bluuebunny/crossref_metadata_2025 huggingface dataset:
SURG-09. Hypothalamic involvement in pediatric craniopharyngiomas;how to define and to realize optimal neurosurgical resections
Authors: Hoving Eelco , van Baarsen Kirsten , van Schaik Jiska , van Santen Hanneke
Published: June 2022

The optimal neurosurgical strategy for pediatric craniopharyngiomas is on debate with shifts from gross total resection to limited resections in combination with local radiotherapy. The most relevant question underlying this ongoing discussion is how to prevent additional surgical morbidity to the hypothalamus. Limited neurosurgical resection in combination with local radiotherapy has been proved a safe alternative to gross total resection concerning tumor control. Pre-operative anatomical grading of hypothalamic involvement has been proposed by Puget et al using MRI discriminating between no hypothalamic involvement (grade 0), hypothalamic displacement (grade 1), and hypothalamic disruption (grade 2). Subsequently, post-operative hypothalamic damage can also be assessed on post-op MRI by the grading of the Vile et al in no discernable damage (grade 0), abnormality of floor of third ventricle (grade 1), or damaged or deficient floor of third ventricle (grade 2). Three questions remain to be settled: 1. How to define pre-operatively the extent of resection 2. How to realize per-operatively the intended limited resection, and three. How to determine post-operatively the (additional) surgical damage to the hypothalamus. We retrospectively evaluated a series of 25 children with craniopharyngioma being resected in our center from June 2018 until January 2022, with pre- and post-operative grading of hypothalamic involvement. In total 11 patients were downgraded on the post-operative compared to the pre-operative scale; either by 1 grade (n=6) or by 2 grades (n=5). These findings illustrate that the preoperative grading score does not always represent the actual hypothalamic involvement. This complicates the definition of limited surgery pre-operatively and illustrates the importance of both how to integrate per-operative findings in the realization of the intended limited resection and how to evaluate hypothalamic damage caused by tumor growth versus neurosurgical intervention. A more detailed treatment algorithm will be discussed.
SURG-10. Pediatric PF-A ependymoma: a case series of cytogenetics and progression-free survival
Authors: Sharma Shelly , Colliander Reid , DeCuypere Michael
Published: June 2022

Ultra-high risk PF-A ependymoma, defined as 6q chromosome deletion in the setting of 1q gain, represents a biologically unique entity. These tumors are associated with significantly worse progression-free survival and 6q loss is an independent predictor of overall survival. Here, we present cytogenetics and progression-free survival from all PF-A ependymomas diagnosed at Lurie Children’s Hospital of Chicago over a 10-year period (2011 and 2021). Twelve patients were identified with the diagnosis of PF-A ependymoma (42% males, average age at diagnosis 5.75 years) during the study period. Four patients demonstrated gain of 1q on methylation profiling. Two patients with a gain of 1q also had a deletion of 6q, carrying the ultra high-risk designation. All patients underwent surgical resection and post-operative radiation therapy. Patients who received chemotherapy had a significant increase in overall number of surgical resections (p-value < 0.0001). Patients without 1q gain had an average of 2.1 surgeries, while patients with 1q gain had an average 2.75 surgeries. Patients with 1q gain and 6q deletion had an average of 3.5 surgeries. All patients with 1q gain had recurrence of their tumor, compared to 38% of patients without 1q gain. In this series, progression-free survival for the PF-A without 1q gain, 1q gain, and 1q gain with 6q deletion cohort was 27.9, 18.4, and 19.5 months, respectively. The most common complications were radiation toxicity and cerebellar dysfunction (ataxia, dysmetria, and gait imbalance). Not surprisingly, complications were more common in those patients undergoing a greater number of subsequent resections. All PF-A ependymomas should be evaluated for 1q gain and 6q deletion, which can be reliably ascertained using cytogenetic markers in routine clinical use. In this series, 1q gain was associated with a decrease in progression-free survival. Only 2 patients were designated ultra high-risk based on cytogenetic analysis.
SURG-11. Evaluation of surgical results and predictive factors of hydrocephalus in pediatric patients with posterior fossa tumors
Authors: Formentin Cleiton , Matias Leo Gordiano , dos Santos Lucas de Souza Rodrigues , de Andrade Erion Junior , Joaquim Andrei Fernandes , Tedeschi Helder , Ghizoni Enrico
Published: June 2022

INTRODUCTION: Infratentorial tumors represent 45 to 60% of all brain tumors in children and are associated with hydrocephalus in 70 to 90% of cases. The aim of this study is to describe and analyze the surgical results and correlate them with the incidence of hydrocephalus, as well as identify predictive factors of hydrocephalus in patients underwent to a surgical treatment of posterior fossa tumors. METHODS: This is a retrospective observational study, based on demographic, clinical and radiological information of pediatric patients underwent to surgical resection of posterior fossa tumors by a single group between 2011 and 2019. RESULTS: We included 135 patients with a mean age of 7.56 years, mean follow-up of 35.7 months and overall survival of 18.8 months. Considering the histology, most tumors were pilocytic astrocytomas (34.1%), followed by medulloblastomas (27.4%) Total resection was achieved in 77.8% and tumor recurrence was observed in 16.2%. The rate of hydrocephalus was 36.3%, with most shunt procedures performed preoperatively. There was a high rate of complications associated with shunting (42.9%), mostly represented by infection (71.5%). Patients with hydrocephalus were younger (p = 0.001), showing a faster evolution between the onset of symptoms and diagnosis (p = 0.008). Tumor volume (p = 0.1) and location (p = 0.32) were not statistically significant for hydrocephalus, however, the presence of leptomeningeal disease (p = 0.001) was. The resection rate was also significant, with lesions totally resected showing the best results (p = 0.009). Regarding tumor histology, 33.3% of patients with medulloblastoma and 62.5% of patients with ependymoma were shunted. CONCLUSION: One third of children with posterior fossa tumors will require a shunt procedure. Some factors should guide the neurosurgeon during patient counseling and surgical planning to minimize the use of permanent shunts and avoid related complications.
SURG-16. Pediatric oncology neurosurgery, four years after centralization in the Princess Máxima Center
Authors: van Baarsen Kirsten , Slot Mariam , Woerdeman Peter , Han Sen , Hoving Eelco
Published: June 2022

INTRODUCTION: In 2018, the Princess Máxima Center officially opened its doors as a national referral center for pediatric oncology in the Netherlands. This centralization of pediatric oncology also reshaped the pediatric neurosurgery landscape. Almost four years after centralization it is time to make up the balance. METHODS: From the start in May 2018, a predesigned database was kept for all neurosurgical procedures performed in the Princess Máxima Center, Utrecht. Data was collected by a well-trained medical student and under close supervision of a pediatric neurosurgeon. Patient demographic data, tumor data (location, pathology), surgical data (approach, intended and obtained extent of resection), radiology data, and follow up data (complications, functional outcome) were collected. PRELIMINARY RESULTS: From May 2018 to December 2021, 783 oncology related surgeries have been performed in 472 individual patients (56% male; mean age 8 years). There were 316 cranial tumor resections, 279 of which were first resections. Pilocytic astrocytoma was the most frequent diagnosis (38%), followed by medulloblastoma (14%) and ependymoma (11%). Among the more rare tumors there were 29 diffuse midline gliomas and 29 craniopharyngiomas, reflecting the high volume after centralization. The extent of tumor resection and Clavien Dindo complication grading are correlated to time after centralization. CONCLUSION: Four years after the start of centralization, the pediatric oncology neurosurgery service in the Netherlands is well established. Clustering has resulted in high absolute numbers, even for rare tumor types, and growing experience. With this series we hope to create an international benchmark for pediatric oncology neurosurgery.
NURS-03. Effect of psychological intervention on peripherally inserted central catheterization in children with central nervous system tumors
Authors: Zhang Yangqiong , Xiang Yuliang , Zhang Fuqiang , Zhang Xing , Li Juan , Lai Mingyao , Cai Linbo
Published: June 2022

OBJECTIVE: Peripherally inserted central catheterization (PICC) is a frequently used invasive clinical procedure in children with central nervous system (CNS) tumors. How to reduce the psychological impact brought by the operation process and increase the cooperation of children is a concern of medical staff .The study is to investigate the effect of psychological intervention with game strategy on PICC in children with CNS tumors. METHODS: A total of 120 children with CNS tumors who underwent PICC in Guangdong Sanjiu Brain Hospital from January 2019 to February 2021 were enrolled in this study. Patients were divided into two groups according to whether psychological intervention therapy was accepted during PICC, one group was the intervention group and the other group was the control group, with 60 patients in each group. Anxiety was assessed before and after PICC using the FLACC and Spence scores. T test was used to compare the scores of the two groups. RESULTS: Anxiety was found in both groups before PICC, and there was no significant statistical difference between the two groups (p > 0.05). The FLACC score of the two groups during PICC showed that the degree of pain in the intervention group was lower than that in the control group (P < 0.05). After catheterization, the anxiety score of the intervention group was significantly lower than that of the control group (P < 0.05). CONCLUSION: Psychological intervention based on game can reduce the medical fear of children with CNS tumors in the process of PICC and increase the cooperation of children.
NURS-04. Marijuana, Hemp, and the Child with Cancer: Education for Nurses
Authors: Hemenway Molly
Published: June 2022

Many pediatric oncology patients report medical marijuana (MMJ) and hemp-based cannabidiol (CBD) use. Nearly 4,000 minors are registered users of marijuana in Colorado, the first state in the United States of America (USA) to legalize recreational marijuana. Medical marijuana is legalized in 37 states and four territories in the USA. Additionally, due to the bipartisan Farm Bill passed in December of 2018, hemp is federally legal. Forty-three countries have also legalized medical marijuana. With increased legality and many countries decriminalizing marijuana, the use of MMJ and hemp-based CBD is also increasing. This upsurge in use raises significant concerns with pharmacological interactions with CBD and the medications routinely administered to children with cancer (including chemotherapy). Cannabis-derived pharmaceuticals can also have pharmacological interactions. Nurses are the frontline for discussions with patients about MMJ and must be aware of the emerging field of MMJ in pediatric cancer. Education including the difference between tetrahydrocannabinol (THC) and CBD and their indications, extraction methods and safety, product types, infection control, and dosing considerations are important for nurses to learn. Nurses with increased knowledge will then help patients and families make educated and safer choices in treating their children for tumor treatment and side effect management with MMJ and hemp-based CBD. Additionally, nurses can influence patient care protocols and processes for alternative therapy administration enabling an open dialogue between providers, parents, and patients regarding treatments, symptoms, adverse effects, and drug interactions.
OTHR-02. Ways to lower anxiety and influence pain perception by reducing stress hormones and impacting the neurochemicals of patients
Authors: Fernjack Jennifer
Published: June 2022

In this session, you will learn how things in everyday life such as music, laughter, gratitude, acts of kindness and pets can take the edge off a patient’s experience by affecting them physically. The speaker can describe these things first hand by sharing what she experienced through her meningioma brain tumor scare and the corresponding radiation treatments. She can also speak to the benefits of “salient stimulus,” whereby patients who listen to music that is relevant to them during radiation treatments are more apt to be less stressed than other patients because the songs that have meaning can increase dopamine levels. The same can be said for people with dementia who listen to their favorite songs. The balance and stride length of people who have Parkinson’s disease can improve as well when they dance to music that has meaning for them and dopamine levels are influenced along the way. Promoting such things in a hospital setting can benefit the underlying patient and their caregivers, e.g., their families and the people who help them at the hospital. The hospital itself has the potential to benefit too through lower turn over rates with staff and lower sedation rates of patients. Great reminder that even though we can’t control the quantity of life, we can still influence the quality of it, regardless of who you are or where you’re from.
OTHR-04. Single-nucleus transcriptomic atlas of human hindbrain development identifies cellular origins of pediatric brainstem tumors
Authors: Joshi Piyush , Okonechnikov Konstantin , Sepp Mari , Sarropoulos Ioannis , Leiss Kevin , Kutscher Lena M , Kaessmann Henrik , Pfister Stefan M
Published: June 2022

The hindbrain is a key central nervous system structure involved in communication between the brain and the spinal cord, integrating sensory information and coordinating motor responses. Dysregulation in hindbrain development is frequently associated with behavioral disorders and maybe associated tumor formation, stressing the importance of understanding the intricacies of human hindbrain development. Here we performed RNA-sequencing of over 300,000 single nuclei to construct a developing human hindbrain atlas, focusing on pons and medulla, ranging from embryonic to adult stages, profiling the entirety of the hindbrain’s neural and glial populations from progenitors to mature cell types. We describe the transcriptional identity of neuronal cells constituting the pontine and medullary nerve centers including precerebellar, respiratory, auditory and vestibular nuclei; and their differentiation trajectory from the progenitor domains in the embryonic rhombencephalon. To identify the origins of pediatric brain tumors, we mapped ~2,900 bulk and ~50 single-cell transcriptome tumor datasets to the developmental hindbrain atlas, focusing on medulloblastomas, and pediatric low- and high-grade gliomas, and determined cell populations and differentiation states associated with specific tumor groups. We confirmed migrating lower rhombic lip derivatives as the lineage of origin for WNT medulloblastoma. Further, we ascertained early ventral neural progenitor-derived oligodendrocyte lineage as the source of diffuse midline glioma H3K27-altered and postnatal oligodendrocyte progenitors as the origin of pilocytic astrocytoma. In addition, the ependymal lineage originating from glial progenitors was identified as the best match for ependymomas. We show that tumor development has a component that transcriptomically follows its cellular lineage of origin, and identify genes with preserved expression between the respective normal and malignant cell populations. Tumor to normal comparisons also identified tumor-specific genes, providing promising therapeutic candidates. We plan to make our data and analysis pipeline publicly available via user-friendly graphical interface at brain-match.org for unrestricted use of the generated results.
OTHR-18. A pilot study evaluating the access, utilization, and patient satisfaction of basic skin care products among pediatric patients prescribed medications that target the mitogen-activated protein kinase pathway
Authors: Meyer Ashley , Armstrong Amy , Cluster Andrew , Ogle Andrea , Sisk Bryan , Brossier Nicole , Beck Mary , McHugh Michele , Abdelbaki Mohamed , Coughlin Carrie
Published: June 2022

BACKGROUND: The mitogen-activated protein kinase (MAPK) pathway is dysregulated in approximately one third of all malignancies. Agents targeting this pathway are known to cause frequent and significant skin toxicity. METHODS: Patients <21 years of age prescribed any medication targeting the MAPK pathway within the past six months were eligible for this prospective, pilot study. Each participant received a complimentary skin care kit consisting of basic skin and oral care items. At baseline and three months after enrollment, participants completed surveys assessing demographics, skin symptoms, use of the products, and quality of life (QOL; Dermatology Life Quality Index and Child Dermatology Life Quality Index, CDLQI). OBJECTIVES: Primary aims were evaluating utilization of the kit and measuring patient satisfaction of the items included. Secondary aims included determining skin-related QOL and assessing adherence to MAPK targeted therapy. RESULTS: Eleven participants (seven male, four female; median age 13 years, range 4-21 years) have enrolled to date (enrollment goal of 30). Participant therapies included MEK inhibitors (nine), a pan-RAF inhibitor (one), and combination MEK-mTOR inhibition (one). Six have completed the three-month follow-up. Of these six, four rated their satisfaction with the kit as excellent, one each rated very good and fair satisfaction. Five participants rated the kit helpful and thought the kits should be distributed when patients begin therapy. Three started taking their targeted agent before enrolling in the study and their CDLQI changed from 3 to 0.3 (means; improved). Three participants started their targeted agent after enrollment and their CDLQI changed from 1 to 3.3 (means; worsened). CONCLUSIONS: Participants reported that skin care kits were helpful and recommended use by other patients on MAPK-targeted agents. Continued follow-up and enrollment in the study will help further explore the utility of specific products in the kits, as well as changes in patients’ QOL.
OTHR-20. Precision neuro-oncology in the real world. Opportunity and challenges from a UK Oncology Centre
Authors: Apps John , Peet Andrew , English Martin , Adamski Jenny
Published: June 2022

