RARE DISEASE
Central nervous system embryonal tumor
Central nervous system embryonal tumor
Central nervous system embryonal tumor
Synonyms: CNS PNET, Central nervous system primitive neuroectodermal tumor
Synonyms: CNS PNET, Central nervous system primitive neuroectodermal tumor
Synonyms: CNS PNET, Central nervous system primitive neuroectodermal tumor
Drug discovery
1
drug
With orphan designation
Overview
Central nervous system (CNS) embryonal tumors are aggressive pediatric malignancies originating from neuroectodermal cells, classified by molecular profiles per WHO guidelines [1][6][13]. Key entities include medulloblastoma, atypical teratoid/rhabdoid tumor (ATRT), and embryonal tumor with multilayered rosettes (ETMR). Tumors without definitive molecular signatures are designated NOS/NEC [1][16]. Prognosis varies by molecular subtype, with 5-year survival ranging from 10%-47% for advanced cases [3][13][17]. Multimodal treatment is standard, but molecular heterogeneity complicates therapeutic precision [8][13].
Therapies
Maximal safe resection + craniospinal radiation (age-dependent) + platinum-based chemotherapy [8][17][20]
Molecularly guided therapies (e.g., TOP1 inhibitors for ETMR, targeted agents for NEC tumors with actionable mutations) [3][8][13]
Ongoing trials explore epigenetic modulators and differentiation therapies [3][8][13]
Categories: rare neoplastic diseases, rare neurological diseases
Research Papers
223 drug discovery papers about Central nervous system embryonal tumor, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
223 drug discovery papers about Central nervous system embryonal tumor, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-29 | Primary Intraspinal Extradural Tumor Previously Classified as Primitive Neuroectodermal Tumor: Clinical and Imaging Findings: A Case Report
Primitive neuroectodermal tumors are aggressive childhood neoplasms that primarily arise in the Central Nervous System and rarely occur in the spine, and are currently reclassified within embryonal tumor groups. We present a case of a 15-year-old male with lower extremity weakness and sphincter dysfunction. Spinal magnetic resonance imaging revealed a well-defined extradural mass at thoracic (Th) 11–L1 with extraspinal extension and spinal cord compression. The tumor was completely resected, and histopathology was consistent with Primitive Neuroectodermal Tumor (former classification) although additional markers were inconclusive due to technical limitations. Neurological recovