Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Designing a Time-Dependent Therapeutic Strategy using CDK4/6 Inhibitors in an Intracranial ATRT Model.

Background: Inhibitors targeting cyclin-dependent kinases 4 and 6 (CDK4/6), crucial for cell cycle regulation, have shown promise in early-stage studies for treating central nervous system (CNS) tumors. However, challenges such as limited CNS penetration, optimal treatment duration, and systemic side effects have impeded their clinical translation for pediatric brain tumors (PBTs).

Methods: We evaluated the potency of CDK4/6 inhibitors across various PBTs cell lines, focusing particularly on palbociclib against atypical teratoid rhabdoid tumor (ATRT) with cell viability assays and gene expression analysis.

Phase 2 Trial of Veliparib, Local Irradiation and Temozolomide in Patients with Newly Diagnosed High-Grade Glioma: A Children's Oncology Group Study.

Background: The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral poly(adenosine diphosphate-ribose) polymerase (PARP) 1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy.

Methods: We conducted a single-arm, non-randomized phase 2 clinical trial to determine whether treatment with veliparib and radiotherapy, followed by veliparib and temozolomide, improves progression-free survival in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations compared to patient level data from historical cohorts with closely matching clinical and molecular features.

Theranostic Intratumoral Convection-Enhanced Delivery of I-Omburtamab in Patients with Diffuse Intrinsic Pontine Glioma: Pharmacokinetics and Lesion Dosimetry.

Diffuse intrinsic pontine glioma (DIPG) is a rare childhood malignancy with poor prognosis. There are no effective treatment options other than external beam therapy. We conducted a pilot, first-in-human study using I-omburtamab imaging and theranostics as a therapeutic approach using a localized convection-enhanced delivery (CED) technique for administering radiolabeled antibody.

Laser interstitial thermal therapy as a radiation-sparing approach for central nervous system tumors in children with cancer predisposition syndromes: report of a child with Li-Fraumeni syndrome. Illustrative case.

Background: Ionizing radiation and alkylating chemotherapies increase secondary malignancy risk in patients with cancer predisposition syndromes (CPSs), such as Li-Fraumeni syndrome. Laser interstitial thermal therapy (LITT) is a minimally invasive ablation technique that has not been associated with mutagenic risks. We describe the case of a child with LFS and a history of treated choroid plexus carcinoma (CPC) who developed a second primary glial tumor that was safely treated with magnetic resonance imaging (MRI)-guided LITT.

The Role of Virtual Surgical Planning in Surgery for Complex Craniosynostosis.

Background: Virtual surgical planning (VSP) decreases reliance on intraoperative subjective assessment of aesthetic and functional outcomes in craniofacial surgery. Here, we describe our experience of using VSP for complex craniosynostosis surgery to inform preoperative decision making and optimize postoperative outcomes.

Methods: Chart review was performed for children treated with craniosynostosis at our institution from 2015 to 2021.

Diffuse Midline Gliomas: Challenges and New Strategies in a Changing Clinical Landscape.

Diffuse intrinsic pontine glioma (DIPG) was first described by Harvey Cushing, the father of modern neurosurgery, a century ago. Since then, the classification of this tumor changed significantly, as it is now part of the broader family of diffuse midline gliomas (DMGs), a heterogeneous group of tumors of midline structures encompassing the entire rostro-caudal space, from the thalamus to the spinal cord. DMGs are characterized by various epigenetic events that lead to chromatin remodeling similarities, as two decades of studies made possible by increased tissue availability showed.

Central nervous system tuberculoma mimicking a brain tumor: A case report.

The central nervous system (CNS) is a rare but serious site of tuberculosis spread that manifests in three forms: meningitis, spinal arachnoiditis, and CNS tuberculoma. CNS tuberculoma, or intracranial tuberculous granuloma, is a caseating or non-caseating granulomatous reaction within the brain parenchyma that may mimic a brain tumor. We present the case of a 10-year-old male patient with a travel history to Western Africa who presented to our institution after his fourth tonic-clonic seizure over 2 months.

The Future of Neuroendoscopy: Looking Ahead Through a Lens.

Neuroendoscopy has progressed remarkably in the past few decades. Ventriculoscopy, skull base endoscopy, and spinal endoscopy are now part of routine practice in the neurosurgical treatment of numerous pathologies. Like other developing fields, however, it faces numerous challenges and obstacles that must be overcome for the field to continue to evolve and expand.

Neuroendoscopy: The State of the Art.

Over the past century, neuroendoscopy developed into a mainstay of neurosurgical practice, allowing for minimally invasive approaches to the ventricles, skull base, and spine. Its development, however, is far from over. Current challenges are inherent in the very feature that renders neuroendoscopy appealing-the small channels of the modern endoscope allow surgery to be performed with minimal tissue retraction, but they also make hemostasis and resection of large masses difficult.

Neuroendoscopy: How We Got Here.

From its inception in ancient Egyptian rituals, neuroendoscopy always promised a minimally invasive route to the cerebrum. Early visionaries, however, hit the proverbial wall of technical development until the 20th century, when new technologies allowed for light to be transmitted across a tube for visualization of intracranial structures. Despite a hiccupping start, with surgical microscopy hampering initial excitement, the development and transformation of neuroendoscopy continued, and today it is a widespread and reliable surgical option for the treatment of numerous varied and complex pathologies.

