bluuebunny/crossref_metadata_2025_split huggingface dataset:
NURS-19. IMPLEMENTING A NURSING LED WORKING GROUP WITHIN THE PEDIATRIC NEURO-ONCOLOGY CONSORTIUM (PNOC), A TWO-YEAR EXPERIENCE AND EVALUATION
Authors: Raber Shannon , Hoffman Carly , Kline Cassie , Mueller Sabine , Prados Michael , Meyer Ashley 
Published: June 2024

Abstract

BACKGROUND
Incorporation of nurses and advanced practice providers (APPs) creates an opportunity to enhance the work of clinical trial consortia in providing care to children and young adults with central nervous system tumors enrolled on clinical trials. Within PNOC, a formalized APP and nursing working group (“APPNIC”) was established in 2021. Since inception, APPNIC has assigned members to each clinical trial committee, developed support documents to partner with protocols, highlighted supportive care measures, and provided nursing education across all PNOC sites.

METHODS
A de-identified, electronic Qualtrics survey was distributed to PNOC members in Fall 2023 to evaluate the 2-year impact of APPNIC. Physicians, nurses or APPs, and CRCs were eligible to participate.

RESULTS
Thirty-six surveys were completed in total from physicians or principal investigators (n=15; PIs), nurses/APPS (n=18), and clinical research coordinators (n=3; CRCs) representing multiple institutions. PI satisfaction with APPNIC was high with all reporting APPNIC to be “somewhat helpful” (40%) or “very helpful” (60%) and most PIs (53%) working directly with APPNIC members. Nurses confirmed they use the protocol roadmaps (87%) and education sheets (80%) generated by APPNIC. Barriers to APPNIC participation continue to indicate scarce resources allowing time for APPs and nurses to participate in hybrid meetings and limited travel funds to attend meetings and conferences. Identified education needs of APPs and nurses include identifying supportive care for novel treatments, understanding developmental therapy strategies, and receiving routine study updates.

CONCLUSIONS
With high overall satisfaction of PIs and utilization of study deliverables by consortium site members, we plan to continue APPNIC as currently structured. Ongoing efforts to integrate APPNIC members early in protocol development will increase PI and APPNIC member collaboration. Education for APPs and nursing will continue to be a priority, along with investigating mechanisms to increase funding to attend meetings and conferences.
NURS-20. A PATIENT AND FAMILY EDUCATION PROJECT: COMPREHENSIVE RESOURCE FOR MEK INHIBITOR-INDUCED PARONYCHIA
Authors: Apelquist Jacqueline O’Connell , Burnside Kasey L , Day Sarah , Trinidad Vless , Rangan Kasey , Waters Kaaren , Smith Lara G 
Published: June 2024

Abstract

BACKGROUND
Targeted therapies for pediatric tumors of the central nervous system have recently brought promising results as well as new challenges in the clinical management of these patients. FDA approval of MEK inhibitors has prompted a significant increase in use of these agents in pediatric neuro-oncology patients. MEK inhibitors are commonly used for treatment of pediatric low and high-grade gliomas, as well being a proven treatment for plexiform neurofibromas. Cutaneous reactions to targeted therapy occur frequently, with paronychia arising in more than half the patients.

METHODS
Despite providing a robust MEK inhibitor skin care in-service at the start of treatment, the multidisciplinary neuro-oncology team identified a need for specific paronychia education for patients undergoing therapy with MEK inhibitors. The education content was developed following a thorough literature review of MEK inhibitors and associated side effects. Evidence-based information was selected to create a clear, concise, one-page educational resource.

RESULTS
The educational flyer addressed five key educational objectives including defining and reviewing paronychia as an expected side effect of MEK inhibitor therapy, discussing strategies for prevention and management of paronychia, and identifying when to contact a healthcare provider for paronychia support. Content included written and pictorial definitions to aid in recognition of paronychia, bulleted list and visual guide for preventive nail maintenance, recommendations and instructions for over-the-counter management strategies, review of therapies that may be prescribed, and specific guidelines on when to seek prompt medical attention. This flyer served as a valuable educational tool, equipping individuals undergoing MEK inhibitor therapy with knowledge about paronychia, prevention, and effective management.

