bluuebunny/crossref_metadata_2025 huggingface dataset:
NFB-02. Maternal high-fat diet exposure increases the proliferation and glial differentiation of the cells of origin for NF1-optic glioma
Authors: Zhang Kailong , Gutmann David , Brossier Nicole
Published: June 2022

Some pediatric cancers arise in the context of tumor predisposition syndromes caused by germline mutations in genes that regulate cell growth. The most common of these syndromes, Neurofibromatosis type 1 (NF1), results in the development of low-grade tumors of the optic pathway (optic pathway gliomas; OPGs) in ~15% of affected children. However, risk assessment for each individual child is difficult, as it is currently challenging to predict which children with NF1 will develop OPG. Emerging human population-based evidence has raised the possibility that patient-specific risk factors, including infant birth weight, may modulate the risk of glioma development. High-infant birth weight can be modeled in mice by maternal exposure to a high-fat high-sucrose (HFHS) diet. To address the hypothesis that maternal high-fat diet exposure will increase the risk of OPG formation through intrinsic effects on the putative tumor cell of origin, we evaluated the effect of maternal exposure to a HFHS diet on the proliferation and differentiation of these cells (neural stem cells within the third ventricular zone; TVZ NSCs). Progeny from obese dams (MatOb) exposed to HFHS diet during and preceding gestation demonstrated increased proliferation and glial differentiation of TVZ NSCs in vivo. Similar results were observed with gestational HFHS diet exposure (GE) that did not result in maternal weight gain, suggesting these effects were related to maternal diet rather than weight. These effects were not observed in NSCs from other regions of the brain, supporting the regional specificity of the effect of diet on these tumor-initiating stem cells. Finally, we found that maternal HFHS diet resulted in elevated levels of leptin and insulin, both of which increase the proliferation of TVZ NSCs. Taken together, these findings provide early experimental evidence that maternal environmental exposure affects developing neural stem cells relevant to the risk of glioma formation.
NFB-03. Neurological manifestations in children and adolescents with Neurofibromatosis type 1 - Implications for management and surveillance
Authors: Angelova-Toshkina Daniela , Holzapfel Johannes , Bette Stefanie , Decker Josua , Hellmann Fabio , Traunwieser Thomas , Huber Simon , Schimmel Mareike , Vollert Kurt , Bison Brigitte , Kröncke Thomas , André Elisabeth , Wieczorek Dagmar , Gnekow Astrid K , Frühwald Michael C , Kuhlen Michaela
Published: June 2022

INTRODUCTION: We aimed to (1) characterize the spectrum of clinical phenotypes of NF1 in a random pediatric population, (2) correlate genotype with phenotypic expression for those with a genetic diagnosis, and (3) explore radiological features of NF1 in the central nervous system (CNS) by radiomics analyses to predict clinical course. METHODS: We performed a database search in the hospital information system of the University Children′s Hospital between January 2017 and December 2020 for patients with NF1 and evaluated the clinical phenotype by retrospective chart review. RESULTS: 75 children/adolescents were identified with suspicion/clinical diagnosis of NF1 (median age 10.0 years (range, 1.1-22.6); 35 female), confirmatory revised “diagnostic criteria” were met in 57 patients at the last follow-up. Per number of documented items, major signs were detected as 73/75 café-au-lait macules, 31/63 freckling, 38/71 neurofibromas (thereof 21 plexiform neurofibromas), 18/43 optic pathway glioma, 5/66 Lisch nodules, and two patients with sphenoid dysplasia. Genetic analysis (31/75) identified pathogenic NF1 variants in 27 patients. In 20/66 cases a parent met diagnostic criteria. Cognitive symptoms included developmental delay (28/68), learning deficits (12/48), attention-deficit hyperactivity disorder (3/53), and behavior anomalies (7/63). Classical unidentified bright objects were seen in 29/43, other intracranial tumors in 7/43, and cerebrovascular abnormalities in 5/43. Analysis of imaging features of the CNS in these patients will involve lesion segmentation and radiomics features. Symptomatic/progressive low-grade glioma necessitated neurosurgical resection (4/25) and/or chemotherapy (12/25). In 10/25 neuropsychological functions were assessed by the German neuropsychological basic diagnostic instrument. Until June 30th, 2021, one patient died of progressive plexiform neurofibroma.

CONCLUSIONS: A wide range of neurological manifestations, including neuropsychological deficits, should raise the suspicion of NF1 in an unselected pediatric population. We expect imaging features of the CNS to better predict the clinical course and enhance decision-making.
NFB-06. Laser Interstitial Thermal Therapy as a Radiation-Sparing Approach for Children with Cancer Predisposition
Authors: Guadix Sergio , de Silva Neranjan , Souweidane Mark
Published: June 2022

