory losses and sphincter dysfunction. This retrospective study aims to describe the main causes, treatments and outcomes of a series of cases of spinal cord compression in patients admitted to the Childhood Cancer Treatment Institute- ITACI, University of São Paulo, Brazil.

METHODS
Based on data collected from the pediatric neuro oncology group, we analyzed nine cases of spinal cord compression in patients under 18 years, admitted from 2020 to 2023.

RESULTS
In our case series, 7 of the 9 children were female, with an average age of 104 months, the youngest being 3 months. Of the cases described, 77.7% had extradural spinal cord compression. Ewing’s sarcoma was the main neoplasm associated with extradural compression, representing 44.4%. Neuroblastoma, giant cell tumor and B acute lymphoblastic leukemia accounted for 11.1% of cases each. Cases of intradural compression were represented by low-grade glioma with cervical compression and germ cell tumor from with thoracolumbar lesion. Spinal cord compression was the first manifestation of malignancy in 8 of the 9 patients, who presented loss of motricity and sensitivity. All patients were treated with corticosteroid, therapy due to its benefits in reducing vasogenic edema caused by spinal cord compression. Additionally, 8 patients underwent surgical spinal decompression. A patient with Ewing sarcoma received cytoreductive chemotherapy and achieved complete motor recovery.

CONCLUSIONS
Spinal cord compression is associated with serious neurological sequelae when not treated appropriately. However, neurological recovery is possible with early diagnosis and adequate decompression treatment. We increased the importance of specialized services with a pediatric neuro-oncology group, in which several professionals work together to provide individualized care, even in developing countries, as demonstrated by the patients treated at our institution.
LMIC-24. ASSESSING THE TREATMENT OUTCOMES OF PEDIATRIC PATIENTS WITH MEDULLOBLASTOMA UNDER A U.S.-MEXICO CROSS-BORDER NEURO-ONCOLOGY PROGRAM
Authors: Crawford John R , Tenorio Alexander , Brandel Michael , Adams John , Kumar Nikhil , Gomez Rebeca Rivera , Gonda David , Levy Michael L , Aristizabal Paula 
Published: June 2024

Abstract

BACKGROUND
Treating pediatric brain tumors in low-income countries is associated with worse outcomes, likely due to requiring a highly trained interdisciplinary team with ample resources. The Cross-Border Neuro-Oncology Program (CBNP) between Rady Children’s Hospital, San Diego (RCHSD), and Hospital General, Tijuana (HGT), was established to provide comprehensive care for children with brain tumors diagnosed at HGT. Given the most common malignant pediatric brain tumor is medulloblastoma, assessing treatment outcomes for this tumor is essential to establish this program’s validity.

METHODS
Pediatric patients with medulloblastoma were recruited from 2012-2021 as part of CBNP and risk-stratified into one of two treatment protocols (low - (K) versus high-risk (Y)). Patients underwent surgical resection and chemotherapy, which included cisplatin, etoposide, vincristine, and cyclophosphamide; patients with higher risk additionally received radiation therapy and higher-dose chemotherapy. Clinicopathologic profiles, extent of resection, methylation status and protocol type were analyzed and compared to known prognostic values for pediatric medulloblastoma.

RESULTS
Seventeen patients with medulloblastoma (age at diagnosis=6.8±5.0 years) were treated as part of CBNP during the study period. Patients were admitted to HGT, underwent resection at RCHSD, and returned to HGT for collaborative management. The mean symptom duration preceding diagnosis was 72.1±99.2 days. Gross total resection was achieved in 53% of cases and 5-year overall survival was 53% (9/17). Eight (47%) patients had residual post-treatment cerebellar signs. Survival data correlated with protocol type and methylation status will be presented.