The last five years has shown advances in the molecular classification of brain tumour, molecular profiling techniques and an increased use of targeted therapies. We reviewed the molecular analysis pathways and use of targeted agents at Birmingham Children’s Hospital (BCH), a large (~55 new cases/year) neuro-oncology centre, between 2016-2021. Having previously been analysed locally by limited directed immuno-histochemical stains and referral for specific genetic tests, tissue is now referred for a range of second histopathological opinions and in depth molecular classification, via methylation array, panel sequencing, RNA fusion analysis, and whole genome sequencing. These are accessed through different evolving pathways and consent processes, including referral to other centres, national reference laboratories, clinical studies, and local genetics laboratories with links to national sequencing infrastructures. Different routes result in different reporting structures, timescales and with varying levels of interpretation, often without adequate access to clinical information and context. 21 patients were treated on five targeted agent clinical trials (Afatanib (n=6), Biomede (n=3), eSmart(n=1), PARC (n=7), Vinilo (n=5)), with one patient on both Afatanib and PARC trials. A further two patients visited other centres for trials. Eight patients received MAPK pathway inhibitors through compassionate access pathways, with benefit, including radiological response, in four. Cardiac toxicity was observed in three and retinal oedema in one. Two patients received immune checkpoint inhibition, with rapid fatal enlargement, either progression or pseudo-progression, in one case. These rapid changes in diagnostic and management options offer new opportunities for patients, but bring challenges to the delivery of neuro-oncology services, including the logistics of sample, report, clinical trial, compassionate access management and the increased multi-specialist support required for monitoring and management of toxicities. Integration of targeted agents into the appropriate part of a patient’s treatment strategy requires skilled interpretation of the benefits compared to conventional therapies.
OTHR-21. Ethical reflections via the dilemma method in a pediatric neuro-oncology department
Authors: van Meeteren Antoinette Schouten- , Lenting Simone , Sulkers Mirjam , van de Wetering Marianne
Published: June 2022

BACKGROUND: Professional care for children with a brain tumor can bring considerable ethical questions in clinical practice. These questions can be burdensome and cause distress among professionals, parents and patients. Awareness and skills to bring these aspects into a respectful discussion among colleagues can be meaningful and alleviate the distress. Our objective is to give overview of the ethical case deliberations which took place during a monthly multidisciplinary meeting on the pediatric neuro-oncology department.

METHOD: To describe the type of ethical case deliberations as spontaneously proposed and selected by the team members for discussion. To identify main values in the care process for professionals via the dilemma method in monthly meetings led by a trained facilitator.

RESULTS: The monthly meetings were visited regularly by 9-14 diverse professionals (median 10) of the team: nurses, oncologists, social worker, psychologist, educational specialist. The selected moral questions concerned children with a brain tumor between 4-13 year old (median 9) with following ten subjects: 3 not sharing the infaust prognosis with a child, 2 avoiding medical care in follow up /treatment, 2 cultural different approach for food and drink intake, 2 crossing professional boundaries and 1 time worries about emotional safety of a child. The main values that were recognized to play crucial role in the care process were honesty, respect, autonomy, quality of life, health, tolerance, courage and safety. The participants felt supported in their professional skills by sharing reflections on personal moral considerations and by openly discussing different views and experiences of other participants.

CONCLUSION: The monthly ethical case discussions disclose high lights in the burden of professional care in pediatric neuro-oncology. These meetings about moral questions are supportive in the competence of the professionals to recognize and communicate about these important dilemmas.
OTHR-24. Impact of physical activity on postural stability and coordination in children with posterior fossa tumor: randomized control phase III trial
Authors: Usama Mahmoud , Abdelaziem Faten H , Rashed Wafaa M , Maher Eslam , El Beltagy Mohamed , Zekri Wael
Published: June 2022

BACKGROUND: Posterior fossa tumor is a type of brain tumor that is located at the borders of both the brain stem and cerebellum. The cerebellum is the brain region in charge of balance and coordination. Pediatric patients diagnosed with posterior fossa tumor have been reported to fall frequently. OBJECTIVES: The aim of this study is to investigate the effectiveness of balance and coordination training in these children. METHODS: This randomized control clinical trial was carried out between September 2020 and April 2021 at Children’s Cancer Hospital-57357. The inclusion criteria of the participants were - patients with posterior fossa tumor in maintenance phase and, age between 5-12 years. The study participants were randomly assigned into three groups: Group I/Control group: they received Pilates core stability exercises program, Group II/Balance group: They received the same program plus HUMAC balance program, and Group III/Coordination group: They received the same program plus coordination exercises of BOT-2. Descriptive statistics for patients’ characteristics were reported as medians and interquartile ranges for quantitative variables, frequencies, and percentages for qualitative ones. Significance level of P value was at <0.05. RESULTS: Sixty children including 38 boys and 22 girls were enrolled in this study. In all three groups, postural stability and coordination improved significantly in terms of modified clinical test of sensory integration of balance, center of pressure, limits of stability, bilateral coordination, and upper-limb coordination.CONCLUSION: The current study supports the value of adding postural stability and coordination training to the physiotherapy plan for children with posterior fossa tumor. Clinical trial information: RCT no#NCT04528316.