BACKGROUND: Li-Fraumeni (LFS) syndrome confers a predisposition for the formation of a broad range of tumors. Estimates of post-radiation secondary malignancy in the context of LFS cohorts range from 20-50%. Therefore, alternative therapeutic strategies are prioritized. Laser interstitial thermal therapy (LITT) is a minimally invasive technique utilizing thermal ablation for tumor control that is not associated with any ionizing radiation or known mutagenic effect. We describe the case of a child with LFS previously treated for CPC who developed a secondary low-grade glial neoplasm of the brain treated safely with MR-guided LITT as part of a radiation-sparing therapeutic approach. METHODS: Retrospective chart review identified a patient with recurrent CPC associated with LFS who was treated with LITT for a secondary low-grade glial tumor. A descriptive report is provided, including a review of clinical and radiologic outcomes of the procedure. RESULTS: A 4-year-old male with left parietal WHO Grade III CPC associated with a TP53 germline mutation met inclusion criteria. The patient underwent neoadjuvant platinum-based chemotherapy before near-total resection, followed by immunotherapy with 131I-8H9 and 30 fractions of 54Gy total proton therapy. He remained without evidence of disease for two years prior to developing a slow-growing mass adjacent to the left frontal horn. This lesion demonstrated radiographic progression on neuroimaging and was deemed to be a poor candidate for surgical removal. Stereotactic biopsy revealed a low-grade glial neoplasm staining positive for GFAP and Olig2. MR-guided LITT was concurrently performed for ablative therapy of the lesion without complication. Greater than 8-month follow-up has revealed no subsequent disease. CONCLUSIONS: Alternatives to ionizing radiation for brain tumors should be explored for patients with cancer predisposition, such as LFS. Long-term follow up will be needed to ensure local disease control and avoidance of treatment-related neoplasms.
NFB-07. Meningiomatosis in an adolescent with TRAF-7 mutation related syndrome
Authors: Torres Marleni , Jackson Nicole , O'Farrell Candelaria , Maher Ossama , Niazi Toba , Raghed John , Khatib Ziad
Published: June 2022

BACKGROUND: Meningiomas are rare primary brain tumors in the pediatric population, associated with multiple genetic mutations. Recent description of mutations in the TRAF7gene, a pro-apoptotic E3 ubiquitin ligase, have been found in up to one quarter of non NF-2 tumors. TRAF is downregulated in human keratinocytes after inhibition of the PI3K/AKT/mTOR signaling. Germ-line mutations in this gene are associated with facial, cardiac malformations, variable intellectual deficiency, and musculoskeletal abnormalities. OBJECTIVE: We report a case of meningiomatosis in an adolescent with TRAF 7 mutation. CASE PRESENTATION: A 17 yo female with complex medical history that includes syndactyly of the left foot, small hands and digits, congenital heart disease, overgrowth of the right lower extremity with lipomatous subcutaneous tumors, connective tissue disorder variant mutation of unknown significance in the gene Col11A2, conductive hearing loss developed meningiomas of both optic nerves requiring decompression and unroofing on two separate occasions, with associated blindness. MRI brain showed bilateral optic nerve sheath enhancement, dysplasia of the corpus callosum, mild hemimegalencephaly, inter-hemispheric fissure 1.5 cm meningioma, bilateral enhancement of internal auditory canals as well as trigeminal and glossopharyngeal nerve, consistent with menigiomatosis. Pathology showed a grade I meningioma with a TRAF7 p.G536S detected by performing a 500 genomic panel (UCSF500). She was started on Everolimus and Bevacizumab. CONCLUSION: Recurrent multiple meningiomas represent a treatment challenge for neuro-oncologists. The evolving understanding of the genetics of these tumors has improved our understanding of their pathogenesis as well as treatment. TRAF 7 mutations are associated with non-NF-2 meningiomas, and distinct phenotypic features. Germ-line testing should be considered in patients with associated malformations, as targeted therapy may improve patient outcomes.
NFB-14. Post-operative use of MEK inhibitors to prevent rebound growth following partial resection of plexiform neurofibromas
Authors: Chan Priya , Hemenway Molly , McMahon Kathleen , Dahl Nathan , Domeshek Leahthan , French Brooke , Foreman Nicholas
Published: June 2022

BACKGROUND: Plexiform neurofibromas (PNs) can cause significant morbidity leading to functional impairment, pain, and disfigurement. Management of PNs is challenging. Complete surgical resection is often not possible due to tumor growth along vital structures, and rebound growth is frequently experienced with partially resected PNs. The mitogen-activated protein kinase pathway has been implicated in the growth of PNs, and MEK1/2 inhibitors have been shown to be an effective treatment of PNs. OBJECTIVE: To describe our institutional experience using post-operative MEK1/2 inhibitors in the treatment of pediatric patients with PNs following subtotal resection (STR). METHODS: A single-institution retrospective record review. RESULTS: A total of 35 patients had STR of their PN. Fourteen patients underwent resection alone, ten patients received adjuvant mechanistic target of rapamycin (mTOR) inhibitors and eleven patients received adjuvant MEK1/2 inhibitors. The mean follow-up time was 5.1 years, but relatively shorter for patients receiving adjuvant MEK1/2 inhibitors. Mean time from resection to start of adjuvant therapy and mean duration of adjuvant therapy for patients in the mTOR inhibitor group was 3.3 weeks and 3.9 months, respectively, and for patients in the MEK1/2 inhibitor group was 3.1 weeks and 8.5 months, respectively. The number of patients in each group requiring additional treatment with surgical resection or medical therapy, was 11 of 14 patients (78.6%) in the resection only group, 7 of 10 patients (70%) in the adjuvant mTOR inhibitor group and 3 of 11 patients (27.3%) in the adjuvant MEK1/2 inhibitor group. CONCLUSIONS: A short course of MEK1/2 inhibitors following subtotal resection of PNs is effective in the short term in preventing rebound growth when compared to STR alone or adjuvant mTOR inhibitors. Treatment is well tolerated and should be considered as adjuvant therapy in pediatric patients. Long-term follow-up is necessary to judge the effectiveness of this approach.
NFB-21. Neurofibromatosis Type I in the Setting of Neuro-Oncology
Authors: Hemenway Molly
Published: June 2022