CONCLUSION
Our cohort demonstrated a 5-year overall survival of 53%, moderately lower than the reported average 5-year overall survival of ~70% for pediatric medulloblastoma, with the majority of our cohort comprising of higher risk subtype and pathology. This indicates that this twinning model is a valid archetype for treating pediatric patients with brain tumors in low-income countries.
LMIC-25. EXPANDING THE PEDIATRIC NEURO-ONCOLOGY TELECONFERENCE EXPERIENCES, A LUXURY, OR A NECESSITY?
Authors: Badarin Essra’ Al , Chamdine Omar , El-Ayadi Moatasem , Al-Battashi Abeer , Nuaimi Mohammed Al , Alshamsi Emam , Hessissen Laila , Al-Tarrah Hiba , Maher Eslam , farah Roula , Maaz Ata Ur Rehman , Saed Waleed , Haziemeh Ruba , Mustafa Maher Khader , Salami Khadra , Hawkins Cynthia , Abdelbaki Mohamed , Bartels Ute , tabori Uri , Bouffet Eric , Amayiri Nisreen 
Published: June 2024

Abstract

INTRODUCTION
Videoteleconference in neurooncology is feasible and sustainable. The well-established 20 years’ Sickkids/KHCC teleconferencing is an example. Since 2018, several regional centers joined these meetings to discuss their patients’ management plans. We aimed to evaluate the impact of this experience.

METHODS
We retrospectively reviewed the 56 meetings’ minutes (9/2018-12/2023) and compared the pre-conference suggested plans with the post-conference recommendations. We recorded if the recommendations were implemented and the impact perceived.

RESULTS
In total, 251 patients were discussed: KHCC (137) and non-KHCC (114). Four of the regional participating oncologists had dedicated pediatric neuro-oncology training. Patients were selected for discussion due to challenges in their management (i.e. with relapsed tumors, rare diagnoses, unexpected tumor behavior). Main diagnoses were: Low-grade-glioma (28%), High-grade-glioma (21%), and Medulloblastoma (17%). Of the 227 patients where the local team suggested a care plan, the teleconference recommendations concurred with the proposed plan in 50% of the cases, agreed on but provided an alternative plan option in 18% and disagreed on in 32% of the cases. The difference in recommendations mostly affected the proposed treatment modality (15%). In 64% of the discordant plans and 50% of the alternative plans, the treating team applied the recommendations. Challenges to apply the recommendations were mainly linked to patients’ factors (53%, plan refusal, traveling abroad, clinical deterioration), local multidisciplinary team consensus on a different plan (29%) or logistic difficulties (18%, e.g. drug access).

CONCLUSIONS
Improvement in patients’ care was likely achieved with the continuous effort of the local teams to implement the recommendations. Participating oncologists valued the shared educational experience learned from each other’s case discussions, especially those related to molecular-testing and implications on treatment. Joining such regional teleconferences is of particular importance to small-volume centers or those lacking a pediatric neurooncologist. Regional and international collaborations are a necessity when it comes to improving the care of children with CNS tumors.
MODL-02. ESTABLISHING THE TIME-DEPENDENCE OF CDK4/6 INHIBITOR EFFICACY IN PEDIATRIC BRAIN TUMORS AND FEASIBILITY OF METRONOMIC INTRATHECAL DELIVERY IN A PRECLINICAL MODEL
Authors: Martin Brice , Guadix Sergio , Sathian Rekha , Laramee Madeline , Pandey Abhinav , Ray Ishani , Chen-Kiang Selina , Wang Amy , Davuluri Ramana , Dahmane Nadia , Thomas Craig , Souweidane Mark 
Published: June 2024