CONCLUSION
MEK inhibitor-induced paronychia is an undesirable side effect that can impact adherence to treatment. By empowering patients and families with this educational resource, healthcare providers may enhance patient engagement, promote adherence to treatment, and optimize quality of life.
NURS-22. NAVIGATING DISPARITIES: COMPREHENSIVE CARE AND ACCESS TO CLINICAL TRIALS FOR ADOLESCENTS AND YOUNG ADULTS WITH CENTRAL NERVOUS SYSTEM TUMORS
Authors: Briamonte Courtney , Holtzclaw Susan , Higgins Micah , Hoffman Carly , McHugh Michele , Meyer Ashley , Raber Shannon , Rangan Kasey , Schmus Cindy , Seidl Kenny , Strachan Marylynne , Waters Kaaren , Yeh-Nayre Lanipua 
Published: June 2024

Abstract

BACKGROUND
Central nervous system (CNS) tumors are one of the most common causes of cancer-related death in the adolescent and young adult (AYA) age group. Despite being a prevalent cancer diagnosis, adolescents and young adults continue to be underrepresented in clinical trials. Literature review shows a notable lack of research focused on clinical care, reproductive health, and psychosocial aspects specific to this population. The longstanding issue of low AYA participation in clinical trials persists across various cancer types, with a particular scarcity of data regarding CNS tumors. Notably, the lack of participation in clinical trials has been associated with worse survival outcomes and increase in frequency and severity of treatment-related toxicity, emphasizing the critical impact of this issue on patients’ overall morbidity and mortality. The literature underscores the under-representation of AYAs with CNS tumors in neuro-oncology trials..

METHODS
This talk will review challenges faced by adolescents and young adults (AYAs) diagnosed with central nervous system (CNS) tumors.We will discuss the necessity for molecular profiling in the diagnostic workup of CNS patients to delineate tumor biology and guide treatment plans, including clinical trial access. To address the insufficient understanding of best practices for this group, there is a crucial call for expanding access to clinical trials. We will explore barriers to clinical trial access and provide case examples of successful and unsuccessful work with AYA patients with CNS tumors with ideas to improve access. Finally, we will discuss the holistic care of AYAs with CNS tumors through a multidisciplinary approach, incorporating expertise in neuro-oncology, oncofertility, palliative care, and psychosocial aspects within both pediatric and adult care settings

RESULTS
N/A

CONCLUSIONS
By the end of this presentation, pediatric RNs and APPs will have an understanding of the differences in caring for this unique population of patients including benefits of enrolling adolescents and young adults with CNS tumors in clinical trials.
OTHR-04. HEALTH SYSTEM DELAYS IN DIAGNOSIS AND TREATMENT OF CHILDREN WITH CENTRAL NERVOUS SYSTEM (CNS) TUMOURS IN SRI LANKA
Authors: Somathilaka Mahendra , Jayathilaka Ashika , Jayasekera Dhanushka , Azwer Mohomad I M , Jayaweera Nilrukshan , Garusinghe Sanjeewa , Jayawickrama Modhini , Constantine Roshana , Gupta Tejpal , Chinnaswamy Girish , Upadhyaya Santhosh , Salman Zeena , Qaddoumi Ibrahim , Gunasekera Sanjeeva 
Published: June 2024

Abstract

BACKGROUND
Children with central nervous system(CNS) tumours have to navigate multiple layers of care to reach the only centre providing oncology care (chemotherapy and radiotherapy) in Sri Lanka. This can lead to significant delays and affect outcomes.

METHODS
This is a retrospective study of patients less than 19 years registered at the National Cancer Institute Sri Lanka(NCISL) from 1st January 2022 to 31st December 2023. Data was extracted from clinic records and interviewing caregivers.

RESULTS
From a total of 828 new children with cancer 135 had CNS tunours and data was available for 130 for analysis. Commonest cancers seen were low grade gliomas and medulloblastoma. Fifty-one percent were males and the median age was 6 years (Range 1-18). Most common presenting symptoms were headache and vomiting. Median time from onset of symptoms to first medical contact was 4 days (InterQuartile Range(IQR) 1-9.5) and to first imaging it was 44 days (IQR 3-151) for all symptoms. In the presence of neurological symptoms, the time to imaging was 26 days (IQR 2-141). Ninety-six(74%) had upfront surgery at a median time 14 days from first imaging (IQR 7-34.5) with a median time of additional 25 days to reach an oncology centre (Range 7-94). Patients who did not have upfront surgery took 13.5 days (IQR 2-36.5) for the same. After arriving at the oncology centre, radiotherapy (80/130, 62%) was initiated in 24 days. When calculated from date of surgery radiotherapy initiation time was 61 days. (Range 5-88)

CONCLUSION
Although there seem to be no significant delay in presentation of children with CNS tumours to the health system, there were significant delays in imaging and initiating adjuvant radiotherapy. Further studies are warranted to determine the attributing factors and corrective steps to be taken to expedite referral of affected children.
OTHR-07. LIFE THREATENING CATATONIA AND THE USE OF ELECTROCONVULSIVE THERAPY IN A PATIENT WITH RELAPSED MEDULLOBLASTOMA
Authors: Chaleff Stanley , Gerwin Roselyn , Wolfrum Lee , Bokat Pamela , Kastle Nadav 
Published: June 2024

Abstract
Medulloblastoma is one of the most common malignant brain tumors in the pediatric population and with multimodal therapy the majority of patients will be cured, but patients experience significant morbidity related to the disease and therapy. Catatonia is a life-threatening psychomotor disorder that has rarely been described in the pediatric population and is likely under recognized. Catatonia is a treatable condition using benzodiazepines as first line with electroconvulsive therapy (ECT) used for patients who do not respond or have life threatening malignant catatonia. In the medical literature there are very few papers to inform on the safety of using ECT in patients who have received radiation in the past or are undergoing chemotherapy. We describe a patient in remission of his medulloblastoma who presented with refractory catatonia who needed lifesaving ECT, then had metastatic recurrence of his medulloblastoma. The patient was initially diagnosed with group 4 medulloblastoma at 14 – he was treated with high-risk therapy to metastatic sites of disease at diagnosis as per COG ACNS 0332 with a combination of surgery, chemotherapy and craniospinal radiation and a boost to the primary tumor and metastatic sites of disease. Approximately 18 months after the end of therapy he was diagnosed with treatment refractory catatonia and needed to be started on ECT with a good response. 6 months after presentation of catatonia, the patient unfortunately had a relapse of his medulloblastoma in his left temporal lobe and is now actively getting ECT and chemotherapy at the same time without complications. The description of this patient will add to the sparse body of evidence that it is likely safe to be able to deliver chemotherapy at the same time as ECT.
OTHR-14. AN ADOLESCENT WITH A RARE SCHWANNOMA LOCALIZATION AND THE IMPORTANCE OF METHYLATION STUDIES
Authors: Luz Inês Romão , Gonçalves Raquel , Sousa Rita , Carvalho Sílvia , Novo Ana Margarida , Rebelo Olinda , Pinheiro João , Soares Gustavo , Frank Stephan , Hench Jürgen , Carvalho Alice 
Published: June 2024

Abstract

BACKGROUND
Schwannomas are benign nerve sheath tumours, accounting for about 8% of intracranial tumours, with different histologic patterns described. Olfactory nerves are not expected to have Schwann cells, several theories exist about the origin of these tumours.

METHODS/RESULTS
A 16-year-old boy was admitted to the emergency department due to a first, self-limited, isolated epileptic event. He scored 15 in the GCS and no focal neurological deficits were observed. At that time, he complained about headaches, lasting for 3 months. Brain CT showed a frontobasal heterogeneous mass. MR characterized it as a 43X34X38 mm well-circumscribed mass, with solid and cystic areas, having an intimate relationship with lamina cribosa, with extensive vasogenic oedema surrounding it, causing deviation of adjacent structures. At that time, he was COVID-19 positive. He was submitted to a craniotomy with a transcortical approach, with an apparent total resection. Retrospectively, he became aware of an improved sense of smell after intervention. The histopathological study revealed a tumour composed of sheets and lobules of large, round cells showing immunopositivity for SOX-10 and S100 and with a Ki-67 index of 5-6%. We proceed to a molecular diagnosis, as the morphology was elusive, finding a methylation pattern highly close to those of schwannomas. With this presumptive diagnosis, clinical and radiological follow-up has been done. After two years, he is doing well, without signs of recurrence.

CONCLUSIONS
Although rare, an olfactory nerve schwannoma should be considered when there is a frontobasal tumour and impaired sense of smell, although in this case, the COVID-19 infection could be responsible for hyposmia. The clinical picture, imaging and histopathology description were not enough to make the diagnosis and, therefore, to plan the post-surgical approach. We emphasize the importance of a comprehensive molecular study, with a methylation classifier, as this tumour exhibits a typical DNA methylation pattern.
OTHR-22. SUCCESSFUL DEVELOPMENT OF RESOURCES FOR DMG/DIPG PATIENT FAMILIES THROUGH A NETWORK OF FAMILIES, RESEARCHERS, AND CARE TEAMS
Authors: Lyons Nicole , Ward Lisa 
Published: June 2024