Neurofibromatosis Type I (NF1) is an autosomal dominant genetic syndrome that is inherited or sporadic. Neuro-Oncology nurses are experienced in the multidisciplinary care of NF1 patients due to an increased incidence of brain tumors and the treatment of plexiform neurofibromas with Mek inhibitors. However, these children are also at higher risk of rare solid tumors, specifically malignant peripheral nerve sheath tumors (MPNST). Most brain tumors in NF1 have a good prognosis. Conversely, MPNST has an extremely poor prognosis. While patients with MPNST are often cared for by solid tumor care teams, the identification and diagnosis of the tumors occur under the care of the neuro-oncology care team. Complex care coordination for patients with NF1 and cancer is required. Specifically, patients with NF1 are more sensitive to chemotherapy, have a higher incidence of radiation-induced secondary tumors, and need monitoring for NF1 related health impacts. Nurses and nurse practitioners with expertise in neuro-oncology, NF1, and solid tumors must collaborate to provide comprehensive care. Teaching tools and clinical strategies have been developed to maintain patients’ continuity with the primary oncology team while gaining the support of subspecialists. The genetic basis, inheritance pattern, and characteristics of Neurofibromatosis Type I will be discussed as well as rare oncologic diagnoses that are more prevalent in children/young adults with NF1. The multidisciplinary approach to the care of the patient with NF1 and a rare cancer diagnoses at a tertiary care center as well as the optimization of care of patients with NF1 and other underlying syndromes and rare cancers will be reviewed. Increased knowledge of NF1 and the associated health impacts and risk of cancers will improve the care of all patients with NF1.
NFB-22. Neurofibromatosis Therapeutics Program: Development of a Program
Authors: Hemenway Molly , Foreman Nicholas , Kristinsson Sara
Published: June 2022

Neurofibromatosis (NF) therapeutics is a vital field in the care of children with NF. Recent developments in the treatment of plexiform neurofibromas (PN) have increased the numbers of patients seen for therapy. The Neurofibromatosis Therapeutics Program (NTP) provides high quality care to patients receiving therapy for brain tumors and PNs, as well as tumors related to NF2. The program at Children’s Hospital Colorado (CHCO) includes a physician, nurse practitioner, and nurse care coordinator. The team collaborates with other disciplines in the care of the NF patient with plexiform neurofibromas and/or CNS tumors. As the program grew, key players were identified in each subspecialty and educated about the NTP. We have ongoing regular communication with a large number of subspecialists regarding protocols, clinical care pathways, and mutual patients. In addition, an extensive tissue collection study of plexiform neurofibromas and brain tumors enhances NTPs devotion to both clinical and lab research. Weekly clinical care meetings ensure continuity in the care of the nearly 140 patients with NF1 and NF2 under our program. Monthly strategy and vision meetings focus on grant applications, education of primary care providers and subspecialists in our large catchment area, development of new clinical pathways, treatment roadmaps, and growth of our program. Over the last two years of being a formalized program, we have increased research on the epigenetics of plexiform neurofibromas, opened a Phase 2 clinical trial for a Mek inhibitor, and increased our patient volume. The Covid pandemic has increased our ability to manage treatment side effects virtually through telehealth and online patient portals. Future goals of the NTP include completion of a program website, quarterly patient and provider newsletters, educational offerings, collaboration with other centers on Mek inhibitor side effects, adolescent and young adult education on tumor risk, and transition to adult care.
NFB-23. Extent of tumor but not location may be predictive of longitudinal disease severity in children with NF1-associated gliomas requiring treatment
Authors: Chaturvedi Sneha , Saxena Arohi , Hassan Ahmad , Brossier Nicole
Published: June 2022

BACKGROUND: Children with Neurofibromatosis Type 1 (NF1) are at risk for developing gliomas in multiple locations, particularly the optic pathway and brainstem. The goal of this study is to determine if glioma location in NF1 impacts tumor progression and accumulation of neurological deficits over time. METHODS: Retrospective chart review of 98 pediatric patients with NF1-associated gliomas between 1999-2021 at St. Louis Children’s Hospital. Patients who had never received treatment were excluded from analysis. Each glioma was categorized into one of four locations: posterior fossa (PF, n=12, 21%), supratentorial midline (SM, n=33, 57%) supratentorial cortical (SC, n=4, 7%), brainstem (BS, n=9, 15%). Patients with gliomas in different locations had each tumor counted separately (58 total gliomas analyzed). RESULTS: No SC tumors progressed. Time to first progression was comparable across the other 3 locations, and there was no meaningful different in neurologic deficits over time by tumor location. The majority of patients who demonstrated three or more clinical or radiographic progressions had tumors in the SM region. Within the SM tumor group, each tumor was further characterized as a deep extensive glioma (DEG; 36%) or an optic pathway glioma without deep extension (nonDEG; 64%). DEG had a slightly higher number of neurological deficits at baseline (DEG 2.08, nonDEG 1.19), fewer patients with no neurologic deficits (8.3% DEG vs 28.6% nonDEG) and a higher proportion of patients with a first progression event (41% DEG vs 24% nonDEG). However, DEG and nonDEG had similar risk of subsequent progressions after the initial event. CONCLUSION: Among children with NF1 who required glioma treatment, location was not a significant predictor of multiple progression or neurologic morbidity over time. Within the SM location, DEGs represent a newly characterized group that exhibit potentially higher rates of progression and neurological deficits. Multi-institutional analysis is needed to confirm these findings.
QOL-04. Histology, treatment, and extent of pretreatment hydrocephalus are major determents of neurocognitive outcome for survivors of pediatric posterior fossa tumors - report from the German HIT-studies
Authors: Neumann-Holbeck Anne , Traunwieser Thomas , Ozga Ann-Kathrin , Mynarek Martin , Kandels Daniela , Bison Brigitte , Kortmann Rolf-Dieter , Timmermann Beate , Pietsch Torsten , Thomale Ulrich-Wilhelm , Gnekow Astrid K , Rutkowski Stefan
Published: June 2022