Abstract
This comprehensive study delves into the intricate dynamics of CDK4/6 inhibitors (abemaciclib, ribociclib, palbociclib) efficacy in the context of pediatric brain tumors, with a specific focus on establishing the temporal dependencies of their effectiveness. Beyond elucidating the time-dependent aspects, the research also explores into the feasibility and safety considerations associated with a metronomic intrathecal delivery with Palbociclib. This involves a thorough examination of pharmacokinetics and an analysis of liver and renal function through a panel assessment in vivo. By methodically exploring the optimal dosing within the brain after administration of Palbociclib via a systemic or intrathecal administration; the study aims to provide nuanced insights into enhancing therapeutic outcomes for pediatric brain tumors. Ultimately, we also provide a mechanistic understanding of the inhibition of CDK4/6 over time using RNAseq analysis; and an assessment of the efficacy of the proposed metronomic intrathecal delivery strategy in a preclinical mouse model of leptomeningeal ATRT. This multifaceted study not only expands our understanding of the temporal dynamics of CDK4/6 inhibitors but also lays the foundation for informed decision-making regarding the potential of this innovative therapeutic delivery method in the realm of pediatric brain tumor treatment.
MODL-11. LOW-GRADE GLIOMA 3D PATIENT-DERIVED ORGANOID PLATFORM AS TRANSFORMATIVE TOOL FOR TUMOR BIOLOGY AND TRANSLATIONAL RESEARCH
Authors: Beale David R , Alonso Alana Martinez , Baubet Valerie P , Santi-Vicini Mariarita , Viaene Angela , Madsen Peter , Koptyra Mateusz P , Storm Phillip B , Resnick Adam C 
Published: June 2024

Abstract
Unlike many high-grade tumors, low-grade glioma (LGG) has faced challenges in advancing scientific and clinical breakthroughs, affected by the limited capacity to develop representative preclinical tumor models. Major barriers to establishing traditional LGG cell culture systems have been cellular senescence and the need to introduce additional genetic modifications to obtain cultured growth. Such LGG models, while extremely valuable, require extensive periods for development and result in clonally selected lines which may not present the complexity of LGG tumor biology. To mitigate such challenges in LGG model development and address the need for three-dimensional tissue cultures, we have successfully generated organoids from fresh tissue specimens obtained from surgical resection. We have demonstrated success of this method on various pediatric brain tumor histologies and have expanded these approaches successfully to LGG. Through such efforts, we have developed 14 LGG tumors’ organoid models as well as other low-grade tumor’s models such as craniopharyngioma, schwannoma, meningioma, optic glioma, and oligodendroglioma. The tissue was processed immediately post-extraction and cultured in media solution on rotating platform. Organoid growth was observed within 1-3 weeks of initiation and tested for growth for up to 3 months. Phenotypic analysis revealed organoid cell composition representing clinical histology. The immune component was preserved in organoids for up to 40 days. MAPK pathway activity, a hallmark marker for KIAA-BRAF fusion positive pilocytic astrocytoma was preserved for up to 4 weeks. Our successful deployment of three-dimensional patient-tissue derived organoids provides for an efficient, simple workflow for the generation of unique and transformative preclinical models for the LGG field. Supported by the Children’s Brain Tumor network’s open science model, 3D organoids will provide investigations with broader resources for LGG tumor biology preclinical testing and support translational studies on behalf of the development of novel clinical trials.
MODL-13. ORGANOTYPIC BRAIN SLICE CULTURE PLATFORM AS A MODEL OF PEDIATRIC LOW GRADE GLIOMAS
Authors: Mann Breanna , Artz Nichole , Adefolaju Adebimpe , Dasari Rajaneekar , Bell Noah , Buckley Andrew , Kram David , Hingtgen Shawn , Satterlee Andrew 
Published: June 2024

Abstract

BACKGROUND
Pediatric low grade glioma (pLGG), the most common subgroup of central nervous system tumors in children, suffers from a paucity of models that support pLGG biological discovery, preclinical target identification, and drug screening studies.

METHODS
We propose the use of an organotypic brain slice culture (OBSC) platform as a novel model in which we are able to reliably support fresh, zero-passage pLGG patient tumor tissue for preclinical testing. We performed individualized drug screening with the frequently used up-front agents: carboplatin, vincristine, trametinib, and dabrafenib.

RESULTS
We have collected and established on OBSCs 100% (3/3) pLGGs since 2023. With these three patient samples, we have applied our quantitative drug screening algorithm, which combines tumor killing efficacy with healthy tissue toxicity, and yielded resultant drug sensitivity scores (DSS) to quantify patient-specific treatment efficacies.

