bluuebunny/crossref_metadata_2025_split huggingface dataset:
PALC-01. CARING FOR DYING CHILDREN: EXPERIENCES OF FAMILY CAREGIVERS OF CHILDREN RECEIVING PEDIATRIC PALLIATIVE TREATMENT
Authors: Tanrıverdi Müberra , Yılmaz Güleser Güney 
Published: June 2024

Abstract

INTRODUCTION
Caring for children living with life-threatening and life-limiting illnesses can be challenging for families. Parents’ roles as primary caregivers can be complex, with extensive responsibilities.

METHOD
A mixed-design study was conducted with the caregivers of 26 children receiving treatment in palliative care. In the qualitative part of the research, a semi-structured interview was conducted and the question “What does caring for a child with advanced stage cancer mean to you? What are your concerns and concerns?” were asked. In the quantitative part, the caregiving burden scale, Beck Anxiety Questionnaire and WHOQOL-BREF quality of life scale were used. The relationship between quality and other factors was examined with Pearson correlation analysis. Phenomenological content analysis was performed for qualitative data.

RESULTS
As a result of the analysis of the data, two main themes were identified. The main themes from family caregivers’ experiences included (1) fear and anxiety about losing their child, and (2) disconnection from other children and families. A statistically significant negative relationship was detected between caregivers’ caregiving burden, anxiety levels, quality of life and sub-parameters (General Health, Physical Health, Mental Health, Social Health, Environmental Health) (p&lt;0.001).

CONCLUSION
Caring for a dying child with cancer can pose psychological challenges as well as medical and physical ones. Families’ resilience, family dynamics and quality of life can be significantly affected. Treatment processes in palliative and oncological care are multifactorial and should include families.
PATH-02. THE IMPACT OF EVOLVING DIAGNOSTIC METHODOLOGY ON THE CLASSIFICATION AND OUTCOME OF CENTRAL NERVOUS SYSTEM TUMOURS IN CHILDHOOD: A RETROSPECTIVE COHORT STUDY
Authors: Kirby Maria L , Hansford Jordan R 
Published: June 2024

Abstract

BACKGROUND
Central nervous system tumours are the second most common childhood tumours and the largest cause of childhood cancer death in Australia. Tumours arise from many cell types within the developing and mature CNS, leading to a wide spectrum of clinical behaviour despite overlapping histological appearances. Emerging molecular testing methods allow more precise determination of cell lineage as well as genetic and epigenetic changes driving tumour development. Particularly since 2016, molecular findings have been incorporated into international classification schema, potentially impacting the frequency of individual diagnoses and their observed prognosis.

METHODS
We performed a retrospective cohort study including patients with newly diagnosed CNS tumours at Royal Children’s Hospital, Melbourne between 2011 and 2020 (total 473). The first and last 100 eligible patients in the data set were reviewed for diagnosis, survival and recorded use of molecular testing. Reviewed patients were assigned to one of two cohorts, Cohort 1 2011-2013 (pre-2016 WHO revision) or Cohort 2 2018-2020 (post-2016 WHO revision).

RESULTS
The frequency of diagnoses on biopsy rather than imaging alone was stable (81% Cohort 1 vs 83% Cohort 2). Molecular testing utilization increased markedly over time (10 molecular investigations in Cohort 1 vs 348 in Cohort 2). The incidence of astrocytic and oligodendroglial diagnoses was stable. The incidence of embryonal and neuronal/ mixed glial neuronal diagnoses increased in Cohort 2, and the incidence of ependymal diagnoses decreased (p=0.0122). There were no event free or overall survival differences between the whole of Cohorts 1 and 2, with numbers of individual diagnoses too small for meaningful comparisons over time.

CONCLUSIONS
Access to molecular testing has impacted on the pattern of reported diagnoses of central nervous system tumours in children. Although outcomes have not changed, it is hoped that over time, improved molecular understanding will lead to more effective therapy selection.
PATH-04. OPTIMIZING CELL-FREE DNA ASSAYS FOR LOW INPUT LIQUID BIOPSY SAMPLES FROM PEDIATRIC BRAIN TUMOR PATIENTS
Authors: Fischer Tom T , Maaß Kendra K , Puranachot Pitithat , Mieskolainen Markus , Sill Martin , Finster Agnes M E , Schad Paulina S , 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 2024

Abstract

BACKGROUND
Genetic and epigenetic profiling have transformed biological understanding, diagnostics, and therapeutic approaches for pediatric central nervous system (CNS) tumors. Obtaining tumor tissue may be associated with neurosurgical risk, may not be feasible in some cases, and is not routinely performed during follow-up or at relapse. Liquid biopsies (LBs) have emerged as a minimally invasive, serially collectable source of tumor-derived DNA. Here, we collected cerebrospinal fluid (CSF) and serum LBs from a large, unselected, cross-entity pediatric CNS tumor cohort (n=55 patients) for method optimization.

