Treatment of Medulloblastoma in the Adolescent and Young Adult Population: A Systematic Review.

Medulloblastoma is the most frequent high-grade tumor of the central nervous system in children but accounts for less than 1% of these tumors in adults. Adolescent and young adult (AYA) patients are between both age groups, and different approaches are used to treat medulloblastoma in this population. We performed a systematic review of studies published between 2007 and 2023 that reported treatment approaches and survival data of AYA patients with medulloblastoma, defined as 15 to 39 years of age at diagnosis.

Bridging the age gap: a review of molecularly informed treatments for glioma in adolescents and young adults.

Gliomas are the most common primary central nervous system (CNS) tumors and a major cause of cancer-related mortality in children (age <15 years), adolescents and young adults (AYA, ages 15-39 years), and adults (age >39 years). Molecular pathology has helped enhance the characterization of these tumors, revealing a heterogeneous and ever more complex group of malignancies. Recent molecular analyses have led to an increased appreciation of common genomic alterations prevalent across all ages.

Treatment of NF1-Associated Optic Pathway/Hypothalamic Gliomas in Patients With Diencephalic Syndrome.

Diencephalic syndrome is usually associated with tumors in the hypothalamic region, rarely occurring in patients with neurofibromatosis type 1 (NF1)-associated gliomas. We describe the clinical presentation and response to treatment in 3 patients with NF1 presenting with diencephalic syndrome as first symptom of optic pathway/hypothalamic glioma (OPHG). Because of the rarity of this constellation, knowledge about the clinical course and best treatment options for patients with NF1-associated OPHG and diencephalic syndrome is still limited.

Response and resistance to BRAF inhibition in gliomas: Roadblocks ahead?

BRAF represents the most common BRAF mutation in all human cancers. Among central nervous system (CNS) tumors, BRAF is mostly found in pediatric low-grade gliomas (pLGG, ~20%) and, less frequently, in pediatric high-grade gliomas (pHGG, 5-15%) and adult glioblastomas (GBM, ~5%). The integration of BRAF inhibitors (BRAFi) in the treatment of patients with gliomas brought a paradigm shift to clinical care.

Real-time drug testing of paediatric diffuse midline glioma to support clinical decision making: The Zurich DIPG/DMG centre experience.

Background: Children diagnosed with diffuse midline gliomas (DMG) have an extremely poor overall survival: 9-12 months from diagnosis with currently no curative treatment options. Given DMG molecular heterogeneity, surgical biopsies are needed for molecular profiling and as part of enrolment into molecular-based and precision medicine type clinical interventions. In this study, we describe the results of real time profiling and drug testing at the diffuse intrinsic pontine glioma/DMG Research Centre at University Children's Hospital Zurich.

The children's brain tumor network (CBTN) - Accelerating research in pediatric central nervous system tumors through collaboration and open science.

Pediatric brain tumors are the leading cause of cancer-related death in children in the United States and contribute a disproportionate number of potential years of life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary cancers. The Children's Brain Tumor Network (CBTN) is a multi-institutional international clinical research consortium created to advance therapeutic development through the collection and rapid distribution of biospecimens and data via open-science research platforms for real-time access and use by the global research community.

Educational Attainment and Employment Outcome of Survivors of Pediatric CNS Tumors in Switzerland-A Report from the Swiss Childhood Cancer Survivor Study.

Background: Childhood cancer survivors diagnosed with a central nervous system (CNS) tumor are at risk for educational and vocational challenges. This study compared educational attainment and employment outcome in survivors of CNS tumors to survivors of other malignancies.

Methods: The questionnaire-based Swiss Childhood Cancer Survivor Study (SCCSS) included cancer patients diagnosed between 1976 and 2010, aged ≤20 years, who survived ≥5 years after diagnosis.

Central nervous system tumors in children under 5 years of age: a report on treatment burden, survival and long-term outcomes.

Purpose: The challenges of treating central nervous system (CNS) tumors in young children are many. These include age-specific tumor characteristics, limited treatment options, and susceptibility of the developing CNS to cytotoxic therapy. The aim of this study was to analyze the long-term survival, health-related, and educational/occupational outcomes of this vulnerable patient population.

Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma.

Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation. Nearly all recurrent medulloblastomas and posterior fossa group A (PFA) ependymomas are located adjacent to and bathed by the cerebrospinal fluid, presenting an opportunity for locoregional therapy, bypassing the blood-brain barrier. We identify three cell-surface targets, EPHA2, HER2 and interleukin 13 receptor α2, expressed on medulloblastomas and ependymomas, but not expressed in the normal developing brain.

Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas.

Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of >1,000 clinically annotated pLGG. Eighty-four percent of cases harbored a driver alteration, while those without an identified alteration also often exhibited upregulation of the RAS/MAPK pathway.

Pediatric hemispheric high-grade glioma: targeting the future.

Pediatric high-grade gliomas (pHGGs) are a group of tumors affecting approximately 0.85 children per 100,000 annually. The general outcome for these tumors is poor with 5-year survival rates of less than 20%.

Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas.

Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups.

TGF-β Determines the Pro-migratory Potential of bFGF Signaling in Medulloblastoma.

The microenvironment shapes cell behavior and determines metastatic outcomes of tumors. We addressed how microenvironmental cues control tumor cell invasion in pediatric medulloblastoma (MB). We show that bFGF promotes MB tumor cell invasion through FGF receptor (FGFR) in vitro and that blockade of FGFR represses brain tissue infiltration in vivo.

Cerebellar tumors.

The cerebellum is the most common site of presentation of central nervous system tumors in children but exceedingly rare in adults. Children often present with acute symptoms related to increased intracranial pressure, requiring urgent surgical intervention. The differential diagnosis is broad and includes a variety of benign and malignant entities.

A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases.

While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninges. We present evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrate in vivo, through flank xenografting and parabiosis, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form leptomeningeal metastases.

Review of molecular classification and treatment implications of pediatric brain tumors.

Purpose Of Review: Brain tumors are the most common solid tumors and leading cause of cancer-related death in children. The advent of large-scale genomics has resulted in a plethora of profiling studies that have mapped the genetic and epigenetic landscapes of pediatric brain tumors, ringing in a new era of precision diagnostics and targeted therapies. In this review, we highlight the most recent findings, focusing on studies published after 2015, and discuss how new evidence is changing the care of children with brain tumors.

Multiplex Detection of Pediatric Low-Grade Glioma Signature Fusion Transcripts and Duplications Using the NanoString nCounter System.

Previous studies identified recurrent fusion and duplication events in pediatric low-grade glioma (pLGG). In addition to their role in diagnosis, the presence of these events aid in dictating therapy and predicting patient survival. Clinically, BRAF alterations are most commonly identified using fluorescent in situ hybridization (FISH).

Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510).