Pediatric brain cancer

BACKGROUND: Ependymomas are the third most common brain cancer in children and have no targeted therapies. They are divided into at least 9 major subtypes based on molecular characteristics and major drivers and have few genetic mutations compared to the adult form of this disease, leading to investigation of other mechanisms. SUMMARY: Epigenetic alterations such as transcriptional programs activated by oncofusion proteins and alterations in histone modifications play an important role in development of this disease...

Pediatric high-grade gliomas (pHGG) are a rare yet devastating malignancy of the central nervous system's glial support cells, affecting children, adolescents, and young adults. Tumors of the central nervous system account for the leading cause of pediatric mortality of which high-grade gliomas present a significantly grim prognosis. While the past few decades have seen many pediatric cancers experiencing significant improvements in overall survival, the prospect of survival for patients diagnosed with pHGGs has conversely remained unchanged...

Pediatric high-grade glioma (pHGG) including pediatric glioblastoma (pGBM) are highly aggressive pediatric central nervous system (CNS) malignancies. pGBM comprises approximately 3% of all pediatric CNS malignancies and has a 5-year survival rate of approximately 20%. Surgical resection and chemoradiation are often the standard of care for pGBM and pHGG, however, even with these interventions, survival for children diagnosed with pGBM and pHGG remains poor. Due to shortcomings associated with the standard of care, many efforts have been made to create novel immunotherapeutic approaches targeted to these malignancies...

Human leukocyte antigen (HLA) restriction of conventional T-cell targeting introduces complexity in generating T-cell therapy strategies for patients with cancer with diverse HLA-backgrounds. A subpopulation of atypical, major histocompatibility complex-I related protein 1 (MR1)-restricted T-cells, distinctive from mucosal-associated invariant T-cells (MAITs), was recently identified recognizing currently unidentified MR1-presented cancer-specific metabolites. It is hypothesized that the MC.7.G5 MR1T-clone has potential as a pan-cancer, pan-population T-cell immunotherapy approach...

PURPOSE: Somatic molecular profiling of pediatric brain tumors aids with the diagnosis and treatment of patients with a variety of high- and low-grade central nervous system neoplasms. Here, we report follow-up targeted germline evaluation for patients with possible germline variants following tumor only testing in the initial year in which somatic molecular testing was implemented at a single institution. PATIENTS AND METHODS: Somatic testing was completed for all tumors of the central nervous system (CNS) undergoing diagnostic workup at Seattle Children's Hospital during the study period of November 2015 to November 2016...

OBJECTIVE: Brain tumors are a global problem, leading to higher cancer-related morbidity and mortality rates in children. Despite the progressive though slow advances in neuro-oncology care, research, and diagnostics in sub-Saharan Africa (SSA), the epidemiological landscape of pediatric brain tumors (PBTs) remains underestimated. This study aimed to systematically analyze the distribution of PBT types in SSA. METHODS: Ovid Medline, Global Index Medicus, African Journals Online, Google Scholar, and faculty of medicine libraries were searched for literature on PBTs in SSA published before October 29, 2022...

UNLABELLED: Medulloblastoma is one of the most common malignant brain tumors of children, and 30% of medulloblastomas are driven by gain-of-function genetic lesions in the Sonic Hedgehog (SHH) signaling pathway. EYA1, a haloacid dehalogenase phosphatase and transcription factor, is critical for tumorigenesis and proliferation of SHH medulloblastoma (SHH-MB). Benzarone and benzbromarone have been identified as allosteric inhibitors of EYA proteins. Using benzarone as a point of departure, we developed a panel of 35 derivatives and tested them in SHH-MB...

Proton therapy is a promising modality for craniospinal irradiation (CSI), offering dosimetric advantages over conventional treatments. While significant attention has been paid to spine fields, for the brain fields, only dose reduction to the lens of the eye has been reported. Hence, the objective of this study is to assess the potential gains and feasibility of adopting different treatment planning techniques for the entire brain within the CSI target. To this end, eight previously treated CSI patients underwent retrospective replanning using various techniques: (1) intensity modulated proton therapy (IMPT) optimization, (2) the modification/addition of field directions, and (3) the pre-optimization removal of superficially placed spots...

BACKGROUND/OBJECTIVES: Survivors of pediatric brain tumors (SPBT) experience significant social challenges, including fewer friends and greater isolation than peers. Difficulties in face processing and visual social attention have been implicated in these outcomes. This study evaluated facial expression recognition (FER), social attention, and their associations with social impairments in SPBT. METHODS: SPBT (N = 54; ages 7-16) at least 2 years post treatment completed a measure of FER, while parents completed measures of social impairment...

Ependymomas are rare brain tumors that can occur in both children and adults. Subdivided by the tumors' initial location, ependymomas develop in the central nervous system in the supratentorial or infratentorial/posterior fossa region, or the spinal cord. Supratentorial ependymomas (ST-EPNs) are predominantly characterized by common driver gene fusions such as ZFTA and YAP1 fusions. Some variants of ST-EPNs carry a high overall survival rate. In poorly responding ST-EPN variants, high levels of inter- and intratumoral heterogeneity, limited therapeutic strategies, and tumor recurrence are among the reasons for poor patient outcomes with other ST-EPN subtypes...