CONCLUSIONS
Overall, these early results suggest that the OBSC platform may serve as a novel and reliable model for pLGG, filling a critical void in representative models for this common and often highly morbid pediatric tumor.
RADT-05. MATURE OUTCOMES OF A PHASE II PROSPECTIVE STUDY OF PROTON RADIOTHERAPY FOR LOCALIZED BRAIN TUMORS
Authors: Kang Soo , Anderson Emily , Bajaj Benjamin , Allison Keith , Gallotto Sara , Lawell Miranda , Perry Alisa , Yock Torunn 
Published: June 2024

Abstract

BACKGROUND
Proton radiotherapy (PRT) is a highly targeted form of radiation that spares more normal brain tissue compared to modern photon radiotherapy. Therefore, we expect the late effect profile in children treated with PRT with curable brain tumors should be improved.

METHODS
Between 2010-2022, 100 patients were enrolled, treated with PRT, and then followed for disease control, hearing, neurocognitive and endocrine outcomes. Late effects of the tumor and treatment delivered were graded using CTCAE v4.0.

RESULTS
Median age at PRT was 8.0 years (1.1-20.8) and median follow up was 8.7 years (0.3-12.7). Tumor types included 40 (40%) ependymomas, 19 (19%) low grade gliomas (LGG), 21 (21%) craniopharyngiomas, and 20 (20%) other histologies. 26% of patients were treated with chemotherapy in addition to PRT. The location of PRT was 38 (38%) infratentorial, 56 (56%) supratentorial, and 6 (6%) both. The median radiation dose was 52.2 GyRBE (48.6-59.4). 8-year event-free survival (EFS) and overall survival (OS) was 71.7% and 86.2% for all patients. 8-year EFS and OS was 59.9% and 82.4% for ependymomas, 78.2% and 94.7% for LGG, 80.0% and 87.7% for craniopharyngiomas and 79.1% and 84.7% for all other tumor types. 19% of patients had new grade 3+ toxicities that were at least possibly related to radiotherapy. Baseline full-scale intelligence quotient (FSIQ) was 98.0 and follow-up FSIQ was 101.8 (p=0.14). 43% of patients had new endocrine deficiencies after radiation. 8 patients suffered new high-grade hearing loss after PRT. Dosimetry on critical brain structures was collected and correlated with late effects. More details will be presented at the conference.

CONCLUSION
PRT remains an effective treatment for children with curable brain tumors. While late effects of the tumor and treatment are still present, the overall burden of late effects is lower than other reports.
STEM-05. CREATING PATIENT-DERIVED TUMOROIDS TO INVESTIGATE RADIORESISTANCE IN PEDIATRIC BRAIN TUMORS
Authors: Deschuyter Marlène , Pelletier Rémi , Salmanli Chinar , Wolf Thibaut , Lhermitte Benoit , Reita Damien , Guerin Eric , Foppolo Sophie , Klymchenko Andrey , Dontenwill Monique , Martin Sophie , Entz-Werle Natacha 
Published: June 2024

Abstract

BACKGROUND
Brain cancers are the most frequently diagnosed tumor types in pediatric and young adult populations. Unfortunately, they often carry a poor prognosis and face common challenges such as treatment resistances due to intra- and intertumoral heterogeneity. To fully understand the intrinsic and extrinsic mechanisms which might hinder proper care, there is an emerging need to develop precise models of brain tumors to understand resistances and to predict therapeutic responses. While tumor-derived primary cell lines are relatively easy to produce, fully replicate the complexity of tumors as they grow without interactions with and from the microenvironment. Therefore, the advent of organoid cultures represents a significant advancement in modelling development. Derived from this technology, tumoroids offer a promising solution for modeling 3D tumors and their complex microenvironment.

METHODS
We develop tumoroids from fresh biopsies and patient-derived tumor xenografts. These models were rigorously validated against to initial tumor using confocal microscopy, methylome analyses, metabolomics and single-cell RNAseq. To assess the intrinsic hypoxic environment and its spatial heterogeneity, characteristic of aggressive cancers, we employed fluorescent oxygen-sensitive dye loaded polymeric nanorods.