METHODS
Cell-free DNA (cfDNA) isolated from CSF and serum samples was analyzed 1) by low-coverage whole genome sequencing for copy number variation (CNV)-based tumor detection and 2) by enzymatic conversion (EC)-based DNA methylation profiling using the EPIC DNA methylation array and the Heidelberg Brain Tumor Classifier. All library protocols were optimized for LB samples with low cfDNA amounts in the picogram range. Matched tumor samples were used as reference.

RESULTS
Our lcWGS-based cfDNA profiling protocol had a high technical success rate across the whole cohort (&gt;95%), despite very low cfDNA amounts for most CSF samples. The majority of CSF LBs captured tumor-derived CNVs and displayed a high fraction of tumor-derived cfDNA (&gt;5%, range 0-78%). For serum LBs, only few samples showed detectable CNVs. Proof-of-concept methylation analyses leveraging a new EC-based workflow allowed molecular classification using CSF, particularly for embryonal brain tumors (11/15 samples). Clinical workup of selected cases illustrates the potential of LBs to aid as diagnostic tool, monitor disease, and characterize tumor evolution.

CONCLUSIONS
Tackling a major roadblock of clinical translation of LBs, this study delineates new methods tailored to low input cfDNA samples. Results highlight the clinical utility of LBs for the management of brain tumor patients, providing a strong rationale for prospective validation within pediatric neuro-oncology trials.
PATH-07. SPINAL OCCURRENCE OF INTRACRANIAL MESENCHYMAL TUMOR WITH FUS::CREM FUSION
Authors: Edminster Sarah , Tran Hung N , Ji Jianling , Abdullaev Zied , Aldape Kenneth , Cotter Jennifer 
Published: June 2024

Abstract

BACKGROUND
Intracranial Mesenchymal Tumor (IMT), with FET::CREB fusion is a rare and recently characterized tumor. Previously, they were classified as intracranial myxoid mesenchymal tumor and angiomatoid fibrous histiocytoma-like neoplasms. Presence of FET::CREB gene fusion defines the entity, however the incidence and prognosis are not well understood.

CASE PRESENTATION
Our 6-year-old female patient presented with 6 weeks of neck pain. MRI revealed a posterior intradural extramedullary cervical spine mass (2.4 x 1.4 x 1 cm). She subsequently underwent complete tumor resection. H&E showed a round cell neoplasm, in a lobulated architecture with thick interstitial collagen. Mitotic activity was rare. Immunohistochemistry for CD99 and desmin were positive, with focal synaptophysin expression. The tumor lacked specific immunohistochemical features to enable further classification. OncoKids next generation sequencing revealed an in-frame FUS::CREM fusion. DNA methylation profiling matched to an IMT with FET::CREB fusion. Post-operatively, she had pain resolution and is without recurrence 3 months later.

DISCUSSION
IMTs have gene fusions of the FET RNA-binding protein family (EWSR1 or FUS) with a member of the CREB family of transcription factors (CREB1, ATF1, or CREM). This fusion creates a chimeric protein with altered function. EWSR1 is the most common fusion partner. IMTs have a broad morphological spectrum that overlaps with other entities making molecular studies essential for the diagnosis. While most IMT are supratentorial, few spinal cord examples have been reported. Optimal treatment strategy remains undefined, but adjuvant radiation therapy may be considered, especially for incompletely resected tumors.

