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.

Vasospasm and subsequent stroke from paraneoplastic syndrome in a pediatric patient with an intracranial mature teratoma: a case report.

Teratomas account for 18-20% of all intracranial germ cell tumors and mostly occur in the pineal region with only a few cases of pediatric sellar and suprasellar teratomas described in the literature. Here, we present a case of a child with an intracranial mature teratoma with pancreatic features causing vasospasm and subsequent stroke, found to be positive for CDKN2A-an independent variant associated with malignancy and small vessel disease leading to stroke.

A therapeutically targetable positive feedback loop between lnc-HLX-2-7, HLX, and MYC that promotes group 3 medulloblastoma.

Recent studies suggest that long non-coding RNAs (lncRNAs) contribute to medulloblastoma (MB) formation and progression. We have identified an lncRNA, lnc-HLX-2-7, as a potential therapeutic target in group 3 (G3) MBs. lnc-HLX-2-7 RNA specifically accumulates in the promoter region of HLX, a sense-overlapping gene of lnc-HLX-2-7, which activates HLX expression by recruiting multiple factors, including enhancer elements.

miRNA-211 maintains metabolic homeostasis in medulloblastoma through its target gene long-chain acyl-CoA synthetase 4.

The prognosis of childhood medulloblastoma (MB) is often poor, and it usually requires aggressive therapy that adversely affects quality of life. microRNA-211 (miR-211) was previously identified as an important regulator of cells that descend from neural cells. Since medulloblastomas primarily affect cells with similar ontogeny, we investigated the role and mechanism of miR-211 in MB.

A Pilot Study Omitting Radiation in the Treatment of Children with Newly Diagnosed Wnt-Activated Medulloblastoma.

Purpose: Treatment of wingless (WNT)-activated medulloblastoma (WNT+MB) with surgery, irradiation (XRT), and chemotherapy results in excellent outcomes. We studied the efficacy of therapy de-intensification by omitting XRT entirely in children with WNT+MB.

Patients And Methods: Tumors were molecularly screened to confirm the diagnosis of WNT+MB.

A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial.

Background: Facial angiofibromas (FAs) are a major feature of tuberous sclerosis complex (TSC). Topical rapamycin can successfully treat FAs. A new stabilized cream formulation that protects rapamycin from oxidation has been developed in 0.

The oncogenic circular RNA circ_63706 is a potential therapeutic target in sonic hedgehog-subtype childhood medulloblastomas.

Medulloblastoma (MB) develops through various genetic, epigenetic, and non-coding (nc) RNA-related mechanisms, but the roles played by ncRNAs, particularly circular RNAs (circRNAs), remain poorly defined. CircRNAs are increasingly recognized as stable non-coding RNA therapeutic targets in many cancers, but little is known about their function in MBs. To determine medulloblastoma subgroup-specific circRNAs, publicly available RNA sequencing (RNA-seq) data from 175 MB patients were interrogated to identify circRNAs that differentiate between MB subgroups.

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.

The long non-coding RNA and its binding partner PTBP1 regulate exon 5 skipping of transcripts in group 4 medulloblastomas.

Background: Although some of the regulatory genes, signaling pathways, and gene regulatory networks altered in medulloblastomas (MB) are known, the roles of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), are poorly described. Here we report that the lncRNA () gene is upregulated in group 4 medulloblastoma (G4 MB).

Methods: expression was assessed in MB subgroup patient-derived xenografts, cell lines, and patient samples.

A phase I study of irinotecan and temozolomide with bevacizumab in children with recurrent/refractory central nervous system tumors.

Purpose: Children with relapsed/refractory central nervous system (CNS) tumors require novel combinations of therapies. Irinotecan and temozolomide (IT) is a frequently used therapy with an established toxicity profile. Bevacizumab is an anti-VEGF monoclonal antibody with demonstrated activity in CNS tumors.

Medulloblastoma cerebrospinal fluid reveals metabolites and lipids indicative of hypoxia and cancer-specific RNAs.