BACKGROUND: Optic pathway gliomas (OPG) represent 5% of childhood brain tumors. Successive relapses lead to multiple treatments exposing to late complications. METHODS: We included patients treated at Gustave Roussy (GR) between 01.1980 and 12.2015 for OPG, before 18 years-old and alive at 5 years from diagnosis. Mortality and physical health conditions data were extracted from medical data files and updated thanks to the GR long-term follow-up program and French national mortality registry for patients included in the French Childhood Cancer Survivor Study...

BACKGROUND: Children with cancer receiving chemotherapy commonly report a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. The role of the gut microbiome and its functional metabolites in PNS is rarely studied among children with cancer. This study investigated the associations between the gut microbiome-metabolome pathways and PNS in children with cancer across chemotherapy as compared to healthy children. METHODS: A case-control study was conducted...

BACKGROUND: To investigate clinical characteristics, prognoses, and impacts of treatments on prognoses of neuroblastoma patients with bone or liver metastasis. METHODS: This retrospective cohort study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database 2010-2019. The outcomes were 3-year cancer-specific survival (CSS) and 5-year CSS. Multivariable COX risk proportional models were established to assess the association between metastasis types and CSS...

The cumulative incidence of secondary cancers in childhood cancer survivors at 20 years after treatment is 2-5%, which is 3-20 times higher than in the general population. Risk factors include radiation therapy, alkylating agents, platinum drugs, and topoisomerase Ⅱ inhibitors. A retrospective cohort study of 15 pediatric oncology hospitals in Japan revealed that the time to development of a second cancer varies from 5 years or less for hematologic tumors, 10 years or less for bone/soft tissue tumors, approximately 10 years for brain tumors, and 15-20 years for thyroid and adult-type cancers...

Five-year glioblastoma (GBM) survivors (LTS) are the minority of the isocitrate dehydrogenase (IDH)-wild-type GBM patients, and their molecular fingerprint is still largely unexplored. This multicenter retrospective study analyzed a large LTS-GBM cohort from nine Italian institutions and molecularly characterized a subgroup of patients by mutation, DNA methylation (DNAm) and copy number variation (CNV) profiling, comparing it to standard survival GBM. Mutation scan allowed the identification of pathogenic variants in most cases, showing a similar mutational spectrum in both groups, and highlighted TP53 as the most commonly mutated gene in the LTS group...

BACKGROUND: Unusual olfactory perception, often referred to as "phantosmia" or "cacosmia" has been reported during brain radiotherapy (RT), but is infrequent and does not typically interfere with the ability to deliver treatment. We seek to determine the rate of phantosmia for patients treated with proton craniospinal irradiation (CSI) and identify any potential clinical or treatment-related associations. METHODS: We performed a retrospective review of 127 pediatric patients treated with CSI, followed by a boost to the brain for primary brain tumors in a single institution between 2016 and 2021...

Neuroblastoma is the most common extracranial malignant tumor of childhood, accounting for 15% of all pediatric cancer deaths. Despite significant advances in our understanding of neuroblastoma biology, five-year survival rates for high-risk disease remain less than 50%, highlighting the importance of identifying novel therapeutic targets to combat the disease. MYCN amplification is the most frequent and predictive molecular aberration correlating with poor outcome in neuroblastoma. N-Myc is a short-lived protein primarily due to its rapid proteasomal degradation, a potentially exploitable vulnerability in neuroblastoma...

Children with neurologic disorders face increased risks for mental health and neurodevelopmental conditions, with information often limited to parent report. To better understand mental health and neurodevelopmental needs in this population, a retrospective chart review of a convenience sample of children with neurologic disorders referred for a neuropsychological evaluation was conducted in the present study to explore interrater agreement between care team members (referring providers, parents, pediatric neuropsychologist)...

ALA PDT, first approved as a topical therapy to treat precancerous skin lesions in 1999, targets the heme pathway selectively in cancers. When provided with excess ALA, the fluorescent photosensitizer PpIX accumulates primarily in cancer tissue, and ALA PDD is used to identify bladder and brain cancers as a visual aid for surgical resection. ALA PDT has shown promising anecdotal clinical results in recurrent glioblastoma multiforme. ALA SDT represents a noninvasive way to activate ALA PDT and has the potential to achieve clinical success in the treatment of both intracranial and extracranial cancers...

Methylphenidate has an established role in the management of attention-deficit hyperactivity disorder and attentional deficit secondary to brain injury. Increasingly, methylphenidate is considered for the attentional deficit in paediatric brain tumour survivors. A small number of studies have explored the benefit of methylphenidate in this population; however, studies are of short duration and do not address the impact of medium to long-term use of methylphenidate on intellectual function. We identified six patients who are survivors of a paediatric brain tumour aged 12-18 years with greater than three years of use of methylphenidate for inclusion in a clinical case series...