Pediatric-type diffuse low-grade gliomas with MYB alterations: Neuroimaging of the Diffuse astrocytomas, or -altered.

Background And Purpose: Diffuse astrocytoma, MYB or MYBL1-altered is a new tumor type in the family of Pediatric-type diffuse low-grade gliomas and genetically related to angiocentric glioma. Imaging features of Diffuse astrocytoma, MYB or MYBL1-altered are less well known. During our clinical work, we identified a relatively characteristic imaging pattern in a subset of our patients consisting of a large, diffuse hemispheric tumor with displaced central vessels which we termed the "fireworks sign".

Advancing CNS tumor diagnostics with expanded DNA methylation-based classification.

DNA methylation-based classification is integral to contemporary neuro-oncological diagnostics, as highlighted by the current World Health Organization (WHO) classification of central nervous system (CNS) tumors. We introduce the Heidelberg CNS Tumor Methylation Classifier version 12.8 (v12.

MSH2, MSH6, MLH1, and PMS2 immunohistochemistry as highly sensitive screening method for DNA mismatch repair deficiency syndromes in pediatric high-grade glioma.

Pediatric high-grade glioma (pedHGG) can occur as first manifestation of cancer predisposition syndromes resulting from pathogenic germline variants in the DNA mismatch repair (MMR) genes MSH2, MSH6, MLH1, and PMS2. The aim of this study was to establish a generalized screening for Lynch syndrome and constitutional MMR deficiency (CMMRD) in pedHGG patients, as the detection of MMR deficiencies (MMRD) may enable the upfront therapeutic use of checkpoint inhibitors and identification of variant carriers in the patients' families. We prospectively enrolled 155 centrally reviewed primary pedHGG patients for MMR-immunohistochemistry (IHC) as part of the HIT-HGG-2013 trial protocol.

VGLL fusions define a new class of intraparenchymal central nervous system schwannoma.

Background: Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the central nervous system (CNS). They are not classified as a separate tumor type in the 2021 World Health Organization classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly.

Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.

Methods: FIREFLY-1 investigated the efficacy (arm 1, n = 77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG).

DNA methylation-array interlaboratory comparison trial demonstrates highly reproducible paediatric CNS tumour classification across 13 international centres.

Aims: DNA methylation profiling, recently endorsed by the World Health Organisation (WHO) as a pivotal diagnostic tool for brain tumours, most commonly relies on bead arrays. Despite its widespread use, limited data exist on the technical reproducibility and potential cross-institutional differences. The LOGGIC Core BioClinical Data Bank registry conducted a prospective laboratory comparison trial with 12 international laboratories to enhance diagnostic accuracy for paediatric low-grade gliomas, focusing on technical aspects of DNA methylation data generation and profile interpretation under clinical real-time conditions.

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.

Adaption of neurosurgical resection patterns for pediatric low-grade glioma spanning two decades-Report from the German LGG-studies 1996-2018.

Introduction: Neurosurgery is considered the mainstay of treatment for pediatric low-grade glioma (LGG); the extent of resection determines subsequent stratification in current treatment protocols. Yet, surgical radicality must be balanced against the risks of complications that may affect long-term quality of life. We investigated whether this consideration impacted surgical resection patterns over time for patients of the German LGG studies.

Medulloblastoma in children with Fanconi anemia: Association with FA-D1/FA-N, SHH type and poor survival independent of treatment strategies.

Background: The outcome of children with medulloblastoma (MB) and Fanconi Anemia (FA), an inherited DNA repair deficiency, has not been described systematically. Treatment is complicated by high vulnerability to treatment-associated side effects, yet structured data are lacking. This study aims to give a comprehensive overview of clinical and molecular characteristics of pediatric FA MB patients.

Surgical options of chiasmatic hypothalamic glioma-a relevant part of therapy in an interdisciplinary approach for tumor control.

Objective: The extent of resection of pediatric low-grade glioma mostly improves progression-free survival. In chiasmatic hypothalamic glioma (CHG), complete resections are limited due to the relevantly high risk of associated neurological and endocrinological deficits. Still, surgery might have its role in the framework of a multidisciplinary team (MDT) approach.

Rapid DNA methylation-based classification of pediatric brain tumors from ultrasonic aspirate specimens.

