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).

Stratified Medicine Paediatrics: Cell free DNA and serial tumour sequencing identifies subtype specific cancer evolution and epigenetic states.

We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and paired plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tissue and cfDNA sequencing results were concordant, with a wider spectrum of mutant alleles and higher degree of intra-tumour heterogeneity captured by the latter, if sufficient circulating tumour-derived DNA (ctDNA) was present. Serial tumour sequencing identified putative drivers of relapse, with alterations in epigenetic drivers being a common feature.

The impact of fibre and prebiotic interventions on outcomes in cancer and haematopoietic stem cell transplantation: A systematic review.

Background & Aims: Cancer therapy is associated with a range of toxicities that severely impact patient well-being and a range of clinical outcomes. Dietary fibre/prebiotics characteristically improve the gastrointestinal microenvironment, which consequently elicits beneficial downstream effects that could be relevant to the prevention and management of treatment-related toxicities. Despite the compelling theoretical scientific rationale there has been limited effort to synthesise the available evidence to conclude such scientific underpinning to the clinical use of fibre/prebiotics in cancer patients.

Bi-modal confirmation of liposome delivery to the brain after focused ultrasound-induced blood-brain barrier opening.

Focused ultrasound-mediated opening of the blood-brain barrier offers a great opportunity to deliver therapeutics into hard-to-treat brain tumors such as glioblastoma multiforme or diffuse midline glioma. However, the potential of the technique to offer a time window for efficient nanomedicine delivery has not been thoroughly studied. Non-invasive and targeted delivery of large drug-loaded nanocarriers, such as liposomes, could offer a safe and scalable method of personalized therapy for the treatment of brain pathologies.

Treatment-related survival patterns in diffuse intrinsic pontine glioma using a historical cohort: A report from the European Society for Pediatric Oncology DIPG/DMG Registry.

Background: Our aim is to investigate the association of treatment with survival in patients with diffuse intrinsic pontine glioma (DIPG) by examining 6 historical treatment paths.

Methods: We retrospectively analyzed data from 409 patients with radiologically centrally reviewed DIPG, sourced from the German Society of Pediatric Oncology and Hematology HIT-HGG trial database and the SIOPE-DIPG/DMG Registry. Survival outcomes were estimated using the Kaplan-Meier method, and univariable and multivariable Cox proportional hazard models were estimated to study treatment effects.

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.

Experiences of families post treatment for childhood brain tumours during medical clinic consultations regarding health-related quality of life, unmet needs and communication barriers: A qualitative exploration.

Background: Many studies highlight poor health-related quality of life (HRQoL) in children treated for brain tumours and their parents. However, little is known about the extent to which their informational, healthcare and communication needs regarding HRQoL are met during medical outpatient consultations.

Aim: To explore the experiences of families regarding communication with physicians about HRQoL issues during consultations after treatment for childhood brain tumours.

Comments and Controversies in Oncology: The Tribulations of Trials Developing ONC201.

Our international team highlights issues with efficacy reports in several studies on DMG with the new drug ONC201.

Decision making for health-related research outcomes that alter diagnosis: A model from paediatric brain tumours.

Aims: The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro-oncology speciality.

The role of reoperation in pediatric cerebellar pilocytic astrocytoma.

Objective: Cerebellar pilocytic astrocytomas (cPAs) in childhood have long been recognized to have a good prognosis after total resection, but the outcome after incomplete resective surgery remains largely unpredictable, with the incidence of radiological progressive disease ranging from 18% to 100%. It has been traditionally thought that gross-total resection was required for long-term survival, and small residuals were classically resected in a subsequent operation.

Methods: The authors analyzed their pediatric low-grade glioma (PLGG) database for cases treated between 1985 and 2020 and filtered for intracranial PAs, to determine what clinical or radiological factors precipitated revisional resective surgery in their single quaternary care center cohort.

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.

Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.

Background: The term gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features could not be established.

Methods: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization.

Results: Median overall survival (OS) was 15.

Characterisation of paediatric brain tumours by their MRS metabolite profiles.

H-magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single-voxel MRS (point-resolved single-voxel spectroscopy sequence, 1.

Precision Medicine for Childhood Cancer: Current Limitations and Future Perspectives.

Greater collaboration needed to realize potential of molecular profiling initiatives for pediatric cancers.

Consensus framework for conducting phase I/II clinical trials for children, adolescents, and young adults with pediatric low-grade glioma: Guidelines established by the International Pediatric Low-Grade Glioma Coalition Clinical Trial Working Group.

Within the last few decades, we have witnessed tremendous advancements in the study of pediatric low-grade gliomas (pLGG), leading to a much-improved understanding of their molecular underpinnings. Consequently, we have achieved successful milestones in developing and implementing targeted therapeutic agents for treating these tumors. However, the community continues to face many unknowns when it comes to the most effective clinical implementation of these novel targeted inhibitors or combinations thereof.

A novel diagnostic method for a rare fungus: FcMBL facilitates identification in an immunocompromised neonate.

Fungemia negatively impacts patient outcomes, current diagnostics lack sensitivity to identify emerging rare mycoses, and fungal infections are increasing in prevalence, variety, and resistance. We report a case of in an immunocompromised neonate in which FcMBL bead-based matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) resulted in species identification roughly 30 hours before standard pathogen identification methods. Deploying FcMBL bead-based MALDI-TOF MS may improve the speed and accuracy of identification, and therefore treatment, of rare pathogens.

Dabrafenib plus Trametinib in Pediatric Glioma with V600 Mutations.

Background: Detection of the V600E mutation in pediatric low-grade glioma has been associated with a lower response to standard chemotherapy. In previous trials, dabrafenib (both as monotherapy and in combination with trametinib) has shown efficacy in recurrent pediatric low-grade glioma with V600 mutations, findings that warrant further evaluation of this combination as first-line therapy.

Methods: In this phase 2 trial, patients with pediatric low-grade glioma with V600 mutations who were scheduled to receive first-line therapy were randomly assigned in a 2:1 ratio to receive dabrafenib plus trametinib or standard chemotherapy (carboplatin plus vincristine).

Evaluating preclinical evidence for clinical translation in childhood brain tumours: Guidelines from the CONNECT, PNOC, and ITCC brain networks.

Clinical outcomes for many childhood brain tumours remain poor, despite our increasing understanding of the underlying disease biology. Advances in molecular diagnostics have refined our ability to classify tumour types and subtypes, and efforts are underway across multiple international paediatric neuro-oncology consortia to take novel biological insights in the worst prognosis entities into innovative clinical trials. Whilst for the first time we are designing such studies on the basis of disease-specific biological data, the levels of preclincial evidence in appropriate model systems on which these trials are initiated is still widely variable.

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.