BACKGROUND: Cognitive impairments following pediatric brain tumors are generally attributed to tumor site, surgical intervention, complications as well as to nonsurgical treatment. We investigated impairments for patients with medulloblastoma (MB), ependymoma (EP) and low-grade glioma (LGG) of the cerebellum treated within the German pediatric brain tumor network to compare and rank major determents. PATIENTS+METHODS: Following protocol treatment, 245 patients with MB (n=106), EP (n=32), and cerebellar LGG (n=107, surgery only) were examined 2 + 5 years after diagnosis using the German “Neuropsychological-Basic-Diagnostic” (NBD) tool based on the Cattell-Horn-Carroll model for intelligence. Within this retrospective study, multiple linear regression models were applied. RESULTS: The MB+EP vs. LGG-cohort differed slightly in median age at diagnosis (8.7/6.1 years) and location (cerebellar hemispheres: 8%MB+EP/49.5%LGG), while sex-ratio, grade of resection, extent of pre-operative hydrocephalus were comparable. With smaller median tumor-volume in the MB+EP vs. LGG-cohort (34.1/44.1cm3), ranges broadly overlapped. Median scores of age-appropriate tests were in the lower normal range for all patients for fluid and crystallized intelligence, selective attention, visual-spatial processing (VSP) and verbal short-term memory (median=93-103), but distinctly below for processing speed (PS), and psychomotor speed abilities (PMS) (median=65-84). Higher doses of craniospinal irradiation (>23.4Gy/23.4Gy) resulted in lower scores for most domains for MB-patients compared to LGG-patients (e.g., PS-estimate: >23.4Gy:-27.71, p=0.026/23.4Gy:-9.93, p=0.286). EP-patients (surgery+54Gy local radiation) scored better than LGG-patients except for PS (estimate:-15.65, p=0.111). Impairments were accentuated with higher degrees of hydrocephalus (estimate:-7.64, p=0.103) in patients with incomplete resection (estimate:12.23, p=0.006) for PMS both hands. CONCLUSION: Following age-adapted comprehensive treatment, survivors of a cerebellar tumor show significant impairments of PMS abilities in our trials. Our data suggest that slow growing LGG impair neurocognitive development more than local radiotherapy for ependymoma, while craniospinal irradiation compromises VSP and PS in MB. Initial symptomatic intracranial pressure remains a strong predictor for general neuropsychological impairment.
QOL-08. Visual memory and potential clinical risk factors in long-term survivors of a childhood brain tumor
Authors: Sleurs Charlotte , Lemiere Jurgen , Bullens Kristien , Jacobs Sandra
Published: June 2022

A brain tumor treatment has previously been associated with long-term neurocognitive sequelae. However, clinical profiles differ between certain patient subgroups. We investigated the impact of tumor location, radiotherapy (RT), and age at diagnosis in childhood brain tumor survivors on long-term cognitive outcomes. Adult survivors (n=32) of pediatric brain tumors (n=11 infratentorial, n=21 supratentorial; 14 astrocytomas, 3 craniopharyngiomas, 2 ependymomas, 2 germinomas, 1 hemangioblastomas, 4 medulloblastomas, 6 nervus opticus gliomas) participated in this neuropsychological study (n=11 RT) (16.8-35.1 years old, >2years after treatment, mean age at diagnosis = 9.2 years, 50% male). An extensive neurocognitive test battery was used to assess intelligence scales (n=5), verbal and visual memory (n=2), and language (n=3). In order to investigate the effects of tumor location (infra- versus supratentorial), RT (yes vs. no), and age at diagnosis on the cognitive scores, a multivariate ANCOVA model was tested including the main effects and interaction between age and RT. Of all included scales, only visual memory was significantly associated with the risk factors. More specifically, patients who received RT (F=10.3, p=.004) and were younger at diagnosis (F=6.9, p=.014) scored worse on this task. Furthermore, the interaction effect between these factors was also significant (F=8.8, p=.006). These findings suggest that younger patients could be more vulnerable to the radiotoxic effects to visual memory outcomes. Tumor location (supra- vs. infratentorial) was not significantly associated with any outcome. In this study, only visual memory appeared to be associated with the risk factors of interest. Both radiotherapy and age at radiotherapy, as well as their interaction, could be risk factors for altered neurodevelopmental patterns of brain areas associated with visual memory.
QOL-10. Treatment-induced leukoencephalopathy in pediatric medulloblastoma survivors and its impact on long-term neurocognitive functioning
Authors: Wägner Lukas , Bison Brigitte , Neumann-Holbeck Anne , Tischler Tanja , Guiard Anika , Obrecht Denise , Ottensmeier Holger , Kortmann Rolf-Dieter , von Hoff Katja , Schlegel Paul-Gerhardt , Remke Marc , Redlich Antje , Holzer Ursula , Blattmann Claudia , Fleischhack Gudrun , Sander Annette , Jorch Norbert , Becker Martina , Karremann Michael , Frühwald Michael C , van Buiren Miriam , Struve Nina , Warmuth-Metz Monika , Rutkowski Stefan , Mynarek Martin
Published: June 2022