Influence of focused ultrasound on locoregional drug delivery to the brain: Potential implications for brain tumor therapy.

Introduction: Efficient delivery of therapeutics across the blood-brain barrier (BBB) for the treatment of central nervous system (CNS) tumors is a major challenge to the development of safe and efficacious therapies. Locoregional drug delivery platforms offer an improved therapeutic index by achieving high drug concentrations in the target tissue with negligible systemic exposure. Intrathecal (intraventricular) [IT] and convection-enhanced delivery [CED] are two clinically relevant methods being employed for various CNS malignancies.

The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer.

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for rearrangement but harboring a p.

Comparative Analysis of 2D and 3D Metrics for Evaluation of Postoperative Outcomes Following Endoscopic Suturectomy for Sagittal Craniosynostosis.

To assess whether 3-dimensional (3D) volumetrics can be used to track and evaluate postoperative course of patients treated with endoscopic suturectomy for nonsyndromic sagittal synostosis, we compared changes in 2-dimensional (2D) measurements along with 3D volumetric correlates throughout the period of helmet therapy. Forty-six patients treated at our institution with endoscopic suturectomy for sagittal synostosis were retrospectively reviewed. Head circumference (HC), cephalic index (CI), and total cranial volumes (TCVs) were measured at 3 timepoints following surgery using optical surface scans obtained for helmet orthotics.

Fifty years of DIPG: looking at the future with hope.

Diffuse intrinsic pontine glioma (DIPG) is a primary brainstem tumor of childhood that carries a dismal prognosis, with median survival of less than 1 year. Because of the brain stem location and pattern of growth within the pons, Dr. Harvey Cushing, the father of modern neurosurgery, urged surgical abandonment.

Predictors of extent of resection and recurrence following endoscopic endonasal resection of craniopharyngioma.

Objective: Craniopharyngioma is a benign but surgically challenging brain tumor. Controversies exist regarding its ideal treatment strategy, goals of surgery, efficacy of radiation, and the long-term outcomes of these decisions. The authors of this study performed a detailed analysis of factors predictive of the extent of resection and recurrence in large series of craniopharyngiomas removed via an endoscopic endonasal approach (EEA) with long-term follow-up.

Preclinical validation of a novel therapeutic strategy for choroid plexus carcinoma.

Choroid plexus carcinoma (CPC) is a rare infantile brain tumor with an aggressive clinical course that often leaves children with debilitating side effects due to aggressive and toxic chemotherapies. Development of novel therapeutical strategies for this disease have been extremely limited owing to the rarity of the disease and the paucity of biologically relevant substrates. We conducted the first high-throughput screen (HTS) on a human patient-derived CPC cell line (Children Cancer Hospital Egypt, CCHE-45) and identified 427 top hits highlighting key molecular targets in CPC.

Leptomeningeal dissemination in pediatric brain tumors.

Leptomeningeal disease (LMD) in pediatric brain tumors (PBTs) is a poorly understood and categorized phenomenon. LMD incidence rates, as well as diagnosis, treatment, and screening practices, vary greatly depending on the primary tumor pathology. While LMD is encountered most frequently in medulloblastoma, reports of LMD have been described across a wide variety of PBT pathologies.

Treatment of Pediatric Low-Grade Gliomas.

Purpose Of Review: Pediatric low-grade gliomas and glioneuronal tumors (pLGG) account for approximately 30% of pediatric CNS neoplasms, encompassing a heterogeneous group of tumors of primarily glial or mixed neuronal-glial histology. This article reviews the treatment of pLGG with emphasis on an individualized approach incorporating multidisciplinary input from surgery, radiation oncology, neuroradiology, neuropathology, and pediatric oncology to carefully weigh the risks and benefits of specific interventions against tumor-related morbidity. Complete surgical resection can be curative for cerebellar and hemispheric lesions, while use of radiotherapy is restricted to older patients or those refractory to medical therapy.

Durability of an endoscopic management strategy for recurrent choroid plexus carcinoma with a comprehensive molecular characterization: illustrative case.

Objective: Choroid plexus carcinoma (CPC) is a rare, primarily intraventricular neoplasm. Extent of resection correlates with improved outcomes but is limited due to tumor vascularity and size. Evidence on optimal surgical management and molecular drivers of recurrence remains limited.

Outcomes of intraventricular 131-I-omburtamab and external beam radiotherapy in patients with recurrent medulloblastoma and ependymoma.

Purpose: Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space. These patients often previously received external beam radiotherapy (EBRT) to a portion or full craniospinal axis (CSI) as part of upfront therapy. Little is known regarding outcomes after re-irradiation as part of multimodality therapy including cRIT.

Defining Occult High-Risk Cysts of the Pineal Region: A Case Series.

Background: Absence of hydrocephalus on neuroimaging may impart a false sense of security for patients with pineal cysts. In this case series, we characterize a subset of patients with pineal cysts having an occult presentation. Unifying features of worsening paroxysmal headaches suggesting intermittent obstructive hydrocephalus and radiographic evidence of third ventricular invagination characterize these patients as high risk.