CONCLUSION
FET::CREB fusion defines IMT, a tumor type that is typically intracranial. Spinal cord occurrence is possible, although less well-recognized. They have a broad morphological spectrum, immunohistochemical overlap with other entities, and molecular studies are required to make the diagnosis. Further studies to characterize their clinical behavior to guide future treatment are needed.
PATH-08. PRE-OPERATIVE TUMOUR CLASSIFICATION USING NANOPORE SEQUENCING OF CEREBROSPINAL FLUID
Authors: Stepien Natalia , Senfter Daniel , Freund Julia , Machreich Sarah , Bruckner Katharina , Mager Leah , Laemmerer Anna , Jaunecker Carola , Pirker Christine , Lötsch-Gojo Daniela , Mayr Lisa , Hedrich Cora , Lippolis Maria Aliotti , Schned Hannah , Köller Clara , Kiesel Barbara , Dorfer Christian , Azizi Amedeo A , Peyrl Andreas , Schmook Maria T , Euskirchen Philipp , Pagès-Gallego Marc , Vermeulen Carlo , Tops Bastiaan , Haberler Christine , Müllauer Leonhard , Madlener Sibylle , Gojo Johannes 
Published: June 2024

Abstract

BACKGROUND
The introduction of tumour classification by analysis of DNA methylation has changed the landscape of paediatric neuro-oncology. With the launch of Oxford Nanopore sequencing, generation of sequencing data is possible in real-time, including information on base-modifications. Diverse classification tools for tumour tissue have been developed recently. While this is an important step towards optimization of surgical treatment, pre-operative knowledge on tumour entity would further facilitate surgical planning. Therefore, we investigated the possibility of liquid biopsy for rapid pre-operative tumour classification.

METHODS
CSF samples from patients with pre-operative extra-ventricular drain (EVD) (n = 5) as well as samples obtained via Ommaya reservoirs in cases of suspected recurrence (n = 3) were analysed. Additionally, samples from non-tumour patients (epilepsy, inflammation) who had lumbar puncture were available as controls. Samples were sequenced on MinIon devices (Oxford Nanopore) and subsequently classified with previously published tumour tissue classification pipelines (NanoDx, crossNN, Sturgeon).

RESULTS
Even though CSF derived from EVD has been stored on room temperature for up to 72 hours before processing, cfDNA isolation was possible with the advantage of higher CSF input amounts. DNA fragments showed a distribution characteristic for cell-free DNA, with a maximum peak at 170bp. The amount of total input DNA ranged from 0.35ng to 12ng, with higher input amounts generating more sequencing data but not resulting in better classification. Classification by sturgeon and crossNN/nanoDx using CSF derived cfDNA was possible in exemplary cases, such as a medulloblastoma patient with a new inoperable lesion, where CSF analysis resulted in medulloblastoma Group 4 within the first hour of sequencing. In total, 38% of samples were correctly classified.

CONCLUSION
Liquid biopsy as a method to pre-operatively classify tumours and thereby enable risk-adjusted surgery is feasible. Ongoing efforts focus on optimisation of ctDNA based tumour classification by extension of the cohort.
PATH-10. ACCELERATING COMPREHENSIVE CNS TUMOR MOLECULAR DIAGNOSTICS WITH RAPID-CNS2 AND MNP-FLEX: A PROSPECTIVE MULTI-CENTER VALIDATION
Authors: Patel Areeba J , Göbel Kirsten , Hinz Felix , Dogan Helin , Schrimpf Daniel , Göller Pauline , Leske Henning , Halldórsson Skarphéðinn , Fox Graeme , Deacon Simon , Paine Simon , Smith Stuart , Jäger Natalie , Herold-Mende Christel , Wick Wolfgang , Pfister Stefan M , Vik-Mo Einar , von Deimling Andreas , Schlesner Matthias , Jones David T W , Loose Matthew , Sill Martin , Sahm Felix 
Published: June 2024

Abstract

BACKGROUND
The 2021 WHO classification update highlights the necessity of integrating molecular alterations for precise central nervous system (CNS) tumor diagnoses. However, current molecular reporting methods are hindered by significant initial investment, labor-intensive protocols, and lengthy turnaround times. Methylation-based classification has emerged as a pivotal diagnostic tool but is currently limited to array-based techniques. This necessitates exploration of novel technologies to streamline molecular analysis.

METHODS
We implemented Rapid-CNS2 - our adaptive sampling-based nanopore sequencing workflow- on 190 adult and pediatric samples at University Hospital Heidelberg and University of Nottingham. Intraoperative potential was assessed through real-time analysis followed by 24-hour sequencing for comprehensive genomic insights. Additionally, we developed MNP-Flex, a platform-agnostic version of the Heidelberg methylation classifier covering 184 CNS tumor classes. We evaluated MNP-flex on a global cohort of over 78,000 samples from methylation arrays, whole genome bisulfite sequencing, nanopore whole genome sequencing, methylation panels and Rapid-CNS2.

RESULTS
Rapid-CNS2 validation yielded accurate integrated diagnoses in all 190 samples. Within a crucial 30-minute timeframe, we reported accurate methylation families and arm-level copy number profiles followed by next-day reporting of fine-grained methylation classification, SNVs, focal CNVs, MGMT status, fusions and novel structural variants. Moreover, MNP-Flex achieved 92% accuracy over the validation dataset spanning over 78,000 samples from five different technologies.

CONCLUSIONS
The adoption of Rapid-CNS2 and MNP-Flex enables rapid intraoperative broad methylation classification and copy number alteration reporting within 30 minutes, with additional clinically relevant, fine-grained molecular insights available the following day. It offers clinicians rapid access to comprehensive molecular information critical for treatment decisions. Furthermore, MNP-Flex extends the utility of the Heidelberg methylation classifier to diverse sequencing-based data. By overcoming the limitations of currently available methods, our workflow represents a paradigm shift in the field, promising improved management of CNS tumor patients. Rapid-CNS2 can be executed with a single command, while MNP-Flex is publicly available as a web service, enhancing accessibility and usability for clinical applications.
PATH-12. ROBUST CELL-FREE DNA METHYLATION-BASED CLASSIFICATION OF PEDIATRIC BRAIN TUMOR LIQUID BIOPSIES
Authors: Smith Kyle S , Fischer Tom T , Lin Hong , Senfter Daniel , Wedig Tatjana , Schwarz Nathalie , Stepien Natalia , Madlener Sibylle , Haberler Christine , Hulleman Esther , Atkinson Natasha , Dhanda Sandeep K , Pfister Stefan , Upadhyaya Santhosh , Gajjar Amar , Robinson Giles W , Haapasalo Joonas , Haapasalo Hannu , Nordfors Kristiina , Gojo Johannes , Maass Kendra K , Pajtler Kristian W , Northcott Paul A 
Published: June 2024

Abstract

BACKGROUND
DNA methylation-based classification has been transformative in the molecular diagnostics of pediatric brain tumors, while additionally providing foundational insights into disease biology. Current diagnostic pipelines integrate histopathology and molecular tools in accordance with the WHO classification of CNS tumors which rely on the availability of tissue specimens. However, sometimes tumors are not amenable to neurosurgical resection due to their high-risk locations. Likewise, tissue collection is not routinely performed longitudinally. Liquid biopsies (LBs) have emerged as a minimally invasive, serially collectable source of tumor-derived material that have shown promise in detecting minimal residual disease (MRD) in pediatric neuro-oncology. Still, success rates of LB profiling have varied between studies, warranting the deployment of more reliable and reproducible assays.

METHODS
In the current study, we implemented a novel cell-free DNA (cfDNA) methylation sequencing (EM-seq) workflow in a large cohort of cerebrospinal fluid (CSF) samples (n&gt;200 patients) representing most pediatric brain tumor entities. Optimization of EM-seq for CSF specimens enabled the generation of genome-wide cfDNA methylation profiles from minimal starting material. Utilizing well-established CNS tumor DNA methylation datasets as references, we trained a deep neural network specializing in the classification of low tumor burden and sparse methylation profiles. Implementation of a novel tumor enrichment algorithm, coupled with DNA methylation imputation and subsequent deconvolution, facilitated detection and classification of low tumor burden samples, including those with balanced genomes that would have been overlooked using previous generation assays.

RESULTS
Our LB-based classifier allowed for highly accurate tumor detection and entity prediction (AUC=0.9) across the cohort. Case examples highlight the potential of this approach in establishing tumor classifications in inoperable cases and in performing serial disease monitoring.

CONCLUSIONS
Collectively, this study provides a blueprint for developing a CSF-based tumor classifier from cfDNA methylation profiles, and the motivation for prospective validation in future clinical trials.
LMIC-01. SURVIVAL AND PROGNOSTIC FACTORS IN CHILDHOOD MEDULLOBLASTOMA SINGLE TERTIARY CENTER EXPERIENCE FROM KING FAHAD MEDICAL CITY KFMC SAUDI ARABIA
Authors: Mobarak Nahla Aly , Balbaid Ali Abdullah O , Alotabi Fahad , Banyan Ayman Al , Alluhaybi Abdulelah A , Ahmad Maqsood , AlYahya Amal S , AlYamany Basma Mahmoud , Shakweer Wafa Al , Abedalthagafi Malak , Al-Dandan Sadeq , Aljabarat Wael , AlNaqib Zaid G , Rayis Mohammed , Alharbi Musa 
Published: June 2024

Abstract

BACKGROUND
Medulloblastoma (MB) is the most common childhood malignant brain tumor treated with intensive multimodalities therapy including Surgery, Craniospinal Radiation, and chemotherapy. Our study aims to document the clinical courses, prognostic factors, and survival outcomes in Saudi children above three years with Medulloblastoma treated in King Fahad Medical City KFMC.

METHODS
Retrospective analysis of MB patients diagnosed between January 2009 to January 2022 All patients received Risk-adapted Radiation therapy followed by maintenance chemotherapy,3 patients progressed and died after surgery and were excluded from analysis.

RESULTS
We identified 145 MB patients 65.5 % were male. median age at Diagnosis 7.00 years (range3-14 years), Age less than 5 years did not have a worse outcome in our cohort. Classic histology was predominant (80%), 42.1% of patients had metastatic disease at presentation; the Median time to start radiation therapy after surgery was 35 days. 51.7% were treated as High-Risk HR MB and Average Risk AR MB 48.3%. 65 cases having molecular testing for MB molecular subgroups. 6 patients 4.1% developed a second malignancy with a median time of 6 years post diagnosis. Multivariate survival analysis showed that progression-free survival was significantly reduced by the extent of surgical resection (P=0.021) and Metastatic MB at diagnosis(P=0.014). At Median follow-up of 7 years, Progression-free survival PFS and overall survival OS for the whole cohort were 72.4% and 71.7% respectively. PFS for AR MB and HR MB was 81.4% and 64.0% respectively. PFS analysis based on molecular subgroup: WNT subgroup 92.3%, SHH 69.2%, Group 4:57.7%:and group 3: 46.2%.

CONCLUSIONS
Our study is the largest analysis of childhood MB treatment outcomes in Saudi Arabia Defining the poor prognostic factor for these patients and will form the baseline for future pediatric Neuro-Oncology studies in KFMC, which may help to improve the outcome of childhood MB in Saudi Arabia.
LMIC-06. WEB-BASED SURVEY RESULTS OF THE INTERNATIONAL PEDIATRIC NEURO-ONCOLOGY TUMOR BOARD AT WASHINGTON UNIVERSITY IN ST. LOUIS SCHOOL OF MEDICINE
Authors: Shatara Margaret , Rocco Abbey , Cluster Andrew , Brossier Nicole M , Armstrong Amy E , Hirbe Angela C , Gutmann David H , Abdelbaki Mohamed S 
Published: June 2024

Abstract

BACKGROUND
The International Pediatric Neuro-Oncology Tumor Board at Washington University in St. Louis School of Medicine (WUSM) was established in January 2021 as a monthly multi-disciplinary collaboration to help guide the care of pediatric central nervous system (CNS) tumor patients worldwide. The quarterly integration of Neurofibromatosis (NF) meetings expanded the initiative in September 2021. This survey explores participant experiences and their satisfaction aiming to optimize this international collaboration.

METHODS
A cross-sectional survey was distributed via a web-based platform in September 2023 amongst the participating healthcare professionals.

RESULTS
Fifty-three respondents from 23 countries completed the survey. The majority identified as pediatric hematology-oncologists (59%), and 10% as neuro-oncologists. Ninety-eight percent attended at least one session over two years, and 71% actively engaged in the quarterly NF meetings. Sixty percent attended more than five meetings, and 29% engaged in over 10 meetings. Barriers to attendance were primarily attributed to time constraints (71%) and conflicting professional or personal experiences (27%), while only 7% cited technical limitations and lack of awareness. Ninety-one percent reported that the meetings provide valuable educational insights and knowledge, particularly addressing challenging pediatric neuro-oncology cases. Additionally, 95% acknowledged the tumor board meetings’ positive contribution to professional development. Consensus recommendations emerging from the tumor board were reported to align with institutional recommendations (71%), be clear and comprehensible (93%,) and led to improved outcomes (93%). Notably, meeting frequency, leader expertise, knowledge enhancement, and level of engagement had positive influence on the participants’ willingness to attend the meeting.

CONCLUSION
Healthcare professionals attending the WUSM International Pediatric Neuro-Oncology Tumor Board reported the effectiveness of this virtual meeting format, its impact on professional development, and the alignment of recommendations with diverse institutional needs. The study provides valuable insights to further enhance the program’s sustainability, international collaboration, and overall effectiveness in improving global pediatric neuro-oncology patient care.