OBJECTIVES: Leukoencephalopathy (LEP, i.e. white matter T2-/FLAIR-hyperintensities on MRI) and impaired neuropsychological outcome are side effects of multimodal therapy of medulloblastoma. We identified risk factors for LEP and correlated LEP with neurocognitive functioning. PATIENTS AND METHODS: Severity of LEP either at the end of therapy (n=118), two years (n=126), or five years after surgery (n=139) was evaluated according to an adapted Fazekas classification for 162 survivors of medulloblastoma (median age: 7.4 years [range:0.67-19.8 years]). Severity of LEP two or five years after surgery was correlated with treatment and neurocognitive functioning ≥ five years after diagnosis using univariate analyses and multivariate generalized mixed linear models. RESULTS: Two and five years after surgery, incidences of mild/moderate/severe LEP were 21.4%/17.5%/9.5%, and 24.5%/23.7%/8.6%, respectively. Data on severity of LEP both at the end of therapy and five years after surgery was available for 103 patients: LEP grades increased for 1/2 degrees in 18/4 patients and decreased in 13/1 patients, respectively. Both treatment approaches - HIT-SKK chemotherapy including intraventricular methotrexate (SKK) and craniospinal irradiation (CSI) - were associated with increased severity of LEP (CSI+SKK > SKK only > CSI only; p<0.001). Severe LEP only occurred in patients treated with both CSI and SKK. In total 19% of all patients treated with this combination developed severe LEP. Severe LEP correlated with impaired fluid (p=0.013) and crystalline (p=0.012) intelligence and short-term memory (p=0.024) on both univariate level and in multivariate mixed linear models. Among patients treated with CSI doses >30Gy, severe LEP, but not SKK including intraventricular MTX, correlated with impaired neurocognitive functioning. CONCLUSION: After therapy strong changes in LEP rarely occurred. Severe LEP was associated both with the combination of SKK and CSI, and impaired neurocognitive functioning. Further research will be needed to weigh potential benefits of SKK including intraventricular methotrexate with CSI against its neurotoxicity.
QOL-13. Impact of hearing loss on neuropsychological functioning in children treated for medulloblastoma: A report from the Children’s Oncology Group (COG)
Authors: Embry Leanne , Hardy Kristina , Orgel Etan , Wang Yu , Michalski Jeff , Li Yimei , Cullen Patricia , Colte Paul , Bass Johnnie
Published: June 2022

BACKGROUND/OBJECTIVE: We prospectively examined neuropsychological outcomes and ototoxicity in children with average-risk medulloblastoma. METHODS: Eligible patients included those treated on COG protocol ACNS0331 who completed audiograms at end of therapy or one-year off-therapy, and neuropsychological assessments between 2- and 5-years post-diagnosis. Conventional pure-tone audiometric evaluations (0.25-8kHz) were assigned an ototoxicity grade based on the International Society of Pediatric Oncology (SIOP) grading scale. Grade for the better hearing ear was used for analyses. Participants were divided into two groups: SIOP grade≥3 hearing loss (HL) versus SIOP grade<3. Cutoff score of 60 on BASC-2 was used to dichotomize parent-reported anxiety and depression scores as ‘low’ or ‘high’. RESULTS: Data were available for 113 children (66% male; 86% white), aged 3.0-18.5 at diagnosis (Mean=9.1). One-quarter (24.8%, n=28) had at least moderate HL (≥ SIOP grade 2), and 12.3% (n=14) had severe HL (≥ SIOP grade 3). After controlling for radiation exposure and age, children with severe HL showed significantly higher levels of anxiety (OR=5.9, 95%CI 1.3-26.0, p=0.0195) and borderline differences in depression (OR=4.0, 95%CI 1.0-16.5, p=0.0563), but no differences in cognitive functioning when compared to other participants. When moderate and severe HL were combined in exploratory analyses, significantly greater anxiety (OR=9.0, 95%CI 2.1-37.4, p=.0027) and depression (OR=4.6, 95%CI 1.3-15.7, p=.0165) were observed. CONCLUSIONS: Survivors of pediatric medulloblastoma with moderate to severe HL evidenced greater psychosocial, but not neurocognitive, difficulties compared to those with no or mild HL. It may be that modern treatment protocols generally preserve cognitive functioning such that associations between HL and cognitive impairment are no longer significant. It is also possible that neurocognitive risk associated with HL may not manifest until survivors are further from diagnosis. In contrast, survivors with HL may be at greater risk for negative psychosocial adjustment, suggesting that increased monitoring of mental health outcomes is warranted.
QOL-15. Life happens wherever you are! Use of Avatar AV1 to enhance Health-Related Quality of Life, Sense of Belonging and Social Inclusion in Children and Adolescents with Chronic Illnesses
Authors: Pletschko Thomas , Pelzer Clarissa , Röhsner Martin , Rockenbauer Gerda , Turner Agnes
Published: June 2022