Keywords: Posterior fossa tumor, Children, HUMAC, BOT-2, Postural stability, Balance, Coordination.
OTHR-28. Multi-institution analysis of tumor mutational burden and outcomes in pediatric CNS tumor patients
Authors: Parisi Rose , Patel Roshal , Rood Gavrielle , Bowden Acacia , Turco George , Korones David , Andolina Jeffrey , Comito Melanie , Barth Matthew , Weintraub Lauren
Published: June 2022

Pediatric CNS tumors are the leading cause of pediatric cancer mortality. Research addressing genomic biomarkers and clinical outcomes is needed to inform therapeutic decision making. Tumor mutational burden (TMB) has been correlated with decreased survival across cancer types. This study is the first to examine TMB and outcomes in pediatric CNS tumor patients across multiple academic medical centers. We conducted a retrospective analysis of 121 pediatric patients (61 female (50%)) with a median age of 9 diagnosed with a primary CNS tumor at Albany Medical Center, Roswell Park Comprehensive Cancer Center, Upstate University Hospital, or University of Rochester Medical Center from 2008 to 2021. Common tumor types included low-grade glioma (N=51), high-grade glioma (N=30), medulloblastoma (N=11), ependymoma (N=7), ganglioglioma (N=4), and 18 other CNS tumors. Seventy-one patients had driver-mutations, including TP53 inactivation (n=17), BRAF-KIAA1549 fusion (n=16), FGFR1 amplification (n=12), BRAF V600E mutation (n=12), NF1 loss (n=12), and H3F3A K28M mutation (n=6). TMB data was available for most patients (N=91), median TMB was 1 mutations/megabase (mut/Mb, range=0-132). There were 26 deaths observed; patients with high TMB (≥3 mut/Mb; N=35) as compared to patients with low TMB (<3 mut/Mb; N=56) were more likely to have a death event, 43% (N=15) vs 9% (N=5), respectively. High TMB tumors were more frequently high-grade (77%) than low-grade (41%). High TMB tumors were more frequently treated with systemic therapy (86%) compared to low TMB tumors (70%). Tumor progression was more common in high TMB (71%) than in low TMB tumors (54%). This multi-institutional analysis suggests that high TMB is correlated with higher rates of progression and death as compared to low TMB tumors. Knowledge of these findings is critical for identifying patients who may benefit from alternative treatments, such as immunotherapies.
OTHR-29. Exploring delays in diagnosis for children with brain and spinal cord tumors: a neuro-oncologist, epidemiologist and national nonprofit establish a consortium to discover the nature and extent of the problem in the United States
Authors: Riley Kathy , Coven Scott , Cullen Jennifer
Published: June 2022

Childhood brain and spinal cord tumors are the second most common pediatric cancer and the leading cause of disease-related mortality among children between one and nineteen years of age (Johnson & Cullen, 2014). To date, literature fails to acknowledge the perceived delay in diagnosis from a caregivers’ and providers’ perspective as it relates to disparities of care for a child with a brain or spinal cord tumor. Delay in diagnosis is a term used widely to define the time interval from onset of symptoms to confirmed diagnosis (Mullen, Barr & Franco, 2021). Our experience in caring for children with CNS tumors has demonstrated a disconnect in perception of delay in diagnosis between caregivers and providers. Furthermore, to our knowledge, there is no standardized data collection tool to assess delays in diagnosis and to enable the exploration of their relationship to the patient journey from time of diagnosis through long-term outcomes of patients with brain and spinal cord tumors. Timing of diagnosis of a brain or spinal cord tumor in a pediatric patient may be a predictor of clinical outcomes (Wilne, Dineen, Dommett, Chu & Walker, 2013). Additionally, the length of time from symptom onset to diagnosis may exacerbate caregiver distress which, in turn, impacts clinical outcomes. Associated social determinants of health, perceptions of credibility (e.g., not being believed about symptoms), and negative interactions with health care providers may contribute to inequalities of healthcare related to delays in diagnosis. This presentation will explore themes and key factors contributing to delays in pediatric brain and spinal cord tumor diagnoses developed through the work of our consortium. The goal of our work is to develop metrics and survey items that will be used to quantify sources of delays to improve our understanding and promote greater timeliness in diagnoses (Scott, Walter, Webster, Sutton, &Emery, 2013).
OTHR-30. Multidisciplinary approach to childhood cancer bio-banking improves enrollment and enables better access to diagnostic and therapeutic studies
Authors: Zhukova Nataliya , Habarakada Dilru , Drinkwater Caroline , Danks Andrew , Xenos Chris , Kumar Beena , Haddad Lauren , Wood Paul , Cain Jason , Firestein Ron , Downie Peter
Published: June 2022