Medulloblastoma (MB) is the most common malignant brain tumor in children. There remains an unmet need for diagnostics to sensitively detect the disease, particularly recurrences. Cerebrospinal fluid (CSF) provides a window into the central nervous system, and liquid biopsy of CSF could provide a relatively non-invasive means for disease diagnosis.

Compassion fatigue in pediatric hematology, oncology, and bone marrow transplant healthcare providers: An integrative review.

Objective: Compassion fatigue (CF), which includes burnout and secondary traumatic stress, is highly prevalent among healthcare providers (HCPs). Ultimately, if left untreated, CF is often associated with absenteeism, decreased work performance, poor job satisfaction, and providers leaving their positions. To identify risk factors for developing CF and interventions to combat it in pediatric hematology, oncology, and bone marrow transplant (PHOB) HCPs.

The long noncoding RNA lnc-HLX-2-7 is oncogenic in Group 3 medulloblastomas.

Background: Medulloblastoma (MB) is an aggressive brain tumor that predominantly affects children. Recent high-throughput sequencing studies suggest that the noncoding RNA genome, in particular long noncoding RNAs (lncRNAs), contributes to MB subgrouping. Here we report the identification of a novel lncRNA, lnc-HLX-2-7, as a potential molecular marker and therapeutic target in Group 3 MBs.

The therapeutic and diagnostic potential of regulatory noncoding RNAs in medulloblastoma.

Medulloblastoma, a central nervous system tumor that predominantly affects children, always requires aggressive therapy. Nevertheless, it frequently recurs as resistant disease and is associated with high morbidity and mortality. While recent efforts to subclassify medulloblastoma based on molecular features have advanced our basic understanding of medulloblastoma pathogenesis, optimal targets to increase therapeutic efficacy and reduce side effects remain largely undefined.

Clinical characterization and long-term outcomes in pediatric epithelioid hemangioendothelioma.

There is a paucity of information about the clinical characteristics and long-term outcomes of pediatric epithelioid hemangioendothelioma (EHE), a rare vascular neoplasm commonly presenting in adulthood. In our case series of 24 patients with EHE aged 2-26 years, the majority presented with multi-organ disease. Progression was seen in 63% of patients with a mean time to progression of 18.

A Retrospective Review of the Use of Sirolimus for Pediatric Patients With Epithelioid Hemangioendothelioma.

Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor with no standardized treatment. The mammalian target of rapamycin inhibitor, sirolimus, has been used successfully in adult EHE and other vascular tumors in children but has not been studied in pediatric EHE. The aim of this retrospective case series is to discuss the results of sirolimus for treatment in 6 pediatric patients with EHE.

Body Mass Index at Pediatric Leukemia Diagnosis and the Risks of Relapse and Mortality: Findings from a Single Institution and Meta-analysis.

High body mass index (BMI) is associated with relapse of certain adult cancers, but limited knowledge exists on its association with pediatric leukemia relapse. We evaluated the association between overweight/obesity (BMI ≥ 85 percentile) at pediatric leukemia diagnosis and relapse or mortality. A meta-analysis combining our findings with those of previous studies was also performed.

Incidentally found brain tumors in the pediatric population: a case series and proposed treatment algorithm.

Purpose: With the increasing use of imaging, there has been an increase in the number of incidentally found brain lesions in pediatric patients resulting in a treatment dilemma for physicians and emotional strain for patients and families. Adult studies support initial surveillance of incidentally found low grade appearing lesions as the most appropriate approach. The aim of this study was to evaluate incidental lesions in the pediatric population and propose an initial treatment algorithm for such lesions.

Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma.

Pineoblastoma is a rare and highly aggressive brain cancer of childhood, histologically belonging to the spectrum of primitive neuroectodermal tumors. Patients with germline mutations in DICER1, a ribonuclease involved in microRNA processing, have increased risk of pineoblastoma, but genetic drivers of sporadic pineoblastoma remain unknown. Here, we analyzed pediatric and adult pineoblastoma samples (n = 23) using a combination of genome-wide DNA methylation profiling and whole-exome sequencing or whole-genome sequencing.