BACKGROUND: Due to regular hospital check-ups, inpatient treatments, or a weakened immune system, children with brain tumors experience frequent and long absences from school and social activities. Returning to school presents a challenge for these patients, as they experience reduced health-related quality of life (HRQOL), decreased sense of belonging and a lack of social inclusion in class. To prevent social and emotional problems, telepresence systems such as the Avatar AV1 are described as promising approach for pediatric patients. OBJECTIVES: To sustainably improve social inclusion in times of illness-related absence for these patients, the first study in Austria investigating effects of the use of the Avatar is pursuing both, a qualitative and quantitative approach. METHODS: To examine effects on social inclusion, sense of belonging and HRQOL in pediatric patients, interviews were conducted with patients, their parents, teachers and classmates within the qualitative approach and questionnaires were administered at three times (before -, after 6 months Avatar-use and 3 months after returning the Avatar) within the quantitative approach. The sample consists of pediatric patients (6 to 18 years). RESULTS: Categories from n=24 interviews indicate that a positive attitude towards and identification with the Avatar as well as the patients’ psychological condition and social inclusion into class before the illness play major roles. Preliminary findings from the ongoing longitudinal quantitative survey indicate that the Avatar has significant positive and stabilizing effects on HRQOL, sense of belonging and social inclusion of pediatric patients. CONCLUSION: This study is the first to describe the impact of Avatar use on social inclusion in children with brain tumors. To strengthen the sense of belonging in these children, the pedagogical-interactional component needs to be brought in focus. Through pedagogical-didactical adaptions, a routine handling of and a positive attitude towards the telepresence system, pediatric patients highly benefit from the Avatar.
QOL-17. Neurocognitive outcomes after treatment for medulloblastoma with reduced primary site target volume margins
Authors: Larkin Trisha , Lin Tong , Ashford Jason M , Onar-Thomas Arzu , Gajjar Amar , Conklin Heather M , Merchant Thomas
Published: June 2022

PURPOSE: Children treated for medulloblastoma (MB) undergo intensive multimodality treatment compromising surgery, irradiation, and chemotherapy, which is associated with a significant risk of neurocognitive deficits. Successive multicenter frontline treatment protocols have introduced reduced posterior fossa boost margins for cranial irradiation for sparing collateral tissue and preserving function. This study examines neurocognitive outcomes in the setting of reduced primary site target volume margins in children treated for MB. PATIENTS & METHODS: Prospective longitudinal neurocognitive data were collected from newly diagnosed patients with MB (n = 372, ages 3-21 years) enrolled on one of two sequential multicenter clinical protocols between 1996 and 2012. The treatment regimen included surgery, risk-adapted craniospinal irradiation with a posterior fossa boost with restricted clinical target volume (CTV) margins (2 cm and 1 cm), and dose-intensive chemotherapy. Comparative analysis of neurocognitive outcomes was performed using linear mixed-effects models. RESULTS: Intelligence quotient (IQ) scores were better preserved in average-risk patients who received treatment using a clinical target volume with a lesser margin of 1 cm (p < 0.0099). Findings were consistent with prior studies on measures of academics including reading performance, mathematical reasoning, and spelling across both risk groups regardless of CTV. CONCLUSION: This study presents compelling evidence in favor of restricted CTVs for preserving IQ without sacrificing treatment efficacy in average childhood MBs.
QOL-18. Neuropsychological screening in a pediatric neuro-oncology multidisciplinary clinic.
Authors: Mietchen Jonathan , Kessler-Jones Alanna , Damodharan Shawn , Puccetti Diane
Published: June 2022

BACKGROUND: The purpose of this project was to examine the usefulness of neuropsychological screening in a multidisciplinary clinic for neuro-oncology populations and determine whether a brief evaluation can adequately screen children for cognitive dysfunction or psychiatric comorbidities. METHODS: Thirty-one children or young adults with a history of CNS tumor had neuropsychological screening as part of their multidisciplinary clinic visit. This screening evaluation consisted of clinical interview, neuropsychological testing, and the completion of emotional/behavioral checklists. Our neuropsychological test battery included the Kaufman Brief Intelligence Test-Second Edition (KBIT-2) and the NIH Toolbox Fluid Cognition Composite, which consists of 6 subtests - flanker task, working memory, processing speed, oral reading, card sort, and memory. RESULTS: Over a 15-month period 31 children, adolescents, and young adults with CNS tumors were seen in our neuropsychology screening clinic. Females made up 39% of the sample. The average age was 12.7 years (range=5–24 years). The average time to complete neuropsychological testing was 60.3 minutes. Thirty-six percent did not have any new neuropsychological diagnoses, 42% had one new diagnosis, 19% had two new diagnoses, and 3% had three new diagnoses. The most common new diagnoses were mild or major neurocognitive disorder (mild=29%, major=6%), anxiety (32%), ADHD (10%), and mood disorder (13%). Neurocognitive test scores were mostly in the average range (Verbal-IQ=97.7; Nonverbal-IQ=95.3; Total IQ=96.2; Flanker T-Score=46.1; Working Memory T-Score=44.0; Card Sort T-Score=43.7; Picture Memory T-Score=48.5). Processing speed and fluid cognition composite scores for the group were in the low-average range (Processing Speed T-Score=42.7; Fluid Cognition Composite T-Score=41.4). Behavioral health recommendations were needed for 71% of this sample. Educational recommendations were needed for 58%. CONCLUSIONS: Brief neuropsychological screening completed as part of multidisciplinary clinics for pediatric neuro-oncology patients was efficient and useful in identifying neuropsychological diagnoses in children and assisted with informing necessary behavioral health and academic interventions.
QOL-20. Post-Intensive-Care Syndrome – pediatric (PICS-p) among patients with brain tumors – therapeutic strategies and preventive recommendations
Authors: Korzeniewska Justyna
Published: June 2022

