bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 (&gt;23.4Gy/23.4Gy) resulted in lower scores for most domains for MB-patients compared to LGG-patients (e.g., PS-estimate: &gt;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

Abstract
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, &gt;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

Abstract
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 &gt; SKK only &gt; CSI only; p&lt;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 &gt;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

Abstract
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&lt;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.