Abstract
The DIPG community has been severely affected by a lack of resources and awareness due to the relative rarity of the disease. In recent years, this has led to a network of patient families, researchers, and clinicians who have worked together to develop resources that improve clinical care, research, and patient family support. These resources address issues in care equity such as access to clinical trials, accurate information, and consults with leading physicians in the field. These initiatives span across multiple institutions and are predominantly little to no cost for the families. This relationship is mutually beneficial; data from patient families inform researchers and clinicians. In turn, researchers and clinicians use these findings to support other families. Over the last five years, many of the resources developed and/or utilized by the DIPG community have been successful. Since May 2021, 42% of post-mortem tissue donations through Gift From a Child have been DIPG or DMG. Data from this tissue is shared openly through the Children’s Brain Tumor Network, ensuring that a diverse patient population is represented in future research projects. DIPG One-link helps patient families navigate vetted resources for care at any point after diagnosis. Resources include patient navigators, information about research and clinical trials, emotional and grief support, places to safely share their data, and referrals to the DIPG/DMG National Tumor Board. All of these resources have shown an overall increase in use since implementation. There has also been an increase in access by patient populations and care teams that previously would have been unable to access such important resources. The direct involvement of patient families ensures that patient voices are represented and valued. These resources are essential to removing institutional, financial, geographic, and health literacy barriers, and ensuring all future patients have equitable access to care.
OTHR-26. MINIMALLY-INVASIVE MOLECULAR DIAGNOSIS OF DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT) USING CEREBROSPINAL FLUID CELL-FREE DNA SEQUENCING IN PEDIATRIC AND YOUNG ADULT PATIENTS
Authors: Larsen Alexandra M Giantini , Hill Katherine , Hickman Richard , Bale Tejus A , Holle Bridget , Mellinghoff Ingo , Dunkel Ira , Souweidane Mark , Greenfield Jeffrey , Sait Sameer Farouk , Miller Alexandra M , Karajannis Matthias A 
Published: June 2024

Abstract

BACKGROUND
Diffuse leptomeningeal glioneuronal tumor (DLGNT) presents with nodular leptomeningeal disease throughout the neuroaxis and is characterized by the presence of KIAA1549::BRAF fusion and chromosome arm 1p deletion. Concomitant gain of chromosome arm 1q is associated with poor prognosis. Diagnosis by meningeal biopsy is often non-diagnostic due to sampling error or yields insufficient material for molecular testing. We hypothesized that analysis of cell free DNA (cfDNA) from cerebrospinal fluid (CSF) could represent a superior diagnostic modality.

METHODS
We analyzed CSF samples from 9 suspected DLGNT patients, median age of 19.5 years with a 5:4 male:female ratio using MSK-IMPACT, a hybridization capture-based next-generation DNA sequencing panel, including matched germline.

RESULTS
Prior tissue biopsy was done in 7 patients; 6 were negative for the KIAA1549:BRAF fusion and 1 was positive. Of the 6 biopsies negative for the fusion, analysis of CSF cfDNA detected KIAA1549::BRAF fusion in 3/6 (50%) of patients, who were all subsequently started on MEK inhibitor therapy. The other 3 patients were negative for KIAA1549:BRAF fusion on both biopsy and CSF cfDNA. One patient received biopsy confirmation of KIAA1549::BRAF fusion after CSF cfDNA analysis detected the mutation. In addition, in one patient with prior tissue-confirmed KIAA1549::BRAF fusion, the fusion was not detected in CSF cfDNA during/after treatment with a MEK inhibitor, but additional somatic alterations and DNA copy number profiles were similar to those found in prior biopsies. Additional somatic alterations were identified in ATRX, BCOR, RARA, STAT5A, SPOP, PPM1D, MED12, KMT2C, RECQL andSETD2, including likely oncogenic secondary driver alterations that have not been previously reported in DLGNT.

CONCLUSIONS
Given the high molecular diagnostic yield and concordance with open biopsy, cfDNA CSF sequencing should be considered as a first line diagnostic maneuver for patients with suspected DLGNT, followed by surgical biopsy only if CSF testing is non-diagnostic.
PATH-03. FOXR2-OVEREXPRESSING CENTRAL NERVOUS SYSTEM (CNS) TUMORS EXHIBIT SUBSTANTIAL DIVERSITY ACROSS HISTOLOGICAL, MOLECULAR, AND CLINICAL DIMENSIONS
Authors: Hanzlik Emily , Siskar Alexa N , Eldomery Mohammad K , Pinto Soniya , Tinkle Christopher L , Zhang Qunyu , Cardenas Maria F , Dhanda Sandeep K , Li Xiaoyu , Robinson Giles W , Wheeler David A , Blackburn Patrick R , Chiang Jason 
Published: June 2024

Abstract

BACKGROUND
FOXR2 activation is regarded as the pathognomonic molecular signature of CNS neuroblastoma. However, a comprehensive understanding of the landscape for CNS tumors exhibiting FOXR2 activation is lacking.

