Ependymoma

P2, N=5, Active, not recruiting, National Cancer Institute (NCI) | N=49 --> 5 | Trial completion date: Sep 2027 --> Apr 2025 | Trial primary completion date: Sep 2027 --> Mar 2024

P2, N=53, Completed, Celgene | Trial primary completion date: Nov 2018 --> Sep 2023

The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.

P1, N=8, Completed, Istari Oncology, Inc. | Active, not recruiting --> Completed | Phase classification: P1b --> P1 | N=12 --> 8

P=N/A, N=186, Completed, Giselle Sholler | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Jan 2024 | Trial primary completion date: Jun 2025 --> Jan 2024

P1, N=32, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial completion date: Mar 2024 --> Sep 2024

P1, N=31, Completed, The Hospital for Sick Children | Active, not recruiting --> Completed | Trial completion date: Jul 2022 --> Mar 2024

P1/2, N=17, Terminated, SK Life Science, Inc. | N=96 --> 17 | Trial completion date: Sep 2024 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2024 --> Mar 2024; The study has been terminated based on portfolio prioritization. No safety trends or issues were identified at any dose level.

Methylation analysis in neurooncology is essential for unclear tumor morphology or divergence between histological and clinical data. In our case, this technique confirmed benign nature of tumor, and we preferred follow-up without unnecessary adjuvant treatment.

Our results underscore the multifactorial nature of tumor aggressiveness in EPNs of the spinal region. This study enhances our knowledge of the clinical and pathological features of Sp-EPNs and MPEs and highlights the need for better diagnostic and prognostic markers in these rare tumors.

Our results unveiled the distinct TME across brain tumor types and provided a transcriptomic landscape. Our findings may contribute to realizing future precision medicine, providing a basic rationale for the therapeutics of brain tumors.

P1, N=50, Recruiting, Pediatric Brain Tumor Consortium | Active, not recruiting --> Recruiting

P=N/A, N=72, Not yet recruiting, University Hospital Regensburg

P1, N=68, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Mar 2025 --> May 2024

Patients with lower expression of TOP2A, CDK1, PCNA, and ACTA2 had a longer OS and PFS. The differential expressed genes identified and the key pathways selected in this research provided unprecedented and promising targets for diagnosis and treatment of EPN patients.

P1, N=25, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

The pathology confirmed a diagnosis of World Health Organization grade II ependymoma. The management of ependymomas in adults often starts with surgical resection for cytoreduction followed by postoperative radiotherapy for World Health Organization grade II and grade III at least.1-4 Spinal cord ependymomas tend to have favorable prognosis, except when carrying an MYCN gene amplification.5,6.

P1, N=24, Active, not recruiting, Gregory K. Friedman, MD | Recruiting --> Active, not recruiting | N=15 --> 24

P1, N=6, Completed, University of Colorado, Denver | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Jul 2023

CSF liquid biopsy has potential as a minimally invasive method of disease detection for measuring treatment response and longitudinal disease surveillance. lpWGS on CSF-derived cfDNA can identify tumor-derived sCNVs even when CSF cytology is negative for malignant cells. lpWGS can reveal sCNVs that are clinically actionable without need for a tissue biopsy.

Due to the scarcity of patient samples, the development of preclinical in vitro and in vivo models that recapitulate patient tumors is imperative when testing therapeutic approaches for this rare cancer. In this review, we will survey ST-EPN modeling systems, addressing the strengths and limitations, application for therapeutic targeting, and current literature findings.

P2, N=15, Completed, Monica Thakar | Active, not recruiting --> Completed

P1/2, N=102, Suspended, Centre Oscar Lambret | Recruiting --> Suspended

To conclude, MYCN-amplified spinal ependymomas are rare tumors, accounting for ~ 4% of spinal cord ependymomas. Within the limitation of small sample size, MYCN IHC showed excellent concordance with MYCN gene amplification.

There was intratumor heterogeneity in anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and that the subtype differences may be due to differences in the origin of the cells.

In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered.

P1, N=24, Suspended, University of California, San Francisco | Recruiting --> Suspended

However, after 10 years, a recurrence was detected through magnetic resonance imaging (MRI) and the tumor was reclassified as AT/RT. We discuss the significance of SMARCB1 gene mutations in diagnosing AT/RT and describe our unique treatment approach involving surgery, radiation and anti-PD1 therapy in this patient.

This case adds to the existing literature of pediatric patients with spinal ependymomas and expands the cytogenetic findings that may be seen in patients with this tumor type. This case also highlights the value of cytogenetics and microarray analysis in solid tumors to provide a more accurate molecular diagnosis.

P1/2, N=91, Recruiting, University Hospital Heidelberg | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Jun 2024 --> Jun 2026

P1, N=6, Active, not recruiting, Hackensack Meridian Health | Trial completion date: Jan 2024 --> Apr 2024 | Trial primary completion date: Jan 2024 --> Apr 2024

Response Evaluation in Neurofibromatosis and Schwannomatosis currently recommends the Tinnitus Functional Index for the assessment of tinnitus in neurofibromatosis type 2 clinical trials.

P1/2, N=96, Active, not recruiting, SK Life Science, Inc. | Recruiting --> Active, not recruiting

P1, N=14, Completed, Washington University School of Medicine | Active, not recruiting --> Completed

Notably, genes downregulated at P14, such as Kif11 and HMGB2, exhibited significant enrichment across all pediatric brain tumor groups, suggesting the importance of astrocytic gene repression during cerebellar development to these tumor subtypes. Collectively, our studies describe gene expression patterns during cerebellar astrocyte development, with potential implications for pediatric tumors originating in the cerebellum.

P=N/A, N=80, Recruiting, Pediatric Brain Tumor Consortium | Active, not recruiting --> Recruiting

Relapsing tumors displayed a higher proportion of cell-dense areas (p = 0.036), a change in PF-EPN-A methylation subtypes (13/32 patients), and novel chromosome 1q gains and 6q losses (12/32 cases) compared to corresponding primary tumors. Our data suggest that PF-EPN-A ependymomas habor a previously unrecognized intratumoral heterogeneity with clinical implications, which has to be accounted for when selecting diagnostic material, inter alia, by histological evaluation of the proportion of cell-dense areas.

In sum, our large-scale analysis of ependymomas provides robust information about molecular features and their clinical meaning. Our data are particularly relevant for rare and hardly explored tumor subtypes and seemingly benign variants that display higher recurrence rates than previously believed.

These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.

P1, N=50, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial completion date: Feb 2043 --> Jul 2043 | Trial primary completion date: Feb 2028 --> Jul 2028

To conclude, SOX10 can be incorporated into the IHC panel routinely used by neuropathologists in the diagnostic algorithm of embryonal tumours and for the subtyping of paediatric and adult-type HGG.

P2, N=62, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial completion date: Oct 2029 --> Oct 2030 | Trial primary completion date: Oct 2028 --> Oct 2029