Ependymoma

The neoplastic cells were immunoreactive for glial fibrillary acidic protein and negative for pancytokeratin. Considering the anatomopathological and immunohistochemical findings, the diagnosis was ependymoma grade II with melanocytic features, which is the first report of this neoplasm in any member of the genus Sapajus.

P2, N=100, Active, not recruiting, Scott R. Plotkin, MD, PhD | Recruiting --> Active, not recruiting

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

In cell-based studies, ALK2 inhibitors effectively attenuated activin A and BMP-induced Phosphorylated SMAD1/5 activation in fibroblasts from individuals with FOP in a dose-dependent manner. Thus, CDD-2789 is a valuable tool compound for further investigation of the biological functions of ALK2 and ALK1 and the therapeutic potential of specific inhibition of ALK2.

Targeted next-generation sequencing identified a TCF3::BEND2 fusion, validated by reverse transcription polymerase chain reaction and Sanger sequencing. This case broadens the genetic spectrum of high-grade neuroepithelial tumor and suggests that BEND2 alterations may serve as critical determinants for this EWSR1::BEND2 glioma subgroup within the methylation classifier.

P1/2, N=65, Recruiting, Nationwide Children's Hospital | Trial primary completion date: Nov 2025 --> Nov 2027

Molecular diagnostics through CGP testing served as an aid in diagnosis according to WHO2021. Cases where drug suggestions were feasible underwent treatment with targeted molecular therapies and checkpoint inhibitor. We experienced cases where hereditary cancer syndromes such as Lynch syndrome were diagnosed through the detection of germline pathogenic variants.

P1, N=29, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Oct 2024

P1, N=29, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

P2, N=23, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

P3, N=479, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Dec 2025

Comprehending the role of H3K27me3 in CNS tumors is vital for advancing diagnostic tools and therapeutic interventions, with the goal of enhancing patient outcomes and quality of life. This review underscores the importance of ongoing investigations into H3K27me to refine and optimize management strategies for CNS tumors, paving the way for improved personalized medicine practices in oncology.

The review encompasses various CNS tumor types, including subependymal giant cell astrocytoma, chordoid glioma, pituicytoma, ependymomas, astrocytomas, glioblastomas, medulloblastomas, and choroid plexus tumors, highlighting the potential role of TTF-1 in differentiating these neoplasms from other CNS and metastatic tumors. By synthesizing findings from multiple studies, this review underscores the diagnostic value of TTF-1 in the neuropathological evaluation of CNS tumors and suggests directions for future research to refine its clinical application.

P2, N=4, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

Spinal astroblastoma is a rare and highly aggressive tumor affecting children and young adults with a high recurrence rate and thus far not well-defined prognosis. The molecular signature of astroblastoma needs to be further characterized to establish a treatment-relevant classification and to allow a better prognostication. Currently, gross total resection combined with radiotherapy remains the mainstay of treatment for spinal astroblastoma.

P2, N=100, Recruiting, Medical University of Vienna | Trial completion date: Apr 2026 --> Apr 2030 | Trial primary completion date: Apr 2026 --> Apr 2030

P=N/A, N=500, Not yet recruiting, The Walter and Eliza Hall Institute of Medical Research (WEHI)

P1/2, N=68, Not yet recruiting, Washington University School of Medicine

P1, N=13, Completed, University of California, San Francisco | Suspended --> Completed | N=24 --> 13 | Trial completion date: Feb 2025 --> Sep 2024 | Trial primary completion date: Feb 2025 --> Sep 2024

No abstract available

P2, N=9, Active, not recruiting, National Cancer Institute (NCI) | N=49 --> 9 | Trial completion date: Sep 2024 --> Oct 2025

No abstract available

P2, N=10, Completed, Children's Hospital Medical Center, Cincinnati | Suspended --> Completed | Trial completion date: Jun 2025 --> May 2024 | Trial primary completion date: Dec 2024 --> May 2024

Overall, our results suggest that the all-in-one bimodal DNA/RNA panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification. The integrative pathological and molecular strategy could be valuable in confirmation of diagnosis and selection of treatment options for brain tumors.

Previous studies have demonstrated that CELF4 may play a pivotal role in the pathogenesis of SP-EP. Furthermore, this study developed and validated a prognostic prediction model in the form of a nomogram utilizing the SEER database, enabling clinicians to accurately assess treatment risks and benefits, thereby enhancing personalized therapeutic strategies and prognosis predictions.

The prognostic ability of procalcitonin and presepsin for detecting sepsis was high: AUROC = 0.875, cut-off value (Youden index) = 0.913 ng/mL, and AUROC = 0.774, with cut-off value (Youden index) of 526 pg/mL, respectively. A significant increase in aromatic microbial metabolites and biomarkers in non-survivor patients that is registered already in the first days of the development of complications indicates the appropriateness of assessing metabolic dysfunction for its timely targeted correction.

