bluuebunny/crossref_metadata_2025 huggingface dataset:
QOL-12. LESSONS LEARNED FROM LONGITUDINAL CARE IN POSTERIOR FOSSA SYNDROME
Authors: Tsetlina Vera , Cassidy Deborah , Tenaglia Amy Lynn , Levin Jared , Tsao Elaine , Ibanez Katarzyna
Published: June 2024

BACKGROUND

Posterior fossa syndrome (PFS) is a constellation of neurobehavioral symptoms occurring in 8–24% of children following surgical resection of posterior fossa tumors. Symptoms may include a combination of mutism or reduced verbal output, emotional lability, hypotonia, dysphagia, ataxia and weakness. Direct surgical injury to the dentato-thalamo-cortical pathway has been the proposed pathological mechanism. The trajectory of recovery and the functional outcomes of PFS are not well described. Khan et al. published a prospective study on children after medulloblastoma resection where they divided PFS into type 1 (complete mutism) and type 2 (diminished speech). They showed that PFS type 1 patients had a worse prognosis and a delayed recovery with 44.4% of children being non-ambulatory at one year. Ricci et al. recently published a more detailed severity grading algorithm which over time will hopefully help with data collection and analysis leading to improved prognostication regarding functional recovery.

METHODS

We present a unique longitudinal look (range 12 months to 19 years) at 5 pediatric patients with posterior fossa tumors who developed PFS following their tumor resections.

RESULTS

Tumor diagnoses included ependymoma and medulloblastoma. Rehabilitation interventions consisted of acute inpatient rehabilitation where they received intensive physical, occupational, speech and feeding therapy. Most patients benefited from early utilization of trunk and lower extremity bracing as well as a variety of assistive devices and durable medical equipment. Patients continued their rehabilitation for months to years in an outpatient and school setting. All patients demonstrated significant neurological and functional gains however, none of them had a complete resolution of symptoms. We discuss the anatomy, the time to symptom onset, the trajectory of our patients’ recoveries and the rationale behind the applied rehabilitation strategies.

CONCLUSIONS

This work gives insights on long term sequalae of PFS and demonstrates current rehabilitation approach for children with this complex condition.
QOL-13. RETURNING TO SCHOOL TO REDUCE LATE COGNITIVE SIDE EFFECTS IN SURVIVING CHILDREN WITH BRAIN TUMORS AFTER RADIOTHERAPY
Authors: Zhang Yangqiong , Yang Huajun , Xiang Yuliang , Wang Danlei , He Lihan , Cai Linbo
Published: June 2024

OBJECTIVE

To investigate whether returning to school can reduce advanced cognitive impairment related to chemo-radiotherapy in children with brain tumors.

METHOD

From 2013 to 2018, 132 children with brain tumors aged 3-14 who received chemo-radiotherapy for brain tumors were retrospectively analyzed for gender, tumor type, age of radiotherapy, education level, place of residence, and return to school. The Wechsler Intelligence Test was conducted before and 5-10 years after radiotherapy and chemotherapy, and they were divided into a return to school regular class group, a return to school family/community education group, and a non return to school no education group.

RESULT

78 cases were in the group of returning to school for regular classes, 30 cases were in the group of returning to school for family/community education, and 24 cases were in the group of not returning to school without teaching. The verbal intelligence, operational intelligence, and overall intelligence of the group returning to school and attending regular classes were significantly higher than the other two groups. The return to school situation of urban children is better than that of rural children (p=0.028<0.05). Children with germ cell tumors had the best return to school, while those with glioma had the worst return to school (p<0.05). The quality of life score of returning to school children was significantly higher than that of out of school children (p<0.05).

CONCLUSION

Children returning to school are significantly better than those of out of school children in terms of physiological, emotional, social, and school functions. After 5 years of radiotherapy, the cognitive level of the returning children significantly improved, and the overall quality of life was relatively high.
QOL-16. IMPACT OF LESION LOCATION ON MOTOR AND COGNITIVE OUTCOMES IN PEDIATRIC CEREBELLAR TUMORS
Authors: Walsh Karin , Stoodley Catherine , Nielsen Johanna , Kaufman Alex , Baucom Brooks , Muir Aly , Pakhejad Maneli , Tegiacchi Rebecca
Published: June 2024

BACKGROUND

Children with cerebellar damage are at increased risk for various adverse outcomes, including higher rates of autism and long term neurocognitive challenges. Traditionally considered a motor structure, extensive evidence links the cerebellum to a range of behaviors and atypical cerebellar structure and function have been reported in multiple neurodevelopmental and psychiatric conditions. A key feature of cerebellar neuroanatomy are the functional subregions that support sensorimotor and non-motor functions, leading to the hypothesis that motor, cognitive and behavioral outcomes should be predicted by the cerebellar lesion location.We aimed to determine how lesion location relates to outcomes in pediatric cerebellar patients. We predicted that lesions of the anterior lobe would disrupt motor performance, posterolateral lesions would impact cognitive functions, and behavioral dysregulation would be associated with posterior midline damage.

METHODS

We conducted lesion-symptom mapping in 30 children with a history of cerebellar tumor resection (sex: 19 male, 11 female; age at diagnosis, mean 6.8 years [SD 4.2]). Clinical MRI scans and neuropsychological data were used to evaluate the impact of lesion location on motor (pegboard), cognitive (verbal comprehension, verbal fluency, working memory, processing speed) and behavioral control measures (BRIEF). We mapped individual lesions using T1-weighted MRIs and normalized the lesion maps into standard template space for group analyses.