METHODS
Integrated histopathologic, molecular, and clinical data analysis of 36 FOXR2-overexpressing CNS tumors identified through screening of an institutional dataset.

RESULTS
FOXR2-overexpressing CNS tumors showed a broad anatomic distribution throughout the neuraxis. Of the 36 tumors, 17 (47.2%) were gliomas and 17 (47.2%) were embryonal tumors. The gliomas included 16 high-grade gliomas (eight histone H3 K27M-mutant diffuse midline gliomas, seven radiation-associated tumors, and one with MN1::PATZ1 fusion) and one pilocytic astrocytoma. The embryonal tumors included ten CNS neuroblastomas, six pineoblastomas, and one medulloblastoma. Two were difficult-to-classify high-grade neuroepithelial tumors. The gliomas and embryonal tumors demonstrated comparable FOXR2 expression based on normalized RNA-sequencing data. FOXR2-overexpressing gliomas, but not embryonal tumors, displayed diverse concomitant genetic alterations. The most common mechanisms of FOXR2 activation involved structural alterations leading to proximity effects, frequently incorporating non-canonical non-coding exons, followed by activation of the exon -3 promoter. Tumor location, histology, and concomitant alterations correlated with patient outcomes. While FOXR2-overexpressing gliomas were aggressive with a 5-year overall survival of 13.3%, FOXR2-overexpressing embryonal tumors showed a diverse prognosis. FOXR2-activated CNS neuroblastoma showed a 5-year overall survival of 100%. Pineoblastomas with FOXR2 activation in the PB-FOXR2 DNA methylation group showed a 3-year survival of 0% despite multimodal therapy. The one medulloblastoma patient in the cohort is alive at three years post-diagnosis.

CONCLUSION
FOXR2-overexpressing CNS tumors manifest significant histological, molecular, and clinical diversity and can occur as post-radiation tumors. Glioma histology and concomitant genetic alterations correlate with treatment resistance and inferior prognosis, while FOXR2-overexpressing embryonal tumors show more heterogeneous outcomes. Integrating histologic and molecular diagnostic approaches along with therapeutic interventions and clinical outcomes is imperative for accurate prognostication and optimal therapeutic decision-making.
PATH-05. MACHINE LEARNING-BASED CYTOLOGICAL ANALYSIS OF CEREBROSPINAL FLUID IN MEDULLOBLASTOMA
Authors: Maack Lennart , Kresbach Catena , Neumann Julia , Tischendorf Jacqueline , Wefers Annika , Seegerer Philipp , Schüller Ulrich , Schlaefer Alexander , Bockmayr Michael 
Published: June 2024

Abstract

BACKGROUND
Metastatic dissemination occurring via the cerebrospinal fluid contributes to the poor prognosis in many medulloblastoma patients. It has high prognostic relevance, and its accurate detection is critical for adequate therapy stratification. However, cytological examination is a difficult, time-consuming task and frequently unreliable. We, therefore, propose a machine-learning pipeline to solve this diagnostic challenge.

METHODS
A dataset of 303 digitized images of cerebrospinal fluid preparations from 81 medulloblastoma patients was assembled. Based on these data, over 50000 digitized objects, including more than 5000 patches with tumor cells, were classified by experts into 13 clinically relevant diagnostic categories and used for training. The classification was performed using convolutional neural networks, trained with nested-cross validation and different transfer learning strategies.

RESULTS
The classification into the 13 diagnostic categories was feasible, with an overall accuracy of 75% on the test set and a tumor-specific F1 score of 89%. Most misclassifications occurred between morphologically similar cell types, mainly lymphocytes and activated lymphocytes, monocytes and activated monocytes, as well as tumor cells and atypical cells with borderline cytomorphology. Grouping these cytologically and/or biologically closely related groups increased the overall accuracy to 91%. Pretraining on published cytological datasets of cerebrospinal fluid and bone marrow further increased classification accuracy.

CONCLUSIONS
Deep learning can reliably detect tumor cells in digitized cytological images from cerebrospinal fluid preparations in medulloblastoma. Implementing explanation methods, an easy-to-use user interface and validation on additional cohorts will further strengthen the robustness of the presented approach.