BACKGROUND: Patients with brain tumors needed in intensive care unit (ICU) stay due to tumors symptoms or neurosurgery, experience a complex of physical, psychological, and cognitive symptoms. This constellation of signs and symptoms has been named Post-Intensive-Care Syndrome – pediatric (PICS-p). An interesting problem emerging from this research and requires a deeper exploration are the differences between PICS-p symptoms and primary tumors effects or side effects of treatment e.g. irradiation. METHOD: Psychological repeated testing and long-term observation was performed in 350 childhood brain tumor survivors (various types and localizations of tumor) to determine PICS-p symptoms. Age at psychological diagnosis ranged from 6 to 20 years. Full psychological outcome included assessment of psychophysical, cognitive and affective problems. The patients were examined using battery of neuropsychological methods and psychological interview. Analysis of medical history was also performed. The next level of the study was distinguished between PICS-p symptoms and the effects of tumor localization and oncology treatment, including radiotherapy. RESULTS: In our sample patients presents low scores in the all PICS-p domains: physical, cognitive and mental. Low level of motor skills, impairing daily living activities are characteristic. In this group lower IQ scores, poorer visual motor integration, learning disabilities, memory and language problems persisted. Typical problems in mental area are depressive symptoms, anxiety with intrusive memories, emotional and behavioural disruptions, socialization problems with significantly low level of social contacts. CONCLUSIONS: The results of this study suggest that PICS-p well describes and explains the psychosocial problems of these patients. It allows prepare an individual psychological interventions and rehabilitative program for particular patient as well as therapeutic strategies for whole group of patients. Draft recommendations for diagnosis of PICS-p specific for patients with brain tumors, risk factors and preventive procedures will be presented and discussed.
QOL-26. Exploring the experience of young people receiving remotely delivered Acceptance and Commitment Therapy following treatment for a brain tumour
Authors: Powers Katie , Airdrie Jac , Thomas Sophie , Gibson Faith , Geagan Chloe , Davies Nic , Malins Sam
Published: June 2022

Despite high survival rates of children and young people diagnosed with a brain tumour, survival is often associated with poor psychological, physical, and social outcomes. Acceptance and Commitment Therapy (ACT) is an evidence-based psychological intervention shown to improve psychological and physical outcomes in adults and children with chronic disease, including cancer. The ACT Now study investigates the feasibility of ACT delivered remotely with young people who have experienced a brain tumour. This study aims to describe participant experience whilst better understanding the impact of therapy and capturing the barriers and facilitators to engagement. Participants of the ACT Now study were invited to take part in a semi-structured interview with questions covering experience of study initiation, receipt of ACT, remote delivery and overall impact of ACT. Ten participants who had previously undergone treatment for a brain tumour have been interviewed to date. Interviews were transcribed verbatim and coded into broad themes. We found that pre-therapy mood and altruism served as motivation for interviewees’ involvement in the study. Interviewees reported hoping to learn coping techniques to navigate fluctuating moods and the pressures of young adult life. Despite the technology used for remote delivery occasionally malfunctioning, interviewees reported increased ability to access therapy via this method. However, an overall preference for face-to-face therapy delivery was reported with interviewees describing that they felt communication might have been easier in person. The therapeutic relationship and the therapists’ flexible schedules were seen as facilitators to session attendance. Barriers to attendance were scarcely reported but included scheduling conflicts due to work or school. ACT was highly regarded amongst interviewees and provided an opportunity for them to learn about themselves and how they can live in accordance with their personal values. Interviewees benefitted from ACT psychologically, physically, and socially and reported an overall positive experience of study involvement.
QOL-29. Neuropsychology for you“ – tools to improve awareness of and access to neuropsychological care
Authors: Weiler-Wichtl Liesa Josephine , Fohn-Erhold Verena , Kollmann Alina , Fries Jonathan , Schneider Carina , Holzer angelika , Rosenmayr Verena , Schreiber-Gollwitzer Beate , Lüttich Peggy , Ross Henning , Pletschko Thomas , Hopfgartner Maximilian , Leiss Ulrike
Published: June 2022

OBJECTIVE: The occurrence of neuropsychological late effects in childhood brain tumor patients is well known in literature and practice, as well as the use of neuropsychological testing and therapy procedures. Despite guidelines, actual care is quite heterogeneous and often does not meet the needs due to lack of resources. Therefore, a standardized tool to improve awareness of and access to neuropsychological assessment, but even more treatment was developed. METHODS: The core of this Quality-Improvement project is a multilevel and interdisciplinary approach characterized by iterative processes (PDSA-cycles): (1) conceptualization by interdisciplinary, multicenter teams of experts, (2) consensus in Delphi surveys by medical, nursing and psychosocial experts (N=45) and final approval by the steering group. (3) Pilot phases (N=44): Manageability and acceptance, emotional well-being and the degree of information were recorded using a process-oriented screening. RESULTS: The expert meetings resulted in two booklets ("Look closely - Psychosocial assessment" & "1,2,3 - All about Neuropsychology"): Each booklet offers creative methods with a high prompting character to motivate the child to participate actively in two face-to-face sessions (psychoeducational, work and exercise and reflection section). They enable patients to make themselves experts on these topics with age-appropriate, interactive methods. The Delphi survey revealed a consensus of 69%-93%. Patients using the Psychosocial-assessment booklet showed generally low negative emotions and stable positive emotions, which significantly increased during the second session (Z = 2.156, p = .031). Moreover, positive emotions increase significantly during the second session (Z = 2.805, p = .005). Self-indicated degree of information increases significantly with both booklets (Psychosocial assessment: Z = 3.133, p = .002; Neuropsychology: Z = 2.751, p = .006). CONCLUSION: The results illustrate a positive emotional approach to neuropsychological assessment and treatment. Likewise, the rapid increase in expert knowledge supports access to this specific topic and can be considered a minimum standard.
SURG-01. The Tentative Application of En Bloc concept in the Pediatric Brain Tumor: A Retrospective Study of 171 Cases from A Large Pediatric Center in China
Authors: Cao Liangliang , Tian Shuaiwei , Zhao Yang , Wang Baocheng , Wang Jiajia , Ma Jie
Published: June 2022