RESULTS

Behavioral scores ranged from impaired to above average. Lesion overlap maps were used to assess the lesion patterns associated with performance. As predicted, anterior and medial lesions disrupted motor performance and processing speed; posterolateral lesions were associated with impaired cognitive scores.

CONCLUSIONS

These preliminary analyses indicate that long-term outcomes are associated with disruption of specific cerebellar subregions. This could aid in prognosis and management of pediatric cerebellar tumor patients. Future work will address age of surgery, longitudinal changes in performance, and the developmental impact of early cerebellar disruption on supratentorial structures.
QOL-23. POTENTIAL MYELIN REPAIR AFTER IRRADIATED PEDIATRIC BRAIN TUMOR: A MAGNETIZATION TRANSFER IMAGING ANALYSIS
Authors: Baudou Eloïse , Tseng Julie , Ryan Jennifer L , Bouffet Eric , Bartels Ute , Timmons Brian , de Medeiros Cynthia , Mabbott Donald J
Published: June 2024

BACKGROUND

Exercise training and metformin treatment may improve cognition after cranial irradiation in pediatric brain tumors (PBT), but the neuronal mechanisms underlying the effect of these interventions remains unknown. Magnetization transfer imaging (MTI) is an imaging technique that may be sensitive to white matter microstructure – including myelin.

METHODS

In this work, we analyzed changes in magnetization transfer ratio (MTR) over a 12-week period in irradiated PBT survivors who participated in pilot clinical trials entailing 12 weeks of exercise training (exercise group, n=17), or metformin treatment (n=12). Pre- and post-intervention assessment included MRI scanning and neurocognitive tests. A no intervention control group, (n=7) was also included and seen before and after a 12 week period of time. We used a longitudinal Tract-Based Spatial Statistics (TBSS) approach to analyze differences in MTR across the 12 weeks in the three groups, using as covariates: age at baseline, sex, handedness, age at diagnosis and delay from diagnosis. Then we performed correlations between mean MTR changes and behavioral outcomes.

RESULTS

Clusters of significant increase in MTR were observed in the right temporal lobe in the exercise group after intervention and in the right minor forceps in the metformin group after treatment. These changes respectively correlated with higher performance in free recall score in exercise group and with higher performances in inhibitory control and attention in metformin group. There was no difference in MTR changes between groups nor within the control group.

DISCUSSION

This exploratory work suggests either a 12-week period of exercise training or metformin may promote myelination in PBT survivors in brain regions. These changes appear to be associated with improved memory and executive function, two core domains of neurocognitive deficit in this population.
QOL-35. ANALYSIS ON THE EVOLUTIONARY PATTERN OF COGNITIVE FUNCTIONS IN CHILDREN ON FOLLOW-UP FOR BRAIN TUMORS
Authors: Liguoro Ilaria , Toniutti Maristella , Tuniz Francesco , Vindigni Marco , Pegolo Enrico , D’Agostini Serena , De Colle Maria Cristina , Mascarin Maurizio , Coassin Elisa , Cogo Paola Elisa , Pilotto Chiara , Zilli Tiziana
Published: June 2024

BACKGROUND

Long-term cognitive sequelae of paediatric brain tumors are of increasing interest. The role of histology and surgery remains still unclear. Our study aimed to evaluate children cognitive functioning before and after brain tumors surgery, and at the end of additional treatments.

METHODS

New diagnoses of paediatric primary brain tumors were prospectively assessed. Neurocognitive evaluations were performed at diagnosis (T0), within 7-10 days from surgery (T1) and 12-18 months after the end of treatments (T2). Language, learning and memory, attention, executive functions, visuo-constructional and sensorimotor skills were evaluated at T0 and T1, Intelligent Quotient (IQ) was explored at T0 and T2.

RESULTS

Twenty-five patients (M:F=15:10, mean age 10.9±3.4 years) were enrolled between January 2019 and December 2022. In comparison to normal values (>7.0), at baseline patients showed major deficits in narrative memory (6.6±3.7, p<0.001) and visuo-spatial memory (copy design tasks: general 6.8±3.9, p<0.001, specific 6.2±3.3, p<0.001, motor 5.2±3.2, p<0.001). At T1 assessment, significant deficits remained in narrative memory (6.2±3.3, p<0.001) and visual-motor coordination (copy design tasks: specific 5.9±3.0, p<0.001 and motor 4.8±4.3 p<0.001); attention and visual-constructional abilities significantly improved (p=0.04 and p=0.001). On the visual construction test, children with high-grade histology scored lower than the low-grade group (Rey- Osterrieth complex figure-copy 5.1±4.4 vs 11.0±4.3; p=0.019). At T2 evaluation children showed persistent deficits in visuo-spatial processing and a possible decline in IQ scores, with lower scores compared with T0 (93 vs 100, p=0.05).

CONCLUSIONS

Children with brain tumors may present several neuropsychological impairments at diagnosis, particularly those with high-grade diseases. Surgery may have a positive effect on the recovery of some cognitive functions. However, cognitive decline may worsen over time. Baseline and periodic neurocognitive evaluations should be encouraged to identify functional difficulties and to develop a tailored treatment approach for the patient.
QOL-40. FAMILY MENTAL HEALTH SCREENING EARLY AFTER A DIAGNOSIS OF PEDIATRIC BRAIN TUMOR
Authors: Rodemann Ashley , Hartman Mary E , Abdelbaki Mohamed , Cluster Andrew S
Published: June 2024

INTRODUCTION

A new diagnosis of a brain tumor in a child has significant emotional consequences for every member of the family. Despite this, early phases of oncologic care rarely provide formal mental health screening.