Despite the significant progress made in the multi-modal treatment of childhood malignancies over the last four decades with a concomitantly increased cure rates, the benefit is still largely limited to patients with leukemias, lymphomas and localized non-CNS solid tumors, leaving patients with high-risk non-CNS solid tumours and most CNS malignancies with minimal advancements. More research is critical to understand what drives these cancers and to investigate the best ways to deliver curative therapies. Translational research relies on patient-derived tissue samples, animal models and cell-cultures to understand the biological, genetic, and molecular mechanisms of disease. To facilitate patient care and outcomes, it is becoming increasingly important that paediatric clinical trials include tissue availability as part of eligibility criteria, making collection and storage of patient tissue a mandate of personalised medicine and a pillar of modern paediatric cancer medicine. Monash Children’s Cancer Biobank was established in 2011. Since 2017, a total of 64 patients were diagnosed with CNS malignancies across all grades, with an overall 69% of patients’ tissues being biobanked at the time of initial diagnosis. A co-ordinated, multidisciplinary approach to biobanking is crucial to the success of tissue acquisition. Through the combination of an educational forum, regular neuro-surgical multi-disciplinary meetings, and the early involvement of medical oncology and biobank staff, with our neurosurgical and clinical pathology colleagues, as part of patient management planning, the tissue acquisition for biobanking increased from 44% to 82% over the course of 5 years. This consequently led to a 100% enrolment to tissue-enabling studies, significantly improving identification of targetable molecular lesions, enrolment onto treatment clinical trials and identification of patients with cancer predisposition syndromes.
OTHR-39. Extraneural spreading of a diffuse leptomeningeal glioneuronal tumor in a child: patient-derived models show sensitivity to vinblastin and trametinib
Authors: Messiaen Julie , Claeys Annelies , Shetty Aniket , Spans Lien , Derweduwe Marleen , Uyttebroeck Anne , Depreitere Bart , Bempt Isabelle Vanden , Sciot Raf , Ligon Keith , Jones David , Jacobs Sandra , De Smet Frederik
Published: June 2022

Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare neoplasms of the central nervous system. We describe the generation of patient-derived models from a DLGNT that metastasized to the peritoneal cavity via a ventriculoperitoneal shunt in a child. The original tumor contained a KIAA1549:BRAF fusion with a chromosome 1p deletion and corresponded with methylation subclass DLGNT-MC-2 From a sample of ascitic fluid, metastatic tumoral cells could be extracted and expanded ex vivo into a long-term cell culture model. This patient-derived cell line (PDCL) showed mixed morphological phenotypes and expressed MAP2 and SYP. The KIAA1549:BRAF fusion was preserved and the PDCL still corresponded to the original methylation subclass DLGNT-MC-2. Whole-genome sequencing showed additional mutations potentially contributing to the malignant behavior of the tumor. Cytotoxic assays performed on the PDCL indicated high sensitivity to vinblastine and trametinib (MEK-inhibitor) and intermediate sensitivity to DRD/ClpP-modulators. The PDCL underwent viral transduction to induce GFP-fLux positivity and was intraperitoneally injected into immunocompromised mice. A mouse model could be generated, with the growth of a peritoneal tumor in a localized manner. The cells grown from the mouse tumor were again put into culture and were afterwards subjected to the same treatments as the PDCL. This confirmed a similar profile, with high sensitivity to vinblastin and trametinib and an intermediate sensitivity to the DRD/ClpP-modulators. In conclusion, we were able to generate patient-derived models from a metastatic DLGNT, which recapitulate the molecular characteristics of the original tumor. The models showed high sensitivity to vinblastin and targeted therapy with MEK-inhibition, but further studies are necessary to define the adequate treatment for this kind of tumor.
OTHR-45. Kids First Variant WorkBench: application to germline genomic discoveries in the Children's Brain Tumor Network
Authors: Guo Yiran , Costanza Jeremy , Botek Christophe , Brown Miguel , Higgins David , Zhu Yuankun , Farrow Bailey , Heath Allison , Resnick Adam , Ferretti Vincent
Published: June 2022

The Gabriella Miller Kids First Pediatric Research Program (Kids First) aims at facilitating researchers to uncover new insights into the biology of childhood cancer (CC) and structural birth defects (SBD). Kids First has two initiatives, i) whole genome sequencing of biospecimens from families with CC/SBD, and ii) establishing Kids First Data Resources. Kids First Data Resource Center developed the Kids First Data Resource Portal (KFDRP), a centralized platform to search, view, analyze, and identify currently accessible data from both Kids First and collaborative cohorts, incorporating omics and phenotypic information of 30 studies and 26,300 participants. A recently released KFDRP component is Variant WorkBench (VWB), enabling users to query, mangle, analyze and visualize genomic variants from participating cohorts, with the Children’s Brain Tumor Network (CBTN) being one of the cohorts. VWB supports programming languages such as Python, Spark, SQL and R for in-depth analysis in Apache Zeppelin notebooks. In addition to variant calls and phenotypic information, VWB hosts rich external variant annotations in the public domain, such as Cancer Hotspots, COSMIC and ClinVar. Users can also load additional databases (e.g. Human Gene Mutation Database/HGMD) within a notebook, import custom datasets as temporary query tables, export analysis outputs to local drives, visualize analysis results in multiple chart styles, display local figures, and save notebooks for sharing, further use and Cavatica projects. In an effort to screen tier 1 genes (n=578) from the most recent Cancer Gene Census provided by COSMIC in CBTN, we identified ~127,500 germline variants that are both rare and damaging, or that are already cataloged in the most recent version of ClinVar/HGMD. The whole process took less than one hour which is much faster than conventional methods. VWB enables efficient genomic variant analysis and discoveries in pediatric neuro-oncology research with advanced big data technology.
PATH-02. Using DNA methylation profiling to define tumor type and appropriate treatment: a case report and review of the literature of a rare CNS CIC altered sarcoma
Authors: Brodwater William , Wilson Yelena , Judd Alexis , Rush Sarah , Wright Erin
Published: June 2022