BACKGROUND: The less allowable blood loss and tolerance of intraoperative blood loss of children lead to the high rate of massive blood transfusion. The surgical concepts of en bloc resection may contribute to the improvement of brain tumor resection. OBJECTIVE: To investigate the effects of en bloc concept on short outcomes of pediatric brain tumors and factors associated with the application of en bloc concept. METHODS: According to the surgical concept involved, the patients were divided into three subgroups-complete en bloc concept, partial en bloc concept and piecemeal concept. The matching-comparison(en bloc group consisting of the first two subgroups and piecemeal group) was conducted to investigate the effect of the en bloc concept on the short-term outcomes. Then the patient data after January 2018, when the en bloc concept was routinely integrated into brain tumor surgery in our medical center, were reviewed and analyzed to find out the predictors associated with the application of en bloc concept. RESULTS: In the en bloc group, the perioperative outcomes, including hospital stay(p=0.001), PICU stay(p=0.003), total blood loss(p=0.015), transfusion rate(p=0.005) and complication rate(p=0.039), were all significantly improved. The multinomial logistic regression analysis showed that tumor volume, bottom vessel, and imaging features, like encasing nerve or pass-by vessel, finger-like attachment, ratio of “limited line” and ratio of “clear line” remained independent predictors for the application of en bloc concept in our medical center. CONCLUSION: The application of en bloc concept based on the imaging features can improve the short-term outcomes.
SURG-02. The site of origin of medulloblastoma: Does the neurosurgical perspective support the current concept from molecular data?
Authors: Ciobanu-Caraus Olga , Cho Anna , Kasprian Gregor , Peyrl Andreas , Haberler Christine , Slavc Irene , Frischer Josa M , Czech Thomas , Rössler Karl , Gojo Johannes , Dorfer Christian
Published: June 2022

BACKGROUND: Medulloblastoma (MB) are the most common malignant brain tumor in childhood. Developmental gene expression data supported by neuroradiological studies suggest that Wingless (WNT)-MB originate from the lower rhombic lip (LRL), Sonic-Hedgehog (SHH)-MB from the cerebellar hemispheres, and Group 3 and Group 4 MB from the cerebellar vermis. However, there is still insufficient evidence from a neurosurgical perspective supporting this proposed concept. METHODS: Clinical and molecular data from patients aged under 18 years at time of diagnosis who were operated on a histologically confirmed MB at the Department of Neurosurgery of the Medical University of Vienna between 1990 and 2020 were retrospectively analyzed. The location of the tumor origin was defined based on operative reports, surgical videos and preoperative imaging data by an experienced neurosurgeon blinded to the subgroup information. RESULTS: Sufficient data were available in 53 patients. In 28.6% (2 / 7) WNT-MB, 66.7% (6 / 9) SHH-MB and 70.3% (26 / 37) Group 3 and Group 4 MB, the intraoperatively defined site of origin corresponded well with the cellular origin suspected from the molecular subgroup. Within the WNT-subgroup, 57.1% (4 / 7) originated from the vermis, 28.6% (2 / 7) from the LRL and 14.3% (1 / 7) from the cerebellar hemisphere. The origin of SHH-MB was predominantly located in cerebellar hemispheres (66.7% (6 / 9)), while 33.3% (3 / 9) originated from the vermis. Of Group 3 and Group 4 MB, 70.3% (26 / 37) had their origin in the vermis and 29.7% (11 / 37) in the LRL.CONCLUSION: Our results indicate that there is a considerable level of inconsistency between the intraoperatively observed site of origin and the expected cellular origin based on the molecular subgroup, especially in WNT-MB. This discrepancy needs to be discussed when it comes to surgical decision-making accounting for risk stratification.
SURG-05. Survival and functional outcomes in pediatric thalamic and thalamopeduncular low grade gliomas
Authors: Benes Vladimir , Zapotocky Michal , Liby Petr , Taborsky Jakub , Blazkova Jr. Jana , Blazkova Sr. Jana , Sumerauer David , Misove Adela , Pernikova Ivana , Kyncl Martin , Krskova Lenka , Koblizek Miroslav , Zamecnik Josef , Bradac Ondrej , Tichy Michal
Published: June 2022

BACKGROUND: Childhood thalamopeduncular gliomas arise at the interface of thalamus and cerebral peduncle. The optimal treatment is total resection but not at the cost of neurological function. We present long-term clinical and oncological outcomes of maximal safe resection. METHODS: Retrospective review of prospectively collected data: demography, symptomatology, imaging, extent of resection, surgical complications, histology, functional and oncological outcome. RESULTS: During 16-year period (2005-20) 21 patients were treated at our institution. These were 13 girls and 8 boys (mean age 7.6 years). Presentation included progressive hemiparesis in 9 patients, raised intracranial pressure in 9 patients and cerebellar symptomatology in 3 patients. The tumor was confined to the thalamus in 6 cases. Extent of resection was judged on postoperative imaging as total (6), near-total (6) and less extensive (9). Surgical complications included progression of baseline neurological status in 6 patients, 5 of these gradually improved to preoperative status. All tumors were classified as low-grade gliomas. Disease progression was observed in 9 patients (median progression free survival 7.3 years). At last follow-up (median 6.1 years) all patients were alive; median Lansky score of 90. Seven patients were without evidence of disease, 6 had stable disease, 7 stable following progression and 1 had progressive disease managed expectantly. CONCLUSION: Pediatric patients with low grade thalamopeduncular gliomas have excellent long-term functional and oncological outcomes even when gross total resection is not achievable. Surgery should aim at total resection; however neurological function should not be endangered due to excellent chance for long-term survival.