METHODS

In 2021, we implemented a mental health screening protocol for patients with a newly diagnosed brain tumor admitted to our pediatric intensive care unit (PICU) at the time of diagnosis, and their parents. Screening instruments were selected based on previous validation and relevance to both a brain tumor diagnosis and PICU admission. Parents were contacted by our team shortly after their child’s diagnosis and completed the screening within a month via an online interface. Parent proxy reports for children were used when necessary. Scores were shared with the family and neuro-oncology team. When indicated, supportive counseling and care coordination were offered.

RESULTS

Since 2021, 97 new brain tumor patients have met criteria for mental health screening. Of these, 72 patient and parent dyads were provided the screening protocol, and 31 fully completed the screening (mean patient age 7.3 yrs; 81% white; 58% male). Of the families that completed the evaluation, most parents (83%) reported their child’s diagnosis negatively impacted their health-related quality of life (HRQL), while 75% of children themselves reported a lower HRQL than population norms. Nearly half of children (44%) self-reported having symptoms outside of normal range for anger, anxiety or depression and 33% had abnormal scores for pain interference with their daily lives. More than half (65%) of families reported lower family functioning than population norms.

CONCLUSION

Families of children with a new diagnosis of brain tumor are at risk for impaired mental health and quality of life early after diagnosis. A systematic approach to assess and address these concerns early after diagnosis is needed.
QOL-46. EFFECTIVENESS OF A TELEREHABILITATION PROGRAM TO IMPROVE VISUAL PERCEPTION IN CHILDREN AND ADOLESCENTS WITH HEMIANOPIA CONSECUTIVE TO A BRAIN TUMOUR
Authors: Bajin Inci Yaman , Misawa Mariana , Zhang Bill , Daibert-Nido Monica , Tchao Danielle , Garcia-Giler Eduardo , Cheung Kyle , Appel Lora , Nasir Pi , Reginald Arun , Tabori Uri , Bartels Ute , Ramaswamy Vijay , Markowitz Samuel N , Bouffet Eric , Reber Michael
Published: June 2024

BACKGROUND

Brain tumours in children often lead to visual impairment, which presents as a significant morbidity for long-term survivors. A recent Children Cancer Survivor Study showed that 22.5% of the patients with astroglial tumours had visual impairment five years after the diagnosis. In the pediatric population with hemianopia, there are no standardized protocols for managing vision loss. This study evaluated a 6-week home-based telerehabilitation program (home-based 3D-MOT-IVR) on visual perception in children with hemianopia consecutive to a brain tumour.

METHODS

This phase 2a, open-labelled, non-randomized, single-arm study included ten patients aged 12-18 years old with hemianopia consecutive to a pediatric brain tumour. Patients followed a 6-week home-based 3D-MOT-IVR with remote control of the device from the UHN laboratory. Visual assessments were performed at baseline, 2, 4, and 6 weeks, with follow-ups at 1 and 6 months to check the visual field, contrast sensitivity and reading speed.

RESULTS

The home-based 3D-MOT-IVR intervention proved feasible and safe, with no reported adverse events. All participants completed the prescribed stimulations, pre- and post-intervention assessment points, and 90% completed the follow-ups. Remarkably, the outcomes revealed significant improvements post-intervention: 50% of participants showed enhanced visual perception in their blind field, while 70% exhibited increased reading speed. Importantly, these positive effects were sustained at the 6-month follow-up. A robust correlation emerged between 3D-MOT-IVR performance and improved visual perception in the blind field, emphasizing the intervention’s effectiveness.

CONCLUSION

These promising results lay a strong foundation for a larger randomized controlled trial, offering hope for a meaningful breakthrough in visual rehabilitation for this vulnerable population. Further studies are being developed to confirm these results and identify the most appropriate schedules to optimize visual outcomes (such as duration and repetition of these programs).
QOL-48. NEUROPSYCHOLOGICAL INTERVENTION FOR PEDIATRIC BRAIN TUMOR PATIENTS AND SURVIVORS - A PRE-STUDY WITH A FOCUS ON PATIENT INVOLVEMENT
Authors: Leiss Ulrike , Schneider Carina , Gsell Hannah , Maletzky Anna-Maria , Kienesberger Anita , Röhl Claas , Bocolli Albina , Gojo Johannes , Hansl Rita , Zettl Anna , Weiler-Wichtl Liesa J
Published: June 2024

BACKGROUND

Neuropsychological (i.e. cognitive, emotional and social) sequelae after pediatric brain tumors (PBT) can severely impair daily-life participation and consequently quality of life. Long-term access to appropriate interventions is therefore essential. Previous studies on effectiveness have recommended multi-component interventions tailored to the specific neuropsychological impairments and unique needs of the survivors. Hence, before conducting a new intervention study, we carried out a participative pre-study, in order to incorporate experienced needs of the group into a future concept.

METHODS

Known efficacy factors for neurocognitive interventions for PBT patients/survivors were analyzed in a systematic literature search (PubMed, PsychINFO and SCOPUS, 2000 -2024). In addition, a 3-part workshop (in total 4.5 days) was held with PBT survivors and carers (N=20) and Health-Care-Professionals (N=5). The “junior research academy” was designed to participatively run through the research process from the initial idea (how to improve interventions) to the study design.

RESULTS

After title and abstract screening only 27 studies remained for detailed analysis, with computerized/online cognitive training (mainly working memory), being the most frequently studied intervention, followed by exercise training. Single studies on the effect of medication, parent training, practice/strategy training and behavioral therapy, group training on social skills and neurofeedback were identified. Improvements in different domains have been shown, but recruitment often remains very difficult, as does the transfer to everyday life. Interestingly, the “junior research academy” developed in a slightly different direction: the winning projects (“family guide” or “everyday compass”) were primarily aimed at (1) providing quick and unbureaucratic information and support, (2) giving orientation in daily life, (3) helping to find appropriate interventions, and (4) providing emotional and organizational support.

