Predictors of Seizure Outcome After Epilepsy Surgery in Pediatric Patients With Low-Grade Developmental and Epilepsy-Associated Brain Tumors.

Background: Low-grade developmental and epilepsy-associated brain tumors (LEATs) are common causes of childhood-onset drug-resistant focal epilepsies. Although epilepsy surgery shows favorable outcomes in most patients, approximately 20%-30% of them do not become seizure free. This study aimed to identify predictors of postoperative outcomes and seizure recurrence, either spontaneously or after antiseizure medication (ASM) tapering, in a pediatric cohort with LEATs.

BRAF V600E Mutation in Ganglioglioma: Impact on Epileptogenicity and Implications for Surgical Strategy.

Objective: Gangliogliomas are commonly found pathologies in patients undergoing epilepsy surgery. While resections can be curative, seizure relapses occur. Expression of CD34 and the BRAF V600E mutation are the most common molecular biomarkers found in gangliogliomas, but their influence on seizure outcomes is unclear.

Effective targeting of PDGFRA-altered high-grade glioma with avapritinib.

PDGFRA is crucial to tumorigenesis and frequently genomically altered in high-grade glioma (HGG). In a comprehensive dataset of pediatric HGG (n = 261), we detect PDGFRA mutations and/or amplifications in 15% of cases, suggesting PDGFRA as a therapeutic target. We reveal that the PDGFRA/KIT inhibitor avapritinib shows (1) selectivity for PDGFRA inhibition, (2) distinct patterns of subcellular effects, (3) in vitro and in vivo activity in patient-derived HGG models, and (4) effective blood-brain barrier penetration in mice and humans.

[Plastic surgical treatment of neurofibromatosis type 1].

Neurofibromatosis type 1 (NF1, formerly Recklinghausen's disease) is a genetic tumor predisposition syndrome in which the mutation of a tumor suppressor gene (neurofibromin) leads to the development of mostly benign neurofibromas of the skin and the central and peripheral nervous systems and malformations or tumors of other organ systems. Patients with NF1 should receive lifelong interdisciplinary care in specialized centers and important treatment decisions should be made by a regularly meeting interdisciplinary panel of experts. Plastic surgery plays an important role in the multidisciplinary management of all clinical forms of NF1-associated peripheral nerve sheath tumors, from cutaneous and subcutaneous to deep nodular and diffuse plexiform neurofibromas.

Alternative lengthening of telomere-based immortalization renders H3G34R-mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens.

Background: Diffuse hemispheric glioma, H3 G34R/V-mutant (DHG-H3G34) is characterized by poor prognosis and lack of effective treatment options. DHG-H3G34R further harbor deactivation of alpha-thalassemia/mental retardation syndrome X-linked protein (ATRX; DHG-H3G34R_ATRX) suggesting a unique interaction of these 2 oncogenic alterations. In this study, we dissect their cell biological interplay, investigate the impact on telomere stabilization, and consequently validate a targeted therapy approach.

Consensus recommendations on management of selumetinib-associated adverse events in pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas.

Background: Selumetinib is the first approved treatment for pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN) in the EU and US, as well as in multiple other countries. Evidence for the management of selumetinib-associated adverse events (AEs) is mostly limited to clinical trials and expanded-access programs. We gathered a panel of European healthcare practitioners with clinical experience prescribing selumetinib and/or managing pediatric patients with NF1-PN to provide recommendations on the prevention and management of AEs.

Neurofibromatosis type 1 adult surveillance form for Austria.

Background: Neurofibromatosis type 1 (NF1) is a rare autosomal dominant tumor predisposition syndrome with a birth prevalence of approximately 1 in 2000-3000 individuals. Management of both benign and malignant tumors arising in individuals with NF1 is demanding and tumors may be difficult to treat. Both standardized and individual surveillance programs are therefore highly important to prevent morbidity and mortality in patients with NF1.

Accelerated Linear Growth during Erdafitinib Treatment: An FGFR-Related, but Growth Factor and Sex Steroid-Independent Mechanism?

Introduction: Growth acceleration during postnatal growth only occurs during puberty as a physiological event and during catch-up growth mediated by growth-promoting therapies in growth disorders. Here we report on novel observations of skeletal symptoms during treatment with erdafitinib, a tyrosine kinase inhibitor (TKI) prescribed on the basis of a compassionate-use program.

Methods: Analysis of anthropometric, biochemical, clinical, and radiographic data of patients with CNS tumors who revealed an unanticipated growth spurt with initiation of therapy with erdafitinib was performed retrospectively.

Feasibility, tolerability, and first experience of intracystic treatment with peginterferon alfa-2a in patients with cystic craniopharyngioma.

Background: Children with craniopharyngiomas (CPs) typically suffer from a life-long chronic disease. The younger the child, the more vulnerable the maturing brain is to invasive therapies such as surgery or radiotherapy. Therefore, treatment modalities facilitating avoidance or delay of invasive therapies are beneficial for these patients.