Background: Although cavitating ultrasonic aspirators are commonly used in neurosurgical procedures, the suitability of ultrasonic aspirator-derived tumor material for diagnostic procedures is still controversial. Here, we explore the feasibility of using ultrasonic aspirator-resected tumor tissue to classify otherwise discarded sample material by fast DNA methylation-based analysis using low pass nanopore whole genome sequencing.

Methods: Ultrasonic aspirator-derived specimens from pediatric patients undergoing brain tumor resection were subjected to low-pass nanopore whole genome sequencing.

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.

Analysis of bihemispheric language function in pediatric neurosurgical patients using repetitive navigated transcranial magnetic stimulation.

Objective: Language dominance in the developing brain can vary widely across anatomical and pathological conditions as well as age groups. Repetitive navigated transcranial magnetic stimulation (rnTMS) has been applied to calculate the hemispheric dominance ratio (HDR) in adults. In this study, the authors aimed to assess the feasibility of using rnTMS to identify language lateralization in a pediatric neurosurgical cohort and to correlate the preoperative rnTMS findings with the postoperative language outcome.

The Supraorbital Eyebrow Approach in Pediatric Neurosurgery: Perspectives and Challenges of Frontal Keyhole Surgery.

Object: Supraorbital craniotomy via an eyebrow incision provides minimally invasive cosmetically favorable access to both orbital and intracranial pathologies. We describe the indication, surgical technique, and clinical course using this surgical approach in a cohort of patients from a single pediatric neurosurgery unit.

Methods: In a retrospective analysis, we identified all surgical cases between January 2013 and April 2022 who underwent the supraorbital craniotomy via an eyebrow incision.

Atypical language organization following perinatal infarctions of the left hemisphere is associated with structural changes in right-hemispheric grey matter.

Aim: To assess how atypical language organization after early left-hemispheric brain lesions affects grey matter in the contralesional hemisphere.

Method: This was a cross-sectional study with between-group comparisons of 14 patients (six female, 8-26 years) with perinatal left-hemispheric brain lesions (two arterial ischemic strokes, 11 periventricular haemorrhagic infarctions, one without classification) and 14 typically developing age-matched controls (TDC) with functional magnetic resonance imaging (fMRI) documented left-hemispheric language organization (six female, 8-28 years). MRI data were analysed with SPM12, CAT12, and custom scripts.

MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas.

Pediatric low-grade gliomas (pLGG) show heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. Thus, more complex stratification biomarkers are needed to identify patients likely to benefit from MAPKi therapy. Here, we identify MAPK-related genes enriched in MAPKi-sensitive cell lines using the GDSC dataset and apply them to calculate class-specific MAPKi sensitivity scores (MSSs) via single-sample gene set enrichment analysis.

Biopsies of Caudal Brainstem Tumors in Pediatric Patients-A Single-Center Retrospective Case Series.

Objective: The indication for performing biopsies in patients with diffuse lesions in the brain stem is controversial. The possible risks associated with the technically challenging interventions must be balanced against clarifying the diagnosis and the possible therapeutic options. We reviewed the feasibility, risk profile, and diagnostic yield of different biopsy techniques in a pediatric cohort.

Neurosurgical morbidity in pediatric supratentorial midline low-grade glioma: Results from the German LGG studies.

Surgical resection is a mainstay of treatment for pediatric low-grade glioma (LGG) within all current therapy algorithms, yet associated morbidity is scarcely reported. As supratentorial midline (SML) interventions are particularly challenging, we investigated the frequency of neurosurgical complications/new impairments aiming to identify their risk factors. Records were retrospectively analyzed from 318 patients with SML-LGG from successive German multicenter LGG studies, undergoing surgery between May 1998 and June 2020.

LOGGIC Core BioClinical Data Bank: Added clinical value of RNA-Seq in an international molecular diagnostic registry for pediatric low-grade glioma patients.

Background: The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data to support treatment decisions and interventional trial participation. Hence, the question arises whether implementation of RNA sequencing (RNA-Seq) using fresh frozen (FrFr) tumor tissue in addition to gene panel and DNA methylation analysis improves diagnostic accuracy and provides additional clinical benefit.

Methods: Analysis of patients aged 0 to 21 years, enrolled in Germany between April 2019 and February 2021, and for whom FrFr tissue was available.