CONCLUSIONS

A core group of the participating survivors and health-care-professionals will now finalize the development of an intervention with elements of both pillars and subsequently run a controlled trial.
SURG-03. VIRTUAL REALITY ASSISTANCE IN THE MANAGEMENT OF PEDIATRIC BRAIN TUMORS
Authors: Carai Andrea , Premuselli Roberto , Barba Matteo , Marasi Alessandra , Piccirilli Eleonora , Bua Antonella , Baldo Giada Del , De Benedictis Alessandro , D’Orazio Claudia , Cacchione Antonella , Savioli Alessandra , Marras Carlo E , Colafati Giovanna S , Mastronuzzi Angela
Published: June 2024

BACKGROUND

Virtual reality (VR) solutions are emerging as a useful adjunct to the armamentarium of the neurosurgeon. Surprisingly, little data is available in the literature regarding its utility in pediatric neurosurgical oncology. We hereby report our preliminary Institutional experience on the application of VR to surgical rehearsal in a series of pediatric brain tumors.

METHODS

Virtual models were obtained by the Surgical Planner (Surgical Theatre, Inc) in a series of 50 consecutive brain tumor cases treated at Bambino Gesù Children’s Hospital. Utility of VR was scored based on operators’ perception. Explored items included: planning, execution, resection, sparing of eloquent tissue, and overall surgical management. Scoring was performed using a customized Likert scale.

RESULTS

We prospectively collected 100 consecutive questionnaires from surgeons participating to brain tumor resection procedures. In a multivariate analysis VR was found to be significantly more beneficial in specific surgical settings. Leading surgeons (LS) judged VR significantly more useful in supratentorial tumors, in children younger than 10 years, and in planned partial resections. Assistant surgeons (AS) found VR more useful in supratentorial lesions, particularly in deep seated tumors. Both LS and AS perceived VR to be less useful for in embryonal tumors and epilepsy-associated gliomas (LEAT).

CONCLUSIONS

Our data suggest that VR technology is useful in the surgical management of children with brain tumors. There might be specific clinical scenarios in which the advantage of VR availability might have a significant clinical impact in planning and performing surgical resection.
NURS-04. MUSIC THERAPY WITH CAREGIVERS FOR THOSE WITH PEDIATRIC BRAIN CANCER AND BRAIN TUMORS: A CRITICAL REVIEW OF THE LITERATURE AND RECOMMENDATIONS FOR FUTURE PROGRAMS
Authors: Rizzo Deborah R
Published: June 2024

BACKGROUND

Caregivers for those with pediatric brain cancer and brain tumors face significant challenges. During the course of treatment, pediatric brain cancer and brain tumor patients face not just the physical consequences of treatments, but the neurological effects as well.

METHODS

This critical review of the literature examines the effects of Music Therapy on Caregivers, Caregivers for cancer patients, and Caregivers for pediatric cancer patients. A literature review was specifically chosen with the intention of making recommendations for future program planning. Subjects explored include the psychological, physical, and financial impacts of caregiving. Additional concepts include personality traits of Caregivers and multicultural considerations in caregiving. The topics of brain cancer and the use of Music Therapy with patients are also explored. Special attention is given to Music Therapy for Caregivers for those with pediatric brain cancer and brain tumors. Main points under this headline also include Caregiver stressors, similarities and differences in multicultural caregiving, and the limited research available to Caregivers.

RESULTS

At the time the literature review, no research had been conducted in the area of Music Therapy and Caregivers for pediatric brain cancer and primary brain tumors. Music Therapy was proven, however, to be a significant non-pharmaceutical intervention for several areas, including anxiety and pain management.

CONCLUSION

The conclusion drawn was that more research is needed with Music Therapy and this particular population. Additionally, a basic framework for a Music Therapy program for Caregivers for those with pediatric brain cancer and brain tumors has been provided with recommendations on the expansion of the program.
NURS-15. THE ROLE OF THE ADVANCED PRACTICE PROVIDER AND NURSES IN CLINICAL TRIALS
Authors: Schmus Cynthia , Briamonte Courtney Baker , Hoffman Carly , Holtzclaw Susan , McHugh Michele , Meyer Ashley , Raber Shannon , Rangan Kasey , Seidl Kenny , Strachan Marylynne , Waters Kaaren , Yeh-Nayre Lanipua , Higgins Micah
Published: June 2024

BACKGROUND

For many years clinical trials fell under the umbrella of medicine without much acknowledgement to the role of the nurse, both as advanced practice provider (APP) and staff nurse. Oncology continues to rank as one of the highest subspecialties when it comes to availability and participation in clinical trials. There remain multiple barriers to involvement including availability, lack of education, and medical mistrust. The specialized role and skill set of the APP and RN as part of the clinical trial team is important in overcoming these barriers.

METHODS

We distributed a survey to members of the Advanced Practice Provider and Nurse Investigator Committee (APPNIC), a group within the Pediatric Neuro-Oncology Consortium (PNOC), in order to identify themes, barriers to care, and opportunities for both the APP and RN within clinical trials. The use of a survey and interviews within our APPNIC cohort allowed us to collaborate on the nursing role, prioritize care in new and amended trials, and share unanticipated adverse effects and effective management.

RESULTS

APPs are actively involved with clinical trial enrollment, performance of diagnostic exams and procedures, education, and early recognition/management of adverse effects. There is also a growing theme of the APP as sub-investigator which provides value in facilitating consent, impacting accrual, determining eligibility, managing anticipated side effects. The role of the staff nurse in clinical trials is found to be vital in providing consistent communication/support, educating patients and families, and alleviating adherence and medical mistrust.

