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Multi-omic approach identifies hypoxic tumor-associated myeloid cells that drive immunobiology of high-risk pediatric ependymoma. (2023)
Journal Article
Griesinger, A. M., Riemondy, K., Eswaran, N., Donson, A. M., Willard, N., Prince, E. W., …Ritzmann, T. A. (2023). Multi-omic approach identifies hypoxic tumor-associated myeloid cells that drive immunobiology of high-risk pediatric ependymoma. iScience, 26(9), Article 107585. https://doi.org/10.1016/j.isci.2023.107585

Ependymoma (EPN) is a devastating childhood brain tumor. Single-cell analyses have illustrated the cellular heterogeneity of EPN tumors, identifying multiple neoplastic cell states including a mesenchymal-differentiated subpopulation which characteri... Read More about Multi-omic approach identifies hypoxic tumor-associated myeloid cells that drive immunobiology of high-risk pediatric ependymoma..

Pediatric-type high-grade neuroepithelial tumors with CIC gene fusion share a common DNA methylation signature (2023)
Journal Article
Sievers, P., Sill, M., Schrimpf, D., Abdullaev, Z., Donson, A. M., Lake, J. A., …Jones, D. T. W. (in press). Pediatric-type high-grade neuroepithelial tumors with CIC gene fusion share a common DNA methylation signature. npj Precision Oncology, 7, Article 30. https://doi.org/10.1038/s41698-023-00372-1

Pediatric neoplasms in the central nervous system (CNS) show extensive clinical and molecular heterogeneity and are fundamentally different from those occurring in adults. Molecular genetic testing contributes to accurate diagnosis and enables an opt... Read More about Pediatric-type high-grade neuroepithelial tumors with CIC gene fusion share a common DNA methylation signature.

Evaluating the efficacy and safety of single-agent etoposide intra-CSF chemotherapy in children and young people with relapsed/refractory central nervous system tumours (2023)
Journal Article
Butler, A., Meijer, L., Liu, J., Chohan, M., Jalloh, I., Macarthur, D., …Dandapani, M. (2023). Evaluating the efficacy and safety of single-agent etoposide intra-CSF chemotherapy in children and young people with relapsed/refractory central nervous system tumours. Child's Nervous System, 39, 1537-1544. https://doi.org/10.1007/s00381-023-05872-w

Purpose The aim of the project was to evaluate intra-CSF etoposide administration in a palliative setting for children and young people with relapsed/refractory central nervous system (CNS) tumours, with the primary endpoints being overall survival... Read More about Evaluating the efficacy and safety of single-agent etoposide intra-CSF chemotherapy in children and young people with relapsed/refractory central nervous system tumours.

Optimising biomarkers for accurate ependymoma diagnosis, prognostication and stratification within International Clinical Trials: A BIOMECA study (2023)
Journal Article
Chapman, R. J., Ghasemi, D. R., Andreiuolo, F., Zschernack, V., Tauziede Espariat, A., Buttarelli, F. R., …Biomarkers of Ependymoma in Childhood and Adolescence (BIOMECA) Consortium. (2023). Optimising biomarkers for accurate ependymoma diagnosis, prognostication and stratification within International Clinical Trials: A BIOMECA study. Neuro-Oncology, 25(10), 1871–1882. https://doi.org/10.1093/neuonc/noad055

Background Accurate identification of brain tumour molecular subgroups is increasingly important. We aimed to establish the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society... Read More about Optimising biomarkers for accurate ependymoma diagnosis, prognostication and stratification within International Clinical Trials: A BIOMECA study.

Spatial transcriptomic analysis delineates epithelial and mesenchymal subpopulations and transition stages in childhood ependymoma (2022)
Journal Article
Fu, R., Norris, G. A., Willard, N., Griesinger, A. M., Riemondy, K. A., Amani, V., …Donson, A. M. (2023). Spatial transcriptomic analysis delineates epithelial and mesenchymal subpopulations and transition stages in childhood ependymoma. Neuro-Oncology, 25(4), 786-798. https://doi.org/10.1093/neuonc/noac219

Background The diverse cellular constituents of childhood brain tumor ependymoma, recently revealed by single cell RNA-sequencing, may underly therapeutic resistance. Here we use spatial transcriptomics to further advance our understanding of the tum... Read More about Spatial transcriptomic analysis delineates epithelial and mesenchymal subpopulations and transition stages in childhood ependymoma.