P2, N=650, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting

On the contrary, older children with supratentorial YAP1 fusion-positive ependymomas and type B posterior fossa tumors may survive with surgery alone. The paradigm shift regarding the behavior of the various childhood ependymoma subtypes will hopefully lead to targeted, individualized therapies and improved outcomes.

cBioPortal, CanSAR Black, and existing literature affirmed the association of these destabilizing mutations with posterior fossa ependymoma, uterine corpus carcinoma, and pediatric brain cancer. The current findings suggest these deleterious nonsynonymous single nucleotide polymorphisms as potential candidates for future functional annotations and validations associated with rare conditions, further aiding the development of precision medicine in rare diseases.

Taken together, we concluded that this tumor should be considered under the entity of ELTMD. This represents the first description of an adult patient with ELTMD harboring ZFTA::RELA fusion analyzed by DNA methylation profiling, supporting the establishment of ELTMD as a possible new tumor type.

In contrast, the PLAGL2 and PLAGL1 amplified cases showed either embryonal histology or contained an embryonal component with a significant degree of desmin staining, which could also serve to raise consideration for a PLAG entity when present. Continued compilation of associated clinical data and histopathologic findings will be critical for understanding emerging entities with PLAG-family genetic alterations.

We have previously identified that BET inhibition can selectively reduce growth of the NF2-null schwannoma and Schwann cells in vitro and tumorigenesis in vivo and, separately, reported that inhibition of Focal Adhesion Kinase 1 (FAK1) via crizotinib has antiproliferative effects in NF2-null Schwann cells...Further, we identify the mechanism of action through the downregulation of FAK1 transcription by BET inhibition, which potentiates inhibition of FAK by 100-fold. Our findings suggest that combined targeting of BET and FAK1 may offer a potential therapeutic option for the treatment of NF2-related schwannomas.

1. Specific chromatin modules accessible during brain development render distinct cell lineage programs at risk of transformation by pediatric fusion oncoproteins.2. Cross-species single cell ATAC and RNA (scMultiome) of mouse and human ependymoma (EPN) reveals diverse patterns of lineage differentiation programs that restrain oncogenic transformation.3. Early intermediate progenitor-like EPN cells establish a tumor cell hierarchy that mirrors neural differentiation programs.4. ZFTA-RELA transformation is compatible with distinct developmental epigenetic states requiring precise 'goldilocks' levels of fusion oncoprotein expression.5. Dominant tumor clones establish the entire EPN cellular hierarchy that reflects normal gliogenic and neurogenic differentiation programs.

P1, N=62, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Jun 2025

Cortically-based brain tumors in children constitute a unique set of tumors with variably aggressive biological behavior. As radiologists play an integral role on the multidisciplinary medical team, a clinically useful and easy-to-follow flowchart for the differential diagnoses of these complex brain tumors is essential.This proposed algorithm tree provides the latest insights into the typical imaging characteristics and epidemiologic data that differentiate the tumor entities, taking into perspective the 2021 World Health Organization's classification and highlighting classic as well as newly identified pathologic subtypes using current molecular understanding.ABBREVIATIONS: Astroblastoma=AB) Angiocentric glioma (AG) Atypical teratoid rhabdoid tumor (ATRT) Central Nervous System tumor (CNS) CNS neuroblastoma FOXR2-activated (NB-FOXR2) Desmoplastic infantile glioma/astrocytoma (DIG/DIA) Diffuse hemispheric glioma, H3 G34-mutant (DHG) Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) Dysembryoplastic neuroepithelial tumor (DNET) Embryonal Tumors with Multilayered Rosettes (ETMR) Ependymoma (EP) Focal cortical dysplasia (FCD) Ganglioglioma/gangliocytoma (GG) Infant-type hemispheric glioma (IHG) Intracranial pressure (ICP) Long-term epilepsy-associated tumors (LEATs) Pediatric diffuse low-grade gliomas (pLGG) MR spectroscopy (MRS) Multinodular and vacuolating neuronal tumor (MVNT) Overall survival (OS) Pediatric diffuse high-grade gliomas (pHGG).

Relapse patterns of specific EPN types are different. Future clinical trials, treatment adaptions, duration of surveillance and diagnostics should be planned incorporating entity-specific relapse information.

The final diagnosis of gliomas relies on a comprehensive combination of clinical evaluation, neuroimaging, pathological examination, and molecular analysis. Nonetheless, histopathological examination, along with IHC, remains the cornerstone of diagnosis.

P1, N=15, Terminated, Wake Forest University Health Sciences | Recruiting --> Terminated; Low accruals

Eight of 10 patients experienced recurrence, underscoring the aggressive nature of this disease. We suggest recognizing a new molecular subgroup of spinal astroblastoma and recommend testing newly diagnosed infratentorial astroblastomas for Ewing sarcoma RNA-binding protein 1-BEND2 fusion.

The obtained results indicate a correlation between gene expression and the WHO grade and subtype. Furthermore, our analysis showed that the integration between genomic and epigenetic pathways should now point the way to further molecular research.

The distinction between ST ependymoma subtypes and astroblastomas can be guided by several imaging features. These tumors share common imaging features that may help to differentiate ST ependymomas and astroblastomas from other pediatric ST tumors.

P1, N=19, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: Jul 2024 --> Oct 2024