ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma.

Purpose: Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults.

Methods: ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m twice daily, maximum 4 mg twice daily), regardless of food intake, in 3 weeks on/1 week off 28-day cycles.

A critical assessment of using ChatGPT for extracting structured data from clinical notes.

Existing natural language processing (NLP) methods to convert free-text clinical notes into structured data often require problem-specific annotations and model training. This study aims to evaluate ChatGPT's capacity to extract information from free-text medical notes efficiently and comprehensively. We developed a large language model (LLM)-based workflow, utilizing systems engineering methodology and spiral "prompt engineering" process, leveraging OpenAI's API for batch querying ChatGPT.

Osteosarcoma Explorer: A Data Commons With Clinical, Genomic, Protein, and Tissue Imaging Data for Osteosarcoma Research.

Purpose: Osteosarcoma research advancement requires enhanced data integration across different modalities and sources. Current osteosarcoma research, encompassing clinical, genomic, protein, and tissue imaging data, is hindered by the siloed landscape of data generation and storage.

Materials And Methods: Clinical, molecular profiling, and tissue imaging data for 573 patients with pediatric osteosarcoma were collected from four public and institutional sources.

Comprehensive characterization of patient-derived xenograft models of pediatric leukemia.

Patient-derived xenografts (PDX) remain valuable models for understanding the biology and for developing novel therapeutics. To expand current PDX models of childhood leukemia, we have developed new PDX models from Hispanic patients, a subgroup with a poorer overall outcome. Of 117 primary leukemia samples obtained, successful engraftment and serial passage in mice were achieved in 82 samples (70%).

Phase II study of everolimus for recurrent or progressive pediatric ependymoma.

Background: Preclinical studies have suggested that mTOR pathway signaling may be a potential therapeutic target for childhood ependymoma.

Methods: A phase II clinical trial (ClinicalTrials.gov identifier: NCT02155920) of single-agent everolimus was performed to test the hypothesis that mTOR pathway inhibition would result in tumor responses for children with recurrent and/or progressive ependymomas.

COVID-19 in people with neurofibromatosis 1, neurofibromatosis 2, or schwannomatosis.

Purpose: People with pre-existing conditions may be more susceptible to severe COVID-19 when infected by SARS-CoV-2. The relative risk and severity of SARS-CoV-2 infection in people with rare diseases such as neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), or schwannomatosis (SWN) is unknown.

Methods: We investigated the proportions of people with NF1, NF2, or SWN in the National COVID Cohort Collaborative (N3C) electronic health record data set who had a positive test result for SARS-CoV-2 or COVID-19.

MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.

The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 have made it the first medical therapy approved for this indication in the United States, the European Union, and elsewhere.

Targeted Therapies for the Neurofibromatoses.

Over the past several years, management of the tumors associated with the neurofibromatoses has been recognized to often require approaches that are distinct from their spontaneous counterparts. Focus has shifted to therapy aimed at minimizing symptoms given the risks of persistent, multiple tumors and new tumor growth. In this review, we will highlight the translation of preclinical data to therapeutic trials for patients with neurofibromatosis, particularly neurofibromatosis type 1 and neurofibromatosis type 2.

Insights into the Pathogenesis of NF1-Associated Neoplasms.

Neurofibromatosis type 1 (NF1) is one of the most common neurocutaneous genetic disorders, presenting with different cutaneous features such as café-au-lait macules, intertriginous skin freckling, and neurofibromas. Although most of the disease manifestations are benign, patients are at risk for a variety of malignancies, including malignant transformation of plexiform neurofibromas. Numerous studies have investigated the mechanisms by which these characteristic neurofibromas develop, with progress made toward unraveling the various players involved in their complex pathogenesis.

Recent progress in the treatment of cancer in children.

Although significant improvements have been made in the outcomes of children with cancer, the pace of improvement has slowed in recent years as the limits of therapy intensification may have been reached for many pediatric cancers. Furthermore, with increasing numbers of pediatric cancer survivors, the long-term side effects of treatment have become increasingly apparent. Therefore, attention has shifted to the use of molecularly targeted agents and immunotherapies to improve the outcomes of children who are not cured by traditional cytotoxic chemotherapies and to decrease exposure to cytotoxic chemotherapy and reduce late effects.

Risk Factors for Bullying Victimization in Children with Neurofibromatosis Type 1 (NF1).