CONCLUSION

The APP and nurse have a specialized, relevant skill set, which when included as part of the multi-disciplinary team, has the ability to decrease barriers and increase overall delivery and safety of clinical trials. Our goal is to outline specific roles we feel should be standardized in the international arena for nursing involvement within clinical trials.
OTHR-08. CLINICAL MANAGEMENT OF TWO PEDIATRIC CASES OF INTRACRANIAL MESENCHYMAL TUMORS WITH FET::CREB FUSIONS
Authors: Lucas Bryony J , McGovern Susan L , Whitehead William E , Aldave Guillermo , Mohila Carrie A , Blessing Melissa M , Roy Angshumoy , Parsons D Williams , Chintagumpala Murali M , Okcu M Fatih , Lin Frank Y
Published: June 2024

BACKGROUND

Intracranial mesenchymal tumors (IMTs) with FET::CREB fusion are a newly described provisional entity lacking standard management options. This group of neoplasms occur in children and young adults, and is molecularly characterized by a FET family gene (most commonly EWSR1, rarely FUS) fused with a CREB family transcription factor (ATF1, CREB1, or CREM). Histologically, the Ki-67 index is typically low (<5%) and only rarely elevated (15-20%). Treatment consists of surgical resection. Cases achieving gross total resection (GTR) are observed without adjuvant therapy, while subtotal resection (STR) is followed by radiation therapy. Regardless of resection status, patients are at risk for local recurrence.

METHODS

Case report.

RESULTS

We present two patients with IMTs harboring FET::CREB fusions. Patient 1 is a 12-year-old male with a known left choroid plexus lesion and hydrocephalus, who presented with acute loss of balance, headaches, and emesis. CT head revealed progression of the choroid plexus lesion with intraventricular hemorrhage and worsening hydrocephalus. Following GTR of the tumor, pathology revealed an IMT without high-grade features and a Ki-67 index of 5%. RNA-sequencing revealed an EWSR1::ATF1 fusion. In consideration of GTR and the tumor being low-grade, he is being followed with surveillance scans. Patient 2 is a 14-year-old male who presented with headaches and seizures and was found to have an enhancing left occipital lesion on MRI. Following GTR, pathology revealed an IMT with abundant mitotic figures (15 per 10 high power fields), increased Ki-67 index of 30-40%, and a FUS::CREM fusion. Due to the high-grade histopathology, he was treated with focal proton beam radiotherapy (5400 cGyRBE). An MRI three months post-therapy was negative for tumor recurrence.

CONCLUSIONS

We describe two adolescents with IMTs harboring FET::CREB fusions and their management, including one with high-grade histology managed with upfront radiation therapy, which has not been previously reported in the literature.
OTHR-12. GENERATING A COMPREHENSIVE INTERACTIVE PEDIATRIC BRAIN TUMOR VISUALIZATION PORTAL FROM MOLECULAR AND CLINICAL DATA DERIVED FROM TWO MULTI-INSTITUTIONAL PROTOCOLS (SJMB03, SJYC07) AND NON-PROTOCOL PATIENTS TREATED AT ST JUDE CHILDREN’S RESEARCH HOSPITAL
Authors: Dhanda Sandeep K , Lu Congyu , Sioson Edgar , Liu Anthony P Y , Upadhyaya Santhosh A , Bagchi Aditi , Chiang Jason , Orr Brent A , Gajjar Amar , Smith Kyle S , Northcott Paul A , Li Qian , Zhou Xin , Robinson Giles W
Published: June 2024

BACKGROUND

Pediatric central nervous system (CNS) tumors represent a diverse group of neoplasms with heterogeneous molecular and clinical characteristics. The need for well-organized, searchable datasets is paramount to enhance our understanding and improve the treatment approaches for these devastating diseases. To illustrate this, we have organized multifaceted data from patients into an interactive portal equipped with cutting-edge visualization tools.

METHODS

Clinical and molecular data from the SJMB03 and SJYC07 protocols and select published non-protocol St. Jude patients were collated and harmonized. A data dictionary was constructed to record demographic information, treatment details, histology, methylation classification, mutations, chromosomal aberrations, and outcomes. We implemented five visualization techniques - summary plots, sample view, scatter plots, sample matrix, and survival plots. These techniques are interconnected, enabling interaction and “crosstalk”.

RESULTS

Data from 710 patients with CNS tumors were incorporated: 386 Medulloblastomas (MB); 88 Atypical teratoid Rhabdoid Tumors (ATRT); 54 Ependymomas (EPN); 49 Pineoblastomas (PB); 28 Embryonal Tumors with Multilayered Rosettes (ETMR), 22 Infant-type hemispheric glioma (IHG), 16 High grade glioma (HGG), 13 Choroid Plexus Tumors (CPT); 11 CNS Sarcoma; 8 CNS tumor with BCOR internal tandem duplication (CNS BCOR); 6 CNS neuroblastoma FOXR2 activated (CNS NB FOXR2); 5 Low grade glioma (LGG); and 24 other entities or unclassified tumors. The portal features enabled the creation of custom cohorts. For example, patients with TP53 mutations (n=32; 15 MB, 7 CPT, 6 HGG, 1 CNS Sarcoma, 1 CNS NB FOXR2, 1 PB, 1 unclassified tumor) or DICER1 mutations (n=10; 7 PB, 2 CNS Sarcoma, and 1 ETMR) could be identified, cross-compared and analyzed adjusting for variables at users’ choice.