The utilization of methylation profiling is increasingly becoming part of the standard evaluation for high-grade malignancies. CNS primary tumors with CIC alteration are a recently recognized CNS tumor entity identified via DNA methylation profiling of primitive neuroectodermal tumors (PNET). PNETs have historically carried a poor overall prognosis; however, CNS tumors with CIC alteration have rarely been described in the literature and much remains to be discovered regarding the presentation, tumor characteristics, outcomes, and ideal treatment strategy to optimize survival in these patients. We describe the case of a 2-year-old Hispanic female with a CNS primary tumor with CIC alteration. This patient initially presented with a five-week history of fatigue, headaches, emesis, and right-sided muscle weakness and was found to have a right-sided supratentorial mixed solid and cystic mass. The initial diagnosis was consistent with a high-grade neuro-epithelial tumor based on histology and standard CNS tumor genetic markers. Due to poorly defined tumor characteristics, a sample was also sent for DNA methylation profiling. The profiling pattern was consistent with a CNS CIC altered sarcoma thereby significantly altering the treatment plan. Accurate diagnosis is critical in managing patients with cancer. DNA methylation profiling has contributed to diagnostic accuracy in these aggressive tumors; however, it also creates challenges with beginning treatment expediently due to the time required for processing and interpretation. This case illustrates the positive utility of DNA methylation to better characterize tumor types and the impact this has on both treatment as well as prognosis.
PATH-03. Clinically Tractable Outcome Prediction of Group 3/4 Medulloblastoma Based on TPD52 Immunohistochemistry: a Multicohort Study
Authors: Delaidelli Alberto , Dunham Christopher , Santi Mariarita , Negri Gian Luca , Triscott Joanna , Zheludkova Olga , Golanov Andrey , Ryzhova Marina , Okonechnikov Konstantin , Schrimpf Daniel , Stichel Damian , Ellison David , von Deimling Andreas , Kool Marcel , Pfister Stefan , Ramaswamy Vijay , Taylor Michael , Korshunov Andrey , Sorensen Poul
Published: June 2022

BACKGROUND: International consensus and the 2021 WHO classification recognize eight molecular subgroups among Group 3/4 medulloblastoma (representing ~60% of medulloblastoma). However, very few clinical centers worldwide possess the technical capabilities to determine DNA-methylation patterns or other molecular parameters of high-risk for Group 3/4 tumors. As a result, biomarker-driven risk stratification and therapy assignment constitutes a major challenge in medulloblastoma research. Here, we identify an immunohistochemistry (IHC) marker as a clinically tractable method for improved medulloblastoma risk-stratification. PATIENTS and METHODS: We bioinformatically analyzed published medulloblastoma transcriptomes and proteomes identifying as a potential biomarker TPD52, whose IHC prognostic value was validated across three Group 3/4 medulloblastoma clinical cohorts (n = 387) treated with conventional therapies. Risk stratification and prediction capability were computed utilizing uni- and multivariate survival analysis. Newly developed risk classifiers including TPD52 IHC were compared to state-of-the-art risk stratification schemes in terms of prediction error, area under the time-dependent receiver operating characteristic (ROC) curves and C-statistic. RESULTS: TPD52 IHC percentage positivity represents a significant independent predictor of early relapse and death for Group 3/4 medulloblastoma (HRs between 3.67-26.7 [95% CIs between 1.00-706.23], p = 0.05, 0.017 and 0.0058). Cross-validated survival models incorporating TPD52 IHC with clinical and molecular features (subgroup affiliation, MYC status) outperformed existing disease risk-stratification schemes, and reclassified ~50% of patients into more appropriate risk categories. Finally, interaction effect in multivariate analyses revealed that TPD52 immunopositivity could be a predictive indicator of poor response to chemotherapy (HR 12.66 [95% CI 3.53-45.40], p < 0.0001), suggesting important implication for therapeutic choices. CONCLUSION: The current study adds an important asset to improve risk-stratification for Group 3/4 medulloblastoma. Integration of TPD52 IHC in classification algorithms significantly improves outcome prediction and can be rapidly adopted for risk stratification on a global scale, independently of advanced but technically challenging molecular profiling techniques.
PATH-07. Diagnostic and therapeutic value of cerebrospinal fluid biopsy in pediatric brain tumors
Authors: Li Shaoqun , Lai Mingyao , Cai Linbo
Published: June 2022

BACKGROUND: The application of cerebrospinal fluid (CSF) biopsy in brain tumors is valuable. This paper further explores the diagnostic and therapeutic value of CSF biopsy in pediatric brain tumors. METHODS: In this study, children with primary brain tumor aged ≤18 years old in Guangdong Sanjiu Brain Hospital were enrolled．CSF next-generation sequencing (NGS) tests were required for all included patients. The genetic mutations in these children were analyzed. RESULTS: A total of 12 pediatric brain tumors who underwent CSF NGS were included in this study. 9 patients were brainstem glioma and 3 were pilocytic astrocytoma. The mutated genes were detected in 67% (8/12) patients by CSF NGS. In brainstem glioma, the rate was 67% (6/9), and the most common genes were H3F3A (5/6, 83%) and TP53 (5/6, 83%). Other detected genes included EGFR, CDK4 and NF2. H3F3A mutation is of great significance for the diagnosis and treatment of brainstem glioma, and CDK4 and EGFR are valuable for the treatment. In pilocytic astrocytoma, the deteaction rate was 67% (2/3), and the genes included KIAA1549-BRAF fusion, FGFR1 and PTPN11 mutations. KIAA1549-BRAF fusion is of great value in the diagnosis and treatment of pilocytic astrocytoma, and FGFR is valuable in the treatment. CONCLUSIONS: Fluid biopsy of CSF for pediatric brain tumors may be an important supplement to histological diagnosis, especially when histopathology is not available. The results are significant for the diagnosis and treatment of pediatric brain tumors.
PATH-12. A new powerful tool to simultaneously deliver DNA methylation profile and driver fusions detection based on Nanopore Sequencing
Authors: Filser Mathilde , Hamza Abderaouf , Girard Elodie , Servant Nicolas , Renault Victor , Merchadou Kevin , Bourneix Christine , Varlet Pascale , Uro-Coste Emmanuelle , Tauziède-Espariat Arnault , Doz Francois , Bourdeaut Franck , Delattre Olivier , Masliah-Planchon Julien
Published: June 2022