Impact of Tumour Epstein–Barr Virus Status on Clinical Outcome in Patients with Classical Hodgkin Lymphoma (cHL): A Review of the Literature and Analysis of a Clinical Trial Cohort of Children with cHL (2022)
Journal Article
Nohtani, M., Vrzalikova, K., Ibrahim, M., Powell, J. E., Fennell, É., Morgan, S., …Murray, P. G. (2022). Impact of Tumour Epstein–Barr Virus Status on Clinical Outcome in Patients with Classical Hodgkin Lymphoma (cHL): A Review of the Literature and Analysis of a Clinical Trial Cohort of Children with cHL. Cancers, 14(17), Article 4297. https://doi.org/10.3390/cancers14174297

In this study, we have re-evaluated how EBV status influences clinical outcome. To accomplish this, we performed a literature review of all studies that have reported the effect of EBV status on patient outcome and also explored the effect of EBV pos... Read More about Impact of Tumour Epstein–Barr Virus Status on Clinical Outcome in Patients with Classical Hodgkin Lymphoma (cHL): A Review of the Literature and Analysis of a Clinical Trial Cohort of Children with cHL.

Lipoprotein Deprivation Reveals a Cholesterol-Dependent Therapeutic Vulnerability in Diffuse Glioma Metabolism (2022)
Journal Article
Wood, J., Abdelrazig, S., Evseev, S., Ortori, C., Castellanos-Uribe, M., May, S. T., …Rahman, R. (2022). Lipoprotein Deprivation Reveals a Cholesterol-Dependent Therapeutic Vulnerability in Diffuse Glioma Metabolism. Cancers, 14(16), Article 3873. https://doi.org/10.3390/cancers14163873

Poor outcomes associated with diffuse high-grade gliomas occur in both adults and children, despite substantial progress made in the molecular characterisation of the disease. Targeting the metabolic requirements of cancer cells represents an alterna... Read More about Lipoprotein Deprivation Reveals a Cholesterol-Dependent Therapeutic Vulnerability in Diffuse Glioma Metabolism.

Characterisation of Expression the Arginine Pathway Enzymes in Childhood Brain Tumours to Determine Susceptibility to Therapeutic Arginine Depletion (2022)
Journal Article
Bishop, E., Dimitrova, M., Froggatt, A., Estevez-Cebrero, M., Storer, L. C. D., Mussai, F., …Dandapani, M. (2022). Characterisation of Expression the Arginine Pathway Enzymes in Childhood Brain Tumours to Determine Susceptibility to Therapeutic Arginine Depletion. BioMed Research International, 2022, Article 9008685. https://doi.org/10.1155/2022/9008685

Despite significant improvements in treatment and survival in paediatric cancers, outcomes for children with brain tumours remain poor. Novel therapeutic approaches are needed to improve survival and quality of survival. Extracellular arginine depend... Read More about Characterisation of Expression the Arginine Pathway Enzymes in Childhood Brain Tumours to Determine Susceptibility to Therapeutic Arginine Depletion.

Toward Improved Diagnosis Accuracy and Treatment of Children, Adolescents, and Young Adults With Ependymoma: The International SIOP Ependymoma II Protocol (2022)
Journal Article
Leblond, P., Massimino, M., English, M., Ritzmann, T. A., Gandola, L., Calaminus, G., …Frappaz, D. (2022). Toward Improved Diagnosis Accuracy and Treatment of Children, Adolescents, and Young Adults With Ependymoma: The International SIOP Ependymoma II Protocol. Frontiers in Neurology, 13, Article 887544. https://doi.org/10.3389/fneur.2022.887544

Background: The clinical management of ependymoma in childhood and adolescence is complex and the clinicobiopathological correlates of outcome remain poorly understood. This international SIOP Ependymoma II (SIOP EPII) trial aims to improve the outco... Read More about Toward Improved Diagnosis Accuracy and Treatment of Children, Adolescents, and Young Adults With Ependymoma: The International SIOP Ependymoma II Protocol.