CONCLUSION

The integration of molecular and clinical data from multiple sources into an interactive visualization portal presents a comprehensive resource for research and clinical practice. Future work will focus on expanding the portal to integrate more cases/cohorts.
OTHR-13. A RETROSPECTIVE ANALYSIS OF A CLINICO-PATHOLOGICAL DATA ON CHILDHOOD AND ADOLESCENT MENINGIOMA- A SINGLE CENTRE EXPERIENCE
Authors: Shaikh Tanveer Ahmed , Yasin Shireena , Hargrave Darren , Tan Enrica , Szychot Elwira
Published: June 2024

BACKGROUND

Meningiomas in young patients remain poorly understood in terms of their origin, outcomes, and best treatment approaches. Current knowledge is limited to small studies and applying adult data, making dedicated research crucial for better understanding and management of these tumours.

METHOD

We reviewed meningioma cases (1990-2023) from our database, analysing demographics, tumour details, treatment, and outcomes. Neuroimaging and records confirmed tumour location and resection extent. Pathology was reviewed for alignment with WHO 2016 classification.

RESULTS

At GOSH, 60 patients with meningioma were treated over 33 years. Ages ranged from infants (142 days) to young adults (21 years) of which 51.7% were males. The commonest tumour location was at the skull base (31.6%), followed by the convexity (23.3%). Notably, 6.6% were previously exposed to therapeutic irradiation, and 20% were diagnosed with neurofibromatosis type 2 (NF-2) while 3 others had suspected mosaic NF-2. Among 55 cases with slides available for histopathology review, 26 (46.42%) were WHO grade-I, while 25 (44.64%) WHO grade-II and 4 (7%) WHO grade-III which had a 50% fatality rate. Complete surgical removal offered the best outcome, with only 3 out of 29 patients (10%) experiencing relapse as compared to 11 out of 17 (64.7%) in those who underwent incomplete resection alone. However, radiotherapy after incomplete surgery showed promise, with all 8 patients remaining relapse-free. Unfortunately, the single patient with a very aggressive tumour type (rhabdoid histology) progressed even after complete removal and irradiation.

CONCLUSION

In children and teens with meningioma, extent of initial surgical resection is considered the strongest independent prognostic factor, but radiotherapy after incomplete removal can improve relapse-free survival. Careful monitoring is crucial for those with partial resections, high-grade tumours, or NF2. Molecular data may bring light in the future on how the unique characteristics of paediatric meningiomas impact clinical status, management approach and survival.
OTHR-20. MINIMALLY-INVASIVE MOLECULAR DIAGNOSIS OF INFILTRATING BRAINSTEM GLIOMAS THROUGH CEREBROSPINAL FLUID CELL-FREE DNA SEQUENCING
Authors: Hill* Katherine , Giantini-Larsen* Alexandra , Hickman Richard A , Holle Bridget M , Ucpinar Burcin Agridag , Alano Tina , Doe-Tetteh Seyram , DiNapoli Sara , Riviere-Cazaux Cecile , Burns Terence C , Haque Sofia , Young Robert , Thakur Sunitha , Bale Tejus , Rosenblum Marc K , Benhamida Jamal , Dogan Snjezana , Vanderbilt Chad , Borsu Laetitia A , Ross Dara , Chang Jason , Zampieri Caroline Barbosa , Donzelli Maria , Lin Andrew , Dunkel Ira J , Kramer Kim , Sait Sameer Farouk , Souweidane Mark M , Greenfield Jeffrey P , Berger Michael F , Arcila Maria E , Ladanyi Marc , Mellinghoff Ingo K , Karajannis Matthias A , Miller Alexandra M
Published: June 2024

BACKGROUND

Accurate molecular diagnosis of infiltrating brainstem tumors, including diffuse midline gliomas and IDH mutant astrocytomas, is essential for prognostication and optimal therapy. Surgical biopsy of the brainstem carries risk of permanent neurological deficits and may yield insufficient or non-diagnostic tissue. We hypothesized that minimally invasive “liquid biopsy” analyzing circulating tumor cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) could represent an alternative molecular diagnostic modality.

METHODS

We performed MSK-IMPACT, a New York State Department of Health authorized hybridization capture-based next-generation panel DNA sequencing clinical assay on 44 CSF samples from 37 unique patients with brainstem tumors. Ages at time of CSF collection ranged from 1–47 years (median: 29 years). For samples in which diagnostic alterations could not be detected, we performed a series of secondary analyses for known hotspot mutations such as H3F3A, IDH1/2, and BRAF, including manual review for mutant reads below the official clinical reporting threshold, as well as droplet digital PCR (ddPCR).

RESULTS

Among 44 samples included in this study, 10/44 (23%) samples had mutations detected by MSK-IMPACT using standard clinical calling criteria and 14 of the remaining 34 samples (41%) had supporting evidence of a diagnostically relevant mutation based on manual review. Testing by ddPCR was performed on 11 samples (based on DNA availability), uncovering 4 additional mutations. Overall positive diagnostic yield was 64% (28/44). In biopsied patients, CSF confirmed disease-defining mutations in 80% (16/20) of CSF samples, including H3F3A K28M (9/10; 90%) and IDH1/2 (5/6; 83%). Among 24 unbiopsied patients, a disease-defining mutation was identified in 60% (15/25) of CSF samples.

CONCLUSIONS

Analysis of CSF cfDNA in patients with brainstem tumors has a high diagnostic yield and obviates the need for tissue biopsy in a majority of patients. A tiered testing approach using next-generation sequencing and ddPCR assays helps maximize diagnostic information and sensitivity.
OTHR-21. DEVELOPING A NEURO-ONCOLOGY PROGRAM FOR ADOLESCENTS AND YOUNG ADULTS IN CANADA – THE CANON EXPERIENCE
Authors: Bennett Julie , Climans Seth , Das Sunit , Tsang Derek S , Massey Natalie , Tabori Uri , Hawkins Cynthia , Lim-Fat Mary Jane
Published: June 2024

BACKGROUND

Brain tumors are the leading cause of cancer-related death in adolescents and young adults (AYA). These tumors possess both pediatric-type and adult-type qualities, with up to 30% of gliomas harboring pediatric-type alterations. Specialized expertise and significant collaboration between pediatric and adult providers is needed to guide therapy for AYAs. To address this, we have developed the Canadian Adolescent and Young Adult Neuro-Oncology Network (CANON).

METHODS

In April 2021, we established a national virtual AYA tumor board integrating comprehensive molecular analysis of available tumors. Rounds included representatives from both pediatric and adult neuro-oncology, radiation oncology, neurosurgery, neuropathology and neuroradiology. We collected clinical data and recommendations from rounds.

RESULTS

In the first 2 years of rounds through CANON, 156 cases have been reviewed. Gliomas (108) accounted for most cases followed by medulloblastoma (18) and ependymoma (7). Sequencing was available in 47% of cases. Of those with molecular data available, the majority (36) had a pediatric-type alteration, followed by IDH mutation (10). Additional molecular analysis was recommended in 29% of cases presented. Of those with sequencing data available, 35% had a potentially targetable alteration identified. Despite this, only 8% were eligible for a clinical trial based on their diagnosis and age. Recurrent clinical questions included access to molecular analysis, use of “off-label” targeted agents, lack of clinical trial options for AYA patients and the practice variation in treatment of AYA tumors typically seen in childhood such as medulloblastoma and germ cell tumor.

DISCUSSION

Dedicated AYA rounds have highlighted many inequities in care of these patients, highlighting a need for inclusion of AYAs in clinical trials and further study of tumor biology and clinical outcomes of this cohort. AYAs with pediatric-type tumors would also benefit from management by dedicated physicians with expertise in these complex tumors.
OTHR-27. NARRATIVE MEDICINE APPLIED: A STUDY ELUCIDATING HOW ONE NEURO-ONCOLOGY TEAM GRAPPLES WITH DISTRESS
Authors: Riley Kathy , Toback Alison L , Knight Kelsey , Wimer Tammy , Coven Scott L , Tailor Jignesh K , Lion Alex H
Published: June 2024

BACKGROUND

Absorbing the cumulative weight of neuro-oncology patient stories in isolation leads providers to experience burnout and distress that some in our study called “debilitating.” Sands, Stanley, & Charon (2008) describe the field of pediatric oncology as one that “taunts professionals with the random unfairness” of grave childhood illness. They reason that clinicians in this demanding field may benefit from narrative training to build empathy, teamwork, and resilience. Narrative medicine is a rigorous and evidence-based field of study that utilizes the method of close reading of literature and art to engage providers in discussion and personal reflection. In narrative medicine workshops, participants immerse themselves in a text or image, contemplate their experiences and their relation to the text, write in response to a prompt, and share their writings with one another (Charon, et al., 2017).

METHODS

This study sought to understand how narrative medicine workshops conducted in a pediatric neuro-oncology clinical setting impacted individual team members, as well as inter- and intra-team relationships. Data collection for the study included pre- and post-surveys, qualitative interviews, and observation notes recorded by workshop facilitators. Researchers applied Clark’s (2014) framework of three distinct levels – relationship to oneself, relationship to the patient, and relationship to others on the team – to development of pre- and post-survey and qualitative interview questions.

RESULTS

Although quantitative data failed to demonstrate that the workshops reduced participant distress, qualitative research generated evidence that the very act of participating in narrative medicine workshops provided a safe space for providers to discuss job-related distress, breaking down hierarchical barriers and moving them toward what one participant called “professional intimacy.”

CONCLUSIONS

This research suggests that engaging in narrative medicine practice as a healthcare team may in and of itself alleviate distress and foster healing dialogue in a stressful clinical environment suffused with pain and loss.
OTHR-28. SUCCESS AND IMPACT IN 5 YEARS OF POST-MORTEM BRAIN TUMOR TISSUE PROGRAM: GIFT FROM A CHILD
Authors: Lyons Nicole , Nazarian Javad , Eze Augustine , Nourmohammadi Niku , Koptyra Mateusz , Resnick Adam , Minturn Jane , Frenkel Beth , Reingruber Sonora , Waanders Angela , Bornhorst Miriam , Williams Melissa , Monje-Deisseroth Michelle , Hysinger Jared , Liljensten Ann-Helen , Souweidane Mark , Greenfield Jeffrey , Campbell Cindy , Padilla Christopher , Smith Amy , Peck Sydney , Vitanza Nick , Leary Sarah , Stevens Jeff
Published: June 2024

The Gift From A Child post-mortem brain tumor tissue donation program was developed with patient families, care teams, and researchers to ensure patients can choose to donate brain tumor tissue regardless of logistics and circumstances. In the past 5 years, the program has developed a network of 7 Research Centers of Excellence (RCOE) that work with over 75 referring institutions, non-profit foundations, patient communities, and consortiums. Since the institution of this program, there has been an increase in the total number of donations. External donations also continue to grow as awareness builds, independent of new RCOEs joining the network. Program success is demonstrated by the increasing percentage of external donations and the number of new referral institutions each year. There has also been an overall increase in both total and percentage of donations from external referral sources, with an increasing majority of donations being external. From 2019 to 2023, the total number of external donations has jumped from 45 to 89 per year, reflecting an increase from 42% to 65% of the total donations. The referrals for external donations come from the treating neuro-oncology and general care teams, self-referrals from patient families directly, and from the patient family community on behalf of current patients. Resources are accessible via a 1-800 number, the GFAC website, and calls directly to RCOE or the GFAC team. Overcoming institutional and other logistical barriers ensures that all patients have access to GFAC. Patients who would otherwise be unable to donate are now represented in research that informs future treatments, leading to pre-clinical research that better represents the actual patient population. All data from donations via GFAC is shared with CBTN to ensure open access. This has led to an increase in successful projects and cell lines developed from the donated tissue.
OTHR-29. A SINGLE INSTITUTION REVIEW REGARDING TRENDS IN THE MOLECULAR ANALYSIS OF PEDIATRIC CENTRAL NERVOUS SYSTEM (CNS) TUMORS AND GERMLINE ANALYSIS BETWEEN 2019 – 2023, EMPHASIZING THE IMPORTANCE OF EASY ACCESS TO COMPREHENSIVE TESTING
Authors: Bendel Anne E , Skrypek Mary M , Galkowski Allison M , Pond Dinel A , Olson Damon R , Roiko Samuel A
Published: June 2024

BACKGROUND

Molecular characterization of pediatric CNS tumors improves diagnostic accuracy and guides treatment. Germline analysis is also important to uncover cancer predisposition syndromes, which influence the approach to treatment and tumor surveillance. The options for molecular assessment are influenced by availability, including access through a trial or insurance approval.

METHODS

A retrospective review of the molecular workup performed on all CNS tumors biopsied/resected at Children’s Minnesota from 2019 – 2023 was undertaken to look at trends in the specific tests performed over time and how the molecular results guided treatment.

RESULTS

Between 2019 – 2023, 220 patients at Children’s Minnesota were diagnosed with a CNS tumor. A total of 191 underwent surgery and 162 (85%) had sufficient tissue for molecular analysis. There was no apparent difference in the percentage of patients who underwent IHC/FISH/NGS between 2019 - 2023, but methylation profiling frequency increased over time (2019 2%, 2020 and 2021 10%, 2022 58% and 2023 71%). Frequency of germline analysis also increased (2019-2021 29%, 2022-52% and 2023-63%). Easy availability of comprehensive molecular and germline analysis for patients enrolled on COG-APEC14B1 is credited for these improving trends. Molecular analysis confirmed (59%) or supported (36%) the diagnosis, and guided treatment in 30% of cases (stratification of treatment in 89% of medulloblastoma and targeted treatment in 63% of high-grade glioma, 9% of medulloblastoma and 6% of low-grade glioma). Methylation profiling alone accurately diagnosed 79% of cases, including subtyping tumors. Germline analysis detected a pathogenic germline alteration in 14% of CNS tumor patients (NF1 5%; TP53 and BRIP1 1%; PALB1, NF2, TS2, SMARCB1, biallelic PMS2, CHEK2, FANCA, ORICH1 and SDHA 0.5%).

CONCLUSION

These findings demonstrate the importance of easy access to comprehensive molecular and germline analysis with quick turnaround time to provide the best diagnosis, prognosis and treatment options for pediatric CNS tumor patients.
PATH-01. ACCURATE AND RAPID PAEDIATRIC BRAIN TUMOR CLASSIFICATION (PBT) BY METHYLATION PROFILING USING NOVEL NATIVE REAL TIME OXFORD NANOPORE TECHNOLOGY SEQUENCING TECHNOLOGY
Authors: Feinberg Galina , Grunwald Assaf , Mark Nurit Gal , Maman Lena Shinderman , Shihrur Keren , Hameiri-Grossman Michal , Toledano Helen , Michaeli Orly , Fichman Suzanna , Izraeli Shai , Birger Yehudit
Published: June 2024

BACKGROUND

Pediatric brain tumors (PBTs) pose a significant challenge being the leading cause of cancer related mortality in children. The existing classification process is time-consuming and fails to capture the heterogeneity of PBTs. Urgent advancements in diagnostic and therapeutic approaches are needed. The WHO classification 5th edition for CNS tumors introduced DNA methylation analysis into the diagnostic process, especially for difficult-to-diagnose cases. However, the currently available DNA methylation array-based methods are laborious, costly, &require large amounts of DNA

METHODS

Nanopore methylation analysis is rapid, accurate, and inexpensive & requires minimal tissue. We applied this technology on 24 PBT samples that were classified into ten molecular subgroups.

RESULTS

Our results were compatible with those obtained through Heidelberg methylation analysis, standard histopathological examination, and molecular tests and were in concordance with the final neuro-pathological diagnosis. Moreover, for five prospective cases, that would have challenged standard methods, Nanopore yielded same-day results, guiding additional tests and providing a significant diagnostic advantage. In one case, a 2.2-year-old male, with a large left parieto-temporal tumor and a suprasellar lesioninitially treated elsewhere with upfront chemotherapy without biopsy, developed clinical deterioration. We resected the temporal lesion and frozen tissue diagnosis suggested low-grade glioma. However, same day Nanopore sequencing analysis indicated a high score for ‘Meningioma’. Final pathology examination 10 days later confirmed ‘‘Atypical meningioma, WHO grade 2” – an extremely rare diagnosis in this age group. Visual deterioration prompted immediate resection of the second lesion before final pathological confirmation. Thus, early Nanopore classification played a vital role in diagnosis and management.

CONCLUSIONS

Our preliminary results underscore the potential of Nanopore potential for accurate and rapid PBT classification from small brain biopsies, with DNA input as low as 100 nanograms. This cutting-edge technology promises to substantially reduce time to diagnosis, shaping future neurosurgical strategies for individualized PBT patient management.