RESULTS
We successfully generated tumoroids using PDX of ependymomas (BT39) and it paired relapse (BT42), two H3.3 mutated high-grade gliomas (BT35 and BT69), one ganglioglioma (BT63) and directly from fresh biopsies of DIPG sample (BT140). Several passages were obtained after primary derivation, and cryopreservation demonstrating the stability of the models over time. Tumoroids displayed similar protein and omics markers as their parental tumors and harbored specific stem cell and neural progenitor markers. The methylation patterns were entirely preserved comparing 3D models and their parental tumors, and other multiomics and metabolic approaches confirmed the accurate reconstitution of tumor complexity. The study of oxygen-sensitive nanorods highlighted the heterogeneous oxygen gradient within tumoroids.

CONCLUSIONS
All these initial characterized tumoroids helped us to develop radioresistant paired models.
STEM-07. CONSERVATION AND FAITHFUL REPRESENTATION OF CIRCULAR EXTRACHROMOSOMAL DNA IN ORTHOTOPIC PATIENT-DERIVED MEDULLOBLASTOMA XENOGRAFTS
Authors: Kenkre Rishaan , Chapman Owen , Luebeck Jens , Bafna Vineet , Wechsler-Reya Robert J , Mesirov Jill , Chavez Lukas 
Published: June 2024

Abstract

BACKGROUND
Extrachromosomal DNA (ecDNA) drives tumor heterogeneity and correlates with poor survival across various cancer types. Patient-derived xenograft (PDX) models facilitate preclinical drug testing in vivo, enabling tumor growth analysis and molecular tumor profiling. These models, combined with single-cell profiling, offer insights into intratumoral heterogeneity under therapeutic pressure and the emergence of drug resistance. We investigate the abundance and conservation of ecDNA in PDX models to assess the faithful representation of ecDNA compared to their corresponding primary tumors.

METHODS
Whole-genome sequencing (WGS) was applied to 27 medulloblastoma (MB) PDX models and their tumors of origin using Amplicon Architect. ecDNA frequency in these models was also compared to that in the MB patient population. Optical genome mapping enabled accurate and reliable ecDNA sequence reconstructions. Multiome single-cell RNA and ATAC-sequencing of a PDX tumor enabled analysis of ecDNA conservation and intratumoral heterogeneity compared to similar data previously obtained from the primary tumor.

RESULTS
ecDNA is largely conserved in PDX models, emphasizing their relevance as faithful models of the primary tumors. MB PDX models exhibit significant higher ecDNA frequency (16 out of 27 tumors) as compared to their frequency in the overall patient population (~18%), suggesting ecDNA as a driver for successful establishment of MB PDX models. Single-cell analysis revealed that ecDNA is omnipresent in almost all PDX tumor cells, contrasting with only ~9% of tumor cells in the primary tumor.

CONCLUSIONS
ecDNA analysis in medulloblastoma primary tumors and in PDX models revealed that ecDNA is preserved in PDX models. These findings emphasize the relevance of PDX models in preclinical in vivo studies aimed at analyzing the role of ecDNA under therapeutic pressure and for analyzing clonal selection along with molecular evolution of ecDNA during the development of therapeutic resistance.
Science and the nation-state: What China’s experience reveals about the role of policy in science
Authors: Wagner Caroline S 
Published: June 2024

Abstract
China’s rapid rise and spectacular growth in science capacity reopens a discussion about the relationship between science and the nation-state. Literature suggests that science thrives within a democratic system and that scientific activities tend to have a liberalizing effect on governments. Neither of these phenomena appears evident in China’s case. Three policies, present in the earliest days of the growth of modern science, ones in common with other nations, factor into China’s science policy: (1) policies enabling protection of intellectual property, (2) encouraging mobility and skills development, and (3) government procurement of science and technology, especially through military purchases. Using Graham’s interactionist model, I suggest that policies instituted by the state-created conditions for emergence of modern science.