PLAG1 fusions define a third subtype of CNS embryonal tumor with PLAG family gene alteration.

CNS embryonal tumors with PLAGL amplification (ET, PLAGL) are a recently described tumor type marked by amplification of one of the PLAG family genes, PLAGL1 or PLAGL2. Separately, a supratentorial, ependymoma-like CNS tumor type with PLAG family alteration, namely PLAGL1 fusion, was also reported (NET_PLAGL1). Here, we use DNA methylation profiling in combination with copy number, RNA-seq, and histological analysis to characterize and classify a novel group of CNS embryonal tumors harboring PLAG1 gene fusions (n=12).

Management of Paediatric Cancers Associated With Bloom Syndrome.

Bloom syndrome (BS) is a rare genetic disorder associated with an elevated risk of cancer. In a national multicentre study, nine paediatric patients with BS and cancer were analysed. Median age at cancer diagnosis was 12 years.

Feasibility and efficacy of MEMMAT-like regimen in heavily pretreated adult patients with recurrent malignant embryonal brain tumors: A series of 6 cases.

Background: The prognosis of adult patients with recurrent malignant embryonal brain tumors remains poor due to the lack of effective and validated treatment. A metronomic and antiangiogenic chemotherapy regimen called MEMMAT was developed in children, with promising results. Additional data on feasibility, tolerance, and efficacy in adults are necessary.

Pediatric Head and Neck Germ Cell Tumors: Current Management and Risk of Malignant Transformation.

Background And Aims: Head and neck germ cell tumors (HN-GCTs), excluding the central nervous system, are rare and frequently contain mature or immature teratoma (MIT) compounds. The aims of this study were to analyze the risk of malignant transformation after MIT HN-GCTs, to describe treatments and sequelae, and to propose recommendations for the follow up of these patients.

Methods: National multicentric retrospective study of all patients aged from birth to 17 years, treated in France between 2000 and 2021 for a HN-GCT of all histotypes.

Comparative Clinical and Imaging-Based Evaluation of Therapeutic Modalities in CNS Embryonal Tumours With PLAGL Amplification.

Aims: Embryonal tumours with PLAGL1 or PLAGL2 amplification (ET, PLAGL) show substantial heterogeneity regarding their clinical characteristics and have been treated inconsistently, resulting in diverse outcomes. In this study, we aimed to evaluate the clinical behaviour of ET, PLAGL and elucidate their response pattern across the different applied treatment regimens.

Methods: We conducted an in-depth retrospective analysis of clinical and serial imaging data of 18 patients with ET, PLAGL (nine each of PLAGL1 and PLAGL2 amplified).

Real-world pharmacokinetics of trametinib in pediatric low-grade glioma.

Purpose: Trametinib, a MEK1/2 inhibitor, has emerged as a promising treatment for pediatric patients with low-grade gliomas (LGG). However, trametinib exhibits significant inter-individual pharmacokinetic (PK) variability, and studies in adults demonstrated an exposure-efficacy relationship. This study aimed to evaluate the PK profile of trametinib in pediatric routine care and explore potential exposure-outcome relationships.

Cervical Lymph Node Invasion in Pediatric Salivary Gland Malignancies: Clinical Overview and Therapeutic Implications.

Background And Aims: Pediatric salivary gland malignancies (SGM) present challenges in managing cervical nodes. We aimed to characterize lymph node invasion to inform decisions regarding the need of systematic wide lymph node dissection (WLND).

Methods: International retrospective study, conducted across seven large French and American pediatric centers, including pediatric patients (0-18 years) diagnosed with SGM from 2000 to 2020.

Causally Mapping the Cerebellum in Children and Young Adults: from Motor to Cognition.

While the cerebellum's role in orchestrating motor execution and routines is well established, its functional role in supporting cognition is less clear. Previous studies claim that motricity and cognition are mapped in different areas of the cerebellar cortex, with an anterior/posterior dichotomy. However, most of the studies supporting this claim either use correlational methods (neuroimaging) or are lesion studies that did not consider central covariates (such as age, gender, treatment presence, and deep nuclei impairment) known to influence motor and cognitive recoveries in patients.

Nanopore sequencing as a cutting-edge technology for medulloblastoma classification.

Background: Medulloblastoma (MB) is one of the most prevalent embryonal malignant brain tumors. Current classification organizes these tumors into 4 molecular subgroups (WNT, SHH, Group 3, and Group 4 MB). Recently, a comprehensive classification has been established, identifying numerous subtypes, some of which exhibit a poor prognosis.

Intensive pediatric chemotherapy regimen (PNET HR+5) in adult high-risk medulloblastoma and pineoblastoma patients.