Phase II study of intravenous etoposide in patients with relapsed ependymoma (CNS 2001 04) (2022)
Journal Article
Apps, J. R., Maycock, S., Ellison, D. W., Jaspan, T., Ritzmann, T. A., Macarthur, D., …Picton, S. (2022). Phase II study of intravenous etoposide in patients with relapsed ependymoma (CNS 2001 04). Neuro-Oncology Advances, 4(1), Article vdac053. https://doi.org/10.1093/noajnl/vdac053

Background Relapsed ependymoma has a dismal prognosis, and the role of chemotherapy at relapse remains unclear. This study prospectively evaluated the efficacy of intensive intravenous (IV) etoposide in patients less than 21 years of age with relaps... Read More about Phase II study of intravenous etoposide in patients with relapsed ependymoma (CNS 2001 04).

Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: a multicenter study (2022)
Journal Article
Withey, S. B., MacPherson, L., Oates, A., Powell, S., Novak, J., Abernethy, L., …Peet, A. C. (2022). Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: a multicenter study. Pediatric Radiology, 52(6), 1134-1149. https://doi.org/10.1007/s00247-021-05266-7

Background Relative cerebral blood volume (rCBV) measured using dynamic susceptibility-contrast MRI can differentiate between low- and high-grade pediatric brain tumors. Multicenter studies are required for translation into clinical practice. Obj... Read More about Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: a multicenter study.

Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors (2022)
Journal Article
Branter, J., Estevez-Cebrero, M., Diksin, M., Griffin, M., Castellanos-Uribe, M., May, S., …Smith, S. (2022). Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors. International Journal of Molecular Sciences, 23(4), Article 1982. https://doi.org/10.3390/ijms23041982

The lack of treatment options for high-grade brain tumors has led to searches for alternative therapeutic modalities. Electrical field therapy is one such area. The Optune™ system is an FDA-approved novel device that delivers continuous alternating e... Read More about Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors.

SIOP Ependymoma I: Final results, long term follow-up and molecular analysis of the trial cohort: A BIOMECA Consortium Study (2022)
Journal Article
Ritzmann, T. A., Chapman, R. J., Kilday, J., Thorp, N., Modena, P., Dineen, R. A., …Grundy, R. G. (2022). SIOP Ependymoma I: Final results, long term follow-up and molecular analysis of the trial cohort: A BIOMECA Consortium Study. Neuro-Oncology, 24(6), 936–948. https://doi.org/10.1093/neuonc/noac012

Background SIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) of non-metastatic intracranial ependymoma in children aged 3 to 21 years treated with a staged management strategy. A further aim was to asses... Read More about SIOP Ependymoma I: Final results, long term follow-up and molecular analysis of the trial cohort: A BIOMECA Consortium Study.

Meta-Analysis of Apparent Diffusion Coefficient in Pediatric Medulloblastoma, Ependymoma, and Pilocytic Astrocytoma (2021)
Journal Article
Dury, R. J., Lourdusamy, A., Macarthur, D. C., Peet, A. C., Auer, D. P., Grundy, R. G., & Dineen, R. A. (2022). Meta-Analysis of Apparent Diffusion Coefficient in Pediatric Medulloblastoma, Ependymoma, and Pilocytic Astrocytoma. Journal of Magnetic Resonance Imaging, 56(1), 147-157. https://doi.org/10.1002/jmri.28007

Background: Medulloblastoma, ependymoma, and pilocytic astrocytoma are common pediatric posterior fossa tumors. These tumors show overlapping characteristics on conventional MRI scans, making diagnosis difficult. Purpose: To investigate whether appar... Read More about Meta-Analysis of Apparent Diffusion Coefficient in Pediatric Medulloblastoma, Ependymoma, and Pilocytic Astrocytoma.

Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism (2021)
Journal Article
Alfardus, H., de los Angeles Estevez Cebrero, M., Rowlinson, J., Lourdusamy, A., Abdelrazig, S., Ortori, C., …Smith, S. (2021). Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism. Scientific Reports, 11(1), Article 15908. https://doi.org/10.1038/s41598-021-95289-9

While specific microRNA (miRNA) signatures have been identified in glioblastoma (GBM), the intratumour heterogeneity in miRNA expression has not yet been characterised. In this study, we reveal significant alterations in miRNA expression across three... Read More about Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism.

EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY (2021)
Journal Article
Ritzmann, T. A., Chapman, R. J., Macarthur, D., Mallucci, C., Kilday, J., Thorp, N., …Grundy, R. G. (2021). EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY. Neuro-Oncology, 23(Supplement 1), i14. https://doi.org/10.1093/neuonc/noab090.054

Introduction Surgery and radiotherapy are established childhood ependymoma treatments. The efficacy of chemotherapy has been debated. We report final results of the SIOP Ependymoma I trial, with 12-year follow-up, in the context of a post-hoc analys... Read More about EPEN-04. SIOP EPENDYMOMA I: FINAL RESULTS, LONG TERM FOLLOW-UP AND MOLECULAR ANALYSIS OF THE TRIAL COHORT: A BIOMECA CONSORTIUM STUDY.

EPEN-08. THE TREM1 POSITIVE HYPOXIC MYELOID SUBPOPULATION IN POSTERIOR FOSSA EPENDYMOMA (2021)
Journal Article
Willard, N., Donson, A., Ritzmann, T., Grundy, R., Jackson, A., Hankinson, T., …Foreman, N. (2021). EPEN-08. THE TREM1 POSITIVE HYPOXIC MYELOID SUBPOPULATION IN POSTERIOR FOSSA EPENDYMOMA. Neuro-Oncology, 23(Supplement 1), i15. https://doi.org/10.1093/neuonc/noab090.058

We have previously shown the importance of immune factors in posterior fossa ependymoma (PF EPN). Recently, we found eight transcriptionally unique subpopulations of myeloid cells infiltrating PF EPN with one population particularly enriched in PFA1... Read More about EPEN-08. THE TREM1 POSITIVE HYPOXIC MYELOID SUBPOPULATION IN POSTERIOR FOSSA EPENDYMOMA.

EPEN-07. SINGLE-CELL RNA SEQUENCING IDENTIFIES A UNIQUE MYELOID SUBPOPULATION ASSOCIATED WITH MESENCHYMAL TUMOR SUBPOPULATION IN POOR OUTCOME PEDIATRIC EPENDYMOMA (2021)
Journal Article
Griesinger, A., Riemondy, K., Donson, A., Willard, N., Prince, E., Harris, F., …Ritzmann, T. (2021). EPEN-07. SINGLE-CELL RNA SEQUENCING IDENTIFIES A UNIQUE MYELOID SUBPOPULATION ASSOCIATED WITH MESENCHYMAL TUMOR SUBPOPULATION IN POOR OUTCOME PEDIATRIC EPENDYMOMA. Neuro-Oncology, 23(Supplement 1), i14-i15. https://doi.org/10.1093/neuonc/noab090.057

We have previously shown immune gene phenotype variations between posterior fossa ependymoma subgroups. PFA1 tumors chronically secrete IL-6, which induces secretion of myeloid cell IL-8 and pushes the infiltrating myeloid cells to an immune suppress... Read More about EPEN-07. SINGLE-CELL RNA SEQUENCING IDENTIFIES A UNIQUE MYELOID SUBPOPULATION ASSOCIATED WITH MESENCHYMAL TUMOR SUBPOPULATION IN POOR OUTCOME PEDIATRIC EPENDYMOMA.

EPEN-11. TUMOR DIFFERENTIATION IMPACTS THE BIOLOGY OF RECURRENCE IN CHILDHOOD POSTERIOR FOSSA EPENDYMOMA (2021)
Journal Article
Donson, A., Ritzmann, T., Willard, N., Griesinger, A., Amani, V., Harris, F., …Foreman, N. (2021). EPEN-11. TUMOR DIFFERENTIATION IMPACTS THE BIOLOGY OF RECURRENCE IN CHILDHOOD POSTERIOR FOSSA EPENDYMOMA. Neuro-Oncology, 23(Supplement 1), i15-i16. https://doi.org/10.1093/neuonc/noab090.061

Ependymoma (EPN) of childhood is curable in only 50% of cases, with recurrences in the remainder that are refractory to treatment. In recent years significant advances have been made in understanding the molecular and cellular biology of EPN. Recent... Read More about EPEN-11. TUMOR DIFFERENTIATION IMPACTS THE BIOLOGY OF RECURRENCE IN CHILDHOOD POSTERIOR FOSSA EPENDYMOMA.