The fast advances in molecular biology have led to the discovery of new genetic and epigenetic driver events that play a key role in the pathogenesis of central nervous system (CNS) tumors. These data showed the importance of molecular biology, and in particular methylation profiling and fusion detection, to complete the histological examination. Exploring all these complex genomic and epigenomic alterations with the technologies implemented in the routine diagnosis requires massive laboratory equipment. In addition, it could take weeks before getting data that could be important to adapt the diagnosis, prognosis, and to ultimately guide the treatment’s choice. We describe the innovative potential of a nanopore sequencing device to obtain fast and multiple information to characterize CNS tumors. Adaptive-sampling is a software-controlled enrichment unique method that allows simultaneous methylation profiling, copy number landscape assessment, and fusion gene detection. Thereby, this technology brings comprehensive molecular information that could be very important for CNS tumor classification in a very short delay (below one week) and with a relative low cost compared to the combined other molecular analysis needed to get the same information. We report ten cases of diverse CNS tumors with already known oncogenic structural variants such as YAP1-MAMLD1 fused ependymoma, CNS neuroblastoma with FOXR2 activation, CNS high-grade neuroepithelial tumor with BCOR and MEN1 alteration, and atypical teratoid rhabdoid tumors (ATRT). For these tumors, using adaptive sampling with the nanopore sequencing, we were able to detect fusion genes as driver events, while obtaining at the same time the methylation profile to corroborate the tumor classification. Our results with this combined approach, never described before, demonstrate its feasibility as a new extremely powerful tool and show remarkable perspectives for this technology to bring a fast and comprehensive tumor molecular characterization.
LINC-03. A single center retrospective analysis of current therapy and outcome of central nervous system tumors in children of Beijing
Authors: Li Miao , Du Shuxu , Sun Yanling , Gong Xiaojun , Liu Jingjing , Ren Siqi , Zhang Jin , Gao Wenchao , Li Shuting , Wan Lulu , Wang Yuan , Wu Yuefang , Liu Yan , Zhang Zhen , Tang Hong , Wu Wanshui , Sun Liming
Published: June 2022

OBJECTIVE: To explore the clinical characteristics, therapy and outcome in children with central nervous system (CNS) tumors in Beijing, China. METHODS: Clinical data of 1003 patients with newly diagnosed CNS tumors under the age of 15 years admitted to Beijing Shijitan Hospital between January 2017 and December 2021 were retrospectively analyzed. The diagnoses were confirmed by pathology and/or molecular tests. RESULTS: 34 patients were lost to follow up. Medulloblastoma (n=472), ependymoma (n=79), ETMR (n=59) and pinealoblastoma (n=19) were treated according to HIT-2000/2017, 5-year progression-free survival (PFS) and overall survival (OS) were 76.4 ± 2.3%/ 84.8 ±1.9% in MB, 88.8±3.7% /89.5±3.8% in ependymoma, 49.9±7.6%/59.6±10.7% in ETMR, and 3y-PFS/OS of 11.1±10.5%, 90.0±9.5% in pinealoblastoma. The detailed histology of 59 cases of embryonal tumors included 40 cases of CNS embryonal tumor, 9 neuroblastoma, 7 ETMR, and 3 rare tumors (Intracranial mesenchymal tumor with FET-CREB fusion, CNS high-grade neuroepithelial tumor with BCOR alteration, and Melanotic neuroectodermal tumor of infancy). Among 19 cases of pinealoblastoma, two contain DICER1 mutations. Atypical teratoid/rhabdoid tumors (n=36) were treated by EU-RHAB-Protocol with 3y-PFS/OS of 42.2 ± 9.4 % and 62.8 ± 9.5 %. For low-grade gliomas (n=153, 114 cases of OPG and 39 other non-STR/NTR or progressive cases) under SIOP-LGG 2004, 5y-PFS/OS rates were 77.6±5.2% and 92.4±3.2%; Comparatively, among 63 cases of high-grade gliomas, 19 cases survived with median survival of 52 months, 44 cases died. Choroid plexus cancers (n=13) were treated according to CPT-SIOP-2009 with 5y-PFS /OS of 68.4 ± 13.1 % and 64.8±14.3 %. Among 109 germ cell tumors, 5y-PFS/OS were 93.8±2.8% and 95.5±2.2%, respectively. CONCLUSION: The prognosis of CNS tumors are related to pathology, molecular type and individualized therapy. By international multicenter cooperation and adopting advanced protocols, the survival rates of pediatric CNS tumors can be significantly improved.