Neurofibromatosis type 1 (NF1) is an autosomal disorder associated with numerous physical stigmata. Children with NF1 are at known risk for attention-deficit/hyperactivity disorder (ADHD), academic struggles, and significant social difficulties and adverse social outcomes, including bullying victimization. The primary aim of this study was to identify risk factors associated with bullying victimization in children with NF1 to better inform clinicians regarding targets for prevention and clinical intervention.

Margin-Free Fractionated Stereotactic Radiation Therapy for Pediatric Brain Tumors.

Purpose: Conventional radiation therapy (RT) to pediatric brain tumors exposes a large volume of normal brain to unwarranted radiation causing late toxicity. We hypothesized that in well demarcated pediatric tumors lacking microscopic extensions, fractionated stereotactic RT (SRT), without target volume expansions, can reduce high dose normal tissue irradiation without affecting local control.

Methods And Materials: Between 2008 and 2017, 52 pediatric patients with brain tumors were treated using the CyberKnife (CK) with SRT in 180 to 200 cGy per fraction.

The Use of MEK Inhibitors in Neurofibromatosis Type 1-Associated Tumors and Management of Toxicities.

Early-phase clinical trials using oral inhibitors of MEK, the mitogen-activated protein kinase kinase, have demonstrated benefit for patients with neurofibromatosis type 1 (NF1)-associated tumors, particularly progressive low-grade gliomas and plexiform neurofibromas. Given this potential of MEK inhibition as an effective medical therapy, the use of targeted agents in the NF1 population is likely to increase substantially. For clinicians with limited experience prescribing MEK inhibitors, concern about managing these treatments may be a barrier to use.

CT and MRI findings in leptomeningeal melanocytosis.

Leptomeningeal melanocytosis is a rare cause of seizure in the pediatric population. Shown here is a case of this disease in a 9-year-old male who presented with seizures and minor trauma. Imaging showed progression of leptomeningeal enhancement in the setting of increased seizure activity, and biopsy confirmed the diagnosis.

Cognition, ADHD Symptoms, and Functional Impairment in Children and Adolescents With Neurofibromatosis Type 1.

We examined the contribution of attention and executive cognitive processes to ADHD symptomatology in NF1, as well as the relationships between cognition and ADHD symptoms with functional outcomes. The study sample consisted of 141 children and adolescents with NF1. Children were administered neuropsychological tests that assessed attention and executive function, from which latent cognitive variables were derived.

Reproducibility of cognitive endpoints in clinical trials: lessons from neurofibromatosis type 1.

Objective: Rapid developments in understanding the molecular mechanisms underlying cognitive deficits in neurodevelopmental disorders have increased expectations for targeted, mechanism-based treatments. However, translation from preclinical models to human clinical trials has proven challenging. Poor reproducibility of cognitive endpoints may provide one explanation for this finding.

Rate and frequency of bullying victimization in school-age children with neurofibromatosis type 1 (NF1).

Children and adolescents with the genetic, tumor predisposition syndrome neurofibromatosis type I (NF1) have varying degrees of physical stigmata characteristic of the disease and experience high rates of social difficulties. The present study was the first to formally examine the rate (i.e.

Long-Term Effects of Bevacizumab on Vestibular Schwannoma Volume in Neurofibromatosis Type 2 Patients.

 Bevacizumab offers a medical treatment that may slow the growth of vestibular schwannomas (VS) and possibly preserve hearing in patients with neurofibromatosis type 2 (NF2). This study aims to investigate the effect of long-term bevacizumab treatment on VS progression.  Demographic, clinical, audiometric, and radiographic data were collected from the medical records of NF2 patients treated with bevacizumab at a tertiary medical center.

Metabolic syndrome is a sequela of radiation exposure in hypothalamic obesity among survivors of childhood brain tumors.

Survivors of childhood brain tumors may be at risk for early onset of metabolic syndrome, possibly secondary to surgery and/or radiation exposure. This study examines effects of radiation exposure to hypothalamus-pituitary-adrenal axis (HPA) on metabolic risk among survivors of childhood brain tumors. One hundred forty-two met inclusion criteria; 60 had tumor surgery plus radiation exposure (1 Gray (Gy)) to HPA.

Targeted MAPK Pathway Inhibitors in Patients With Disseminated Pilocytic Astrocytomas.

This report presents a series of 5 pediatric patients with disseminated pilocytic astrocytomas and frequent nonfusion activating mutations. Genetic variants in these patients' tumors include BRAF p.Val600Glu, BRAF p.

Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1.

Objective: To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1).

Methods: A multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8-15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70).