Platform trial design for neurofibromatosis type 1, NF2-related schwannomatosis and non-NF2-related schwannomatosis: A potential model for rare diseases.

Background: Neurofibromatosis type 1, -related schwannomatosis and non--related schwannomatosis (grouped under the abbreviation "NF") are rare hereditary tumor predisposition syndromes. Due to the low prevalence, variability in the range, and severity of manifestations, as well as limited treatment options, these conditions require innovative trial designs to accelerate the development of new treatments.

Methods: Within European Patient-Centric Clinical Trial Platforms (EU-PEARL), we designed 2 platform-basket trials in NF.

Resistance, rebound, and recurrence regrowth patterns in pediatric low-grade glioma treated by MAPK inhibition: A modified Delphi approach to build international consensus-based definitions-International Pediatric Low-Grade Glioma Coalition.

Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor group. The natural history, when curative resection is not possible, is one of a chronic disease with periods of tumor stability and episodes of tumor progression. While there is a high overall survival rate, many patients experience significant and potentially lifelong morbidities.

The telovelar approach for fourth ventricular tumors in children: is removal of the posterior arch of C1 necessary?

Purpose: Various surgical nuances of the telovelar approach have been suggested. The necessity of removing the posterior arch of C1 to accomplish optimal tumor exposure is still debated. Therefore, we report on our experience and technical details of the fourth ventricular tumor resection in a modified prone position without systematic removal of the posterior arch of C1.

Feasibility and antitumour activity of the FGFR inhibitor erdafitnib in three paediatric CNS tumour patients.

Alterations of the fibroblast growth factor (FGF) signalling pathway are increasingly recognized as frequent oncogenic drivers of paediatric brain tumours. We report on three patients treated with the selective FGFR1-4 inhibitor erdafitinib. Two patients were diagnosed with a posterior fossa ependymoma group A (PFA EPN) and one with a low-grade glioma (LGG), harbouring FGFR3/FGFR1 overexpression and an FGFR1 internal tandem duplication (ITD), respectively.

Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen: A Nonrandomized Controlled Trial.

Importance: Medulloblastoma recurrence in patients who have previously received irradiation has a dismal prognosis and lacks a standard salvage regimen.

Objective: To evaluate the response rate of pediatric patients with medulloblastoma recurrence using an antiangiogenic metronomic combinatorial approach (Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial [MEMMAT]).

Design, Setting, And Participants: This phase 2, investigator-initiated, multicenter nonrandomized controlled trial assessed 40 patients with relapsed or refractory medulloblastoma without a ventriculoperitoneal shunt who were younger than 20 years at original diagnosis.

Proof-of-Concept for Liquid Biopsy Disease Monitoring of -Amplified Group 3 Medulloblastoma by Droplet Digital PCR.

Background: Liquid biopsy diagnostic methods are an emerging complementary tool to imaging and pathology techniques across various cancer types. However, there is still no established method for the detection of molecular alterations and disease monitoring in MB, the most common malignant CNS tumor in the pediatric population. In the presented study, we investigated droplet digital polymerase chain reaction (ddPCR) as a highly sensitive method for the detection of amplification in bodily fluids of group 3 MB patients.

ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1.

Background: Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder, predisposing development of benign and malignant tumours. Given the oncogenic potential, long-term surveillance is important in patients with NF1. Proposals for NF1 care and its specific manifestations have been developed, but lack integration within routine care.

Constitutional Microsatellite Instability, Genotype, and Phenotype Correlations in Constitutional Mismatch Repair Deficiency.

Background & Aims: Constitutional mismatch repair deficiency (CMMRD) is a rare recessive childhood cancer predisposition syndrome caused by germline mismatch repair variants. Constitutional microsatellite instability (cMSI) is a CMMRD diagnostic hallmark and may associate with cancer risk. We quantified cMSI in a large CMMRD patient cohort to explore genotype-phenotype correlations using novel MSI markers selected for instability in blood.

Viral infections in pediatric brain tumor patients treated with targeted therapies.

Background: Brain tumors are the most common solid malignancies and the leading cause of cancer-related mortality in children. While numerous studies report on viral infections in children with hematologic malignancies and solid organ transplantation, epidemiologic data on the incidence and outcome of viral infections in pediatric patients with brain tumors treated with targeted therapies are still lacking.

Objectives/study Design: We retrospectively reviewed all children with brain tumors receiving targeted therapies in a primary or recurrent setting at the Medical University of Vienna from 2006 to 2021.

Prospective Evaluation of Kidney Function in Long-Term Survivors of Pediatric CNS Tumors.

Purpose: Numerous acute effects of chemotherapeutics on kidney function are well described. However, data on the long-term effects of chemotherapy in the growing population of childhood central nervous system (CNS) tumor survivors is limited. We aimed to evaluate the kidney function of a cohort of long-term CNS tumor survivors treated with different standard chemotherapeutic regimens.