Background: High-risk medulloblastoma (HRMB) is rare in adults. The 5-year overall survival rate is less than 60%. We present here a retrospective analysis of adults treated with an intensive pediatric chemo-radiotherapy regimen PNET HR + 5: NCT00936156.

Postzygotic mosaicism of SMARCB1 variants in patients with rhabdoid tumors: A not-so-rare condition exposing to successive tumors.

Background: Rhabdoid tumors (RT) are aggressive, rare tumors predominantly affecting young children, characterized by biallelic SMARCB1 gene inactivation. While most SMARCB1 alterations are acquired de novo, a third of cases exhibit germline alterations, defining Rhabdoid Tumors Predisposition Syndrome. With the increased sensitivity of next-generation sequencing (NGS), mosaicisms in genes linked to genetic diseases are more detectable.

Medulloblastomas with pathogenic variants: A weakly penetrant syndrome with a restricted spectrum in a limited age window.

Background: pathogenic variants (PV) have been recently identified as the most frequent variants predisposing to Sonic Hedgehog (SHH) medulloblastomas (MB); however, guidelines are still lacking for genetic counseling in this new syndrome.

Methods: We retrospectively reviewed clinical and genetic data of a French series of 29 -mutated MB.

Results: All patients developed SHH-MB, with a biallelic inactivation of found in 24 tumors.

Renal toxicity of ifosfamide in children with cancer: an exploratory study integrating aldehyde dehydrogenase enzymatic activity data and a wide-array urinary metabolomics approach.

Background: Ifosfamide is a major anti-cancer drug in children with well-known renal toxicity. Understanding the mechanisms underlying this toxicity could help identify children at increased risk of toxicity.

Methods: The IFOS01 study included children undergoing ifosfamide-based chemotherapy for Ewing sarcoma or rhabdomyosarcoma.

Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.

Purpose: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization.

Mutational signature, cancer driver genes mutations and transcriptomic subgroups predict hepatoblastoma survival.

Background: Hepatoblastoma is the most frequent pediatric liver cancer. The current treatments lead to 80% of survival rate at 5 years. In this study, we evaluated the clinical relevance of molecular features to identify patients at risk of chemoresistance, relapse and death of disease.

Oncological and endocrinological outcomes for children and adolescents with testicular and ovarian sex cord-stromal tumors. Results of the TGM13 National Registry.

Rationale: Sex cord-stromal tumors (SCST) are hormonally active and rare. The aim was to describe their endocrinological presentation and outcomes.

Method: Patients (< 19 years) registered in the TGM13 registry between 2014 and 2021 for SCST were selected.

METRO-PD1: Phase 1 study of nivolumab in combination with metronomic chemotherapy in children and adolescents with relapsing/refractory solid tumors.

Background: This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors.

Objectives: To evaluate the feasibility and safety of the three regimens METHODS: Patients aged < 18 years were enrolled. Nivolumab was combined with cyclophosphamide and vinblastine (arm A), capecitabine (arm B), or cyclophosphamide, vinblastine and capecitabine (arm C).

Antiseizure effect of MEK inhibitor in a child with neurofibromatosis type 1-Developmental and epileptic encephalopathy and optic pathway glioma.

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder due to a mutation in NF1 gene, resulting in phenotypically heterogeneous systemic manifestations. Patients with NF1 are prone to develop neoplasms of the central nervous system (CNS) and are particularly at risk for optic pathway gliomas (OPG). Epilepsy is another recognized neurologic complication in patients with NF1, with a prevalence estimated between 4% and 14%.

Outcome and late effects of patients treated for childhood vaginal malignant germ cell tumors.

Purpose: Vaginal malignant germ cell tumors (MGCT) are rare, occurring in children less than 2 years old and raise the question of the optimal local treatment.

Methods: We included children treated for vaginal MGCT according to the French TGM-95/2013 regimen. Patients were classified as standard risk (SR: localized disease and alpha-fetoprotein (AFP) < 10,000 ng/mL) or high risk (HiR: metastatic and/or AFP > 10,000 ng/mL) and were treated, respectively, with three to five VBP (vinblastine-bleomycin-cisplatin) or four to six VIP (etoposide-ifosfamide-cisplatin), followed by conservative surgery and/or brachytherapy in case of post-chemotherapy residuum.

Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol.

Background: The HIT-SKK protocol is used for low/standard-risk medulloblastomas in young children with the aim to eliminate cranial irradiation and its neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders. This study describes the risk factors and course of LE, and investigates its correlation with neurocognitive impact.