bluuebunny/crossref_metadata_2025 huggingface dataset:
NURS-03. NEED FOR PROGRAMS FOCUSING ON CAREGIVERS FOR YOUNG ADULT SURVIVORS OF CHILDHOOD BRAIN TUMORS
Authors: Deatrick Janet A , Joseph Melanie , Herchline Emily , Hammer Shannon , Anil Ashley , Ramaswamy Nithya , Hobbie Wendy , Minturn Jane E , Barakat Lamia P
Published: June 2024

BACKGROUND

The physical, emotional, social, developmental, and economic risk experienced by survivors of childhood brain tumors and their families is well documented, as is the acceleration of those risks as survivors transition into young adulthood. Further, the impact of the lack of services in the community is compounded by insufficient investigation of interventions to support survivor functioning and their caregiver’s management of their medical and psychosocial needs.The purpose of this study was to describe maternal caregivers’ perspectives about key components of potential interventions to support maternal caregivers of young adult survivors of childhood brain tumors.

METHODS

Data were obtained from 21 at-risk maternal caregivers (based on the Family Management Style Measure) of young adult survivors aged 18-29 years old who were not partnered, were presently living at home, and who participated in a pilot randomized trial Training in Problem Solving (TIPS) for Caregiver of Young Adult Survivors of Childhood Brain Tumors. Caregivers were interviewed using a semi-structured qualitative interview guide constructed using the Consolidated Framework for Implementation Science. Codes, categories, then themes were identified by means of directed content analysis.

RESULTS

All caregivers agreed these services were absent and the most effective timing would be at the transition to survivorship with ongoing follow-up. Key components of potential interventions identified by maternal caregivers were skill-building, motivational interviewing to increase readiness to change long-standing patterns of family management, use of validation of their efforts as parents and caregivers to build confidence in trying new approaches and shifting their perspectives on ongoing caregiving for a childhood brain tumor survivor to find hope in even small changes.

CONCLUSIONS

Caregivers endorsed the importance of targeted psychosocial support throughout survivorship for caregivers within the context of their family, facilitating their roles as both parents and caregivers to young adult childhood brain tumor survivors.
NURS-10. DEVELOPMENT OF A NATIONAL PAEDIATRIC NEURO-ONCOLOGY NURSES GROUP (UNITED KINGDOM)
Authors: McAndrew Rachel , Laughlin Elizabeth , Page Joanne , Paisley Helen , Howat Angela , Coyle Paul
Published: June 2024

BACKGROUND

The purpose of developing this group is to provide neuro-oncology patients with a high standard of care from diagnosis, treatment and beyond that is research based and reflects individual needs. This forum allows nurses working within paediatric neuro-oncology to share knowledge, experience, collaborate on projects, benchmarking and research opportunities. This will allow paediatric neuro-oncology nurses to increase their expertise and to foster relationships and collaborate with the wider neuro-oncology field and multi-disciplinary team.

METHODS

Develop an affiliation with a national association or organization Develop links to ensure all neuro-oncology nurses within CCLG centres are aware of the group, have the opportunity to join, fostering collaboration and support. Develop awareness of the neuro-oncology nursing speciality Develop a mission statement, terms of reference, and rolling agenda Literature reviews to ensure group has similar operation in line with other national nurses’ groups. Developing accountability.

RESULTS

Developed database of national neuro oncology nurses with all CCLG UK and Ireland centres represented. Set frequency of meetings and agendas. Ensure it operates to the same standard as other nurses’ groups. Organised working groups for projects. Agreed role of chair.

CONCLUSION

These activities have continued the development of the group since it’s conception in 2015 providing more structure, continued support to its members and wider recognition of its work. A robust mission statement, terms of reference, organisation and structure will ensure continued provision of education and support to neuro-oncology nurses, recognition of the group to the wider neuro-oncology community and improve overall patient experience.
NURS-16. CREATING A STANDARDISED DOCUMENT FOR EDUCATION SETTINGS ACROSS THE UNITED KINGDOM FOR CHILDREN WITH CENTRAL NERVOUS SYSTEM TUMOURS
Authors: Hayes Melissa , Blount Nicola , Robinson Louise , Reynolds Gabrielle , Ryles Jade
Published: June 2024

There are currently nineteen Principle Treatment Centres (PTC) in the UK delivering care to children, aged 0-19, following diagnosis of a Central Nervous System (CNS) tumour. Every centre promotes inclusivity and the safe and successful return to education, however reintegration can be a challenging process for this complex group of patients and there is a vast amount of information available. At present each PTC provides their own personalised document, including a list of resources, to signpost the education setting to appropriate information. With the collaboration of participating PTC’s, our aim was to create a standardised document for education settings to utilise following a child’s CNS diagnosis. Each of the nineteen PTC’s were approached, requesting representation from a neuro oncology nurse specialist and the sharing of their bespoke information. Following this, benchmarking criteria were created and each document reviewed and evaluated. The review and evaluation process also included websites and information leaflets that centres currently signpost to, from charities and other relevant organisations. By working closely together as a national group of neuro oncology nurses, we have created a standardised document and list of suitable resources for education settings. The finalised document will be shared with each PTC, with the intention of promoting a smooth transition back into education and quality and equity of information for all children, irrespective of where they live in the UK. Auditing of the document will be part of the ongoing work of the group.
NURS-21. EXPLORATION OF CORRELATIVE STUDIES IN EARLY PHASE TRIALS FOR PEDIATRIC AND YOUNG ADULT CENTRAL NERVOUS SYSTEM (CNS) TUMORS AND THE POTENTIAL TRANSLATION TO CLINICAL CARE
Authors: Seidl Ken , Briamonte Courtney Baker , Higgins Micah , Hoffman Carly , Holtzlaw Susan , McHugh Michele , Meyer Ashley , Rangan Kasey , Schmus Cindy , Strachan Marylynne , Waters Kaaren , Yeh-Nayre Lanipua , Kline Cassie , Prados Michael , Mueller Sabine , Raber Shannon
Published: June 2024

BACKGROUND

Correlative studies are common in early phase clinical trials. In addition to primary aims establishing maximum tolerated dose or efficacy, supplementary information from biospecimens is frequently collected with patient consent. The Pediatric Neuro-Oncology Consortium (PNOC) has included several correlative studies with implications for understanding patterns in the development of tumors, response to treatment, and prognosis. A needs assessment survey of PNOC institutions by the Advanced Practice Provider and Investigational Nurse Committee (APPNIC) highlighted that nurses and advanced practice providers (APPs) desire further education regarding correlative studies.

METHODS

Blood, stool, cerebrospinal fluid (CSF) and hair strands are examples of correlative biospecimens incorporated in PNOC protocols. We will share a review of the literature and implications for practice.

RESULTS

Blood, drawn in conjunction with clinical labs, is commonly analyzed for circulating tumor DNA to conduct molecular profiling in blood compared to tissue, explore less invasive means of molecular evolution of tumor somatic mutations, and identify early markers of tumor response or resistance. Stool is collected to utilize the gut microbiome as a lens into treatment response in CNS tumors via the gut-brain axis. Stool samples are compared to normal controls and longitudinally within patients during treatment. CSF sampling provides less invasive disease monitoring, tumor molecular characterization, markers of tumor response or resistance, and drug pharmacokinetics. Hair sampling can be used to further quantify drug levels for pharmacokinetics and assess treatment compliance. The robustness of these correlative samples collected at various timepoints (diagnosis, pre-surgery and post-surgery, post-radiation and/or with recurrence) informs on prognosis, response to treatment; and ultimately, interventions to improve outcomes for pediatric and young adult CNS tumors.

CONCLUSION

Our assessment identified a need for APP and nursing-focused education on biospecimen collection to inform on emerging clinical and research advances while improving protocol compliance.
OTHR-01. ALK-DRIVEN INFANT-TYPE HEMISPHERIC HIGH-GRADE GLIOMA AND CNS HISTIOCYTOSIS SUCCESSFULLY TREATED WITH A SECOND GENERATION ALK-INHIBITOR: MOLECULAR CHARACTERIZATION SAVES THE DAY
Authors: Chamdine Omar , Alotaibi Rasees , Alharbi Qasim , Altarrah Hiba , Abduljabbar Lulwah , Alzaher Asrar , Taha Mahmoud , Alsaiari Sultan , Alisawi Wissam , AlSadeq Jalilah , Abdulkader Marwah , Alhaddad Fatima
Published: June 2024

BACKGROUND

Molecular characterization of brain tumors (BT) is increasingly becoming essential for diagnosing and managing central nervous system (CNS) tumors. Infant BT is a particular category of pediatric CNS tumors that poses a challenge to the neuro-oncologist.

METHODS

Here, we present two distinctive cases where molecular characterization significantly influenced diagnosis, management, and outcome.

RESULTS

The first case is a 2-year-old boy presented with generalized seizures. MRI of the brain showed multiple dural-based tumors. Biopsy was consistent with ALK-positive histiocytosis (KIF5B-ALK fusion). Additional lesions were detected in the right kidney and left femoral head. Despite three months of LCH-based therapy, the tumor progressed. Chemotherapy was halted, and treatment with alectinib was initiated. Follow-up MRIs after 3 and 6 months showed marked regression and a complete resolution of the lesions, respectively. The second case is a 12-month-old boy who exhibited developmental regression and increased head circumference over the past three months. MRI revealed a large complex right ventricle mass measuring 8.6x7.2x8 cm. Subtotal resection was complicated by severe intracranial bleeding, requiring prolonged intensive care stay. The initial pathological diagnosis was anaplastic ependymoma. He received two cycles of neoadjuvant chemotherapy followed by a second look surgery, which failed to achieve a gross total resection. Molecular testing by this time identified an ALK-CCDC85A fusion, altering the diagnosis to infant-type hemispheric glioma. He was started on alectinib. MRI after 3 and 6 months showed a favorable response with an overall improvement in his cognitive function. Both patients tolerated alectinib well, remaining on therapy for 6 and 12 months, respectively. No toxicities were reported.

CONCLUSION

These cases illustrate the transformative role of molecular characterization in managing infants with CNS tumors, highlighting its potential as a game-changer in pediatric neuro-oncology.
OTHR-03. DEVELOPMENT OF PANORAMA: AN ASSESSMENT TOOL FOR PEDIATRIC NEURO-ONCOLOGY SERVICE DELIVERY CAPACITY
Authors: Rajagopal Revathi , Diaz-Coronado Rosdali , Hamid Syed Ahmer , Campo Regina M Navarro-Martin del , Boop Frederick , Bag Asim , Reséndiz Alma Benito , Bhat Kalya Vasudeva , Campos Danny , Chang Kenneth T E , Cirt Ramona , Rahmartani Ludi Dhyani , Foo Jen Chun , Hoveyan Julieta , Lucas Jr. John T , Ngcana Thandeka , Ain Rahat Ul , Omran Nuha , Osorio Diana , Qureshi Bilal Mazhar , Sabin Noah , Schandorf Ernestina , Bankah Patrick , Dadzie Mary-Ann , Gbadamosi Hafisatu , Sharafeldin Hend , Somathilaka Mahendra , Yang Peiyi , Jean-Jacques Yao Atteby , Zhang Anan , Salman Zeena , Gonzalez Miriam , Friedrich Paola , Qaddoumi Ibrahim , Moreira Daniel C
Published: June 2024

BACKGROUND

To enhance the quality of care available for children with central nervous system (CNS) tumors across the world, a systematic evaluation of service delivery capacity is needed to identify gaps in pediatric neuro-oncology and prioritize interventions. To that end, we created the PediAtric Neuro-Oncology Resource AssesMent Aid (PANORAMA) tool.

METHODS

PANORAMA development consisted of three phases: operationalization, consensus building, and piloting. PANORAMA was designed to have domains that capture the elements of the pediatric neuro-oncology care continuum using assessments which were weighted according to their importance. Responses were ordinally scored to reflect adequacy of satisfaction. PANORAMA was revised based on feedback at various phases to improve its relevance, usability, and clarity.

RESULTS

The operationalization phase identified thirteen domains using 252 questions. The consensus phase included validating the identified domains, questions, and scoring by fifteen experts (six pediatric oncologists, three radiation oncologists, two neurosurgeons, two radiologists, and two pathologists). The validated PANORAMA domains were national context, hospital infrastructure, organization and service integration, human resources, financing, laboratory, neurosurgery, diagnostic imaging, pathology, chemotherapy, radiotherapy, supportive care, and patient outcomes. Seventy-six questions were added during the expert review. PANORAMA was piloted at thirteen institutions in twelve countries, representing diverse patient care contexts. Face validity was assessed using the correlation between the estimated score by respondents and calculated PANORAMA scores for each domain (r = 0.67, p <0.0001). Piloting eliminated two questions.

CONCLUSIONS

PANORAMA was developed following a systematic approach, leading to a relevant tool to evaluate the core elements of pediatric neuro-oncology service capacity. PANORAMA will be distributed to facilitate quantitative evaluation of institutional services, allowing for prioritization and benchmarking with centers at the local, regional, and international levels.
OTHR-30. THE CLINICAL AND BIOLOGICAL LANDSCAPE OF CNS CANCERS IN CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY: AN IRRDC COHORT STUDY
Authors: Ercan Ayse Bahar , Aronson Melyssa , Fernandez Nicholas R , Chang Yuan , Liu Zhihui Amy , Negm Logine , Edwards Melissa , Bianchi Vanessa , Villani Anita , Malkin David , Hawkins Cynthia , Bouffet Eric , Das Anirban , Tabori Uri
Published: June 2024

BACKGROUND

Constitutional mismatch repair deficiency (CMMRD) is an aggressive cancer predisposition syndrome. As a lack of data contributes to management challenges and inferior outcomes, especially in central nervous system (CNS) cancers, we aimed to determine the clinical spectrum, cancer biology, and impact of genetics on patient survival.

METHODS

To determine the cancer spectrum, biology, estimated incidence, and impact of genotype on cancer onset and survival, including following surveillance and immunotherapy, we collected cross-sectional, longitudinal, and genomic data on CMMRD patients and their cancers registered to an international consortium.

RESULTS

We report 201 patients enrolled between 2007-2022 (median follow-up: 7.2 years). Overall, 194 (97%) patients developed 339 cancers. Cumulative cancer and CNS tumor incidence were 93% and 82% by age 20, respectively. Median time between cancers was 2 years. Although neoplasms developed in 15 organs and included early-onset adult cancers, CNS tumors had the earliest median age of diagnosis (9.7 years), were the most common cancer type (51%), and the main cause of death (p<0.0001). All cancers exhibited high mutation and microsatellite burden, and pathognomonic mutational signatures. CNS cancers were enriched for mutations in POLE/POLD1, TP53, IDH1, and RAS/MAPK compared to hematopoietic and other cancers. These mutations determined response to therapy. Germline MLH1/MSH2 variants caused earlier cancer and CNS tumor onset than PMS2/MSH6, and inferior survival (survival at 15 years: PMS2: 63%, MSH6: 49%, MLH1: 19%, MSH2: 0%, p<0.0001). Strikingly, frameshift/truncating variants within the same gene caused earlier cancers and inferior outcomes (p<0.0001). The deleterious impact of MLH1/MSH2 persisted despite overall improvement in survival following surveillance and immunotherapy.

CONCLUSION

The extreme cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis focusing on specific genotypes to perform precision approaches toward surveillance and immunotherapy. These data will guide the management of children and emerging adult survivors of CMMRD.
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

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<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

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

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 (>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 (>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

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

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

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

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>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

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

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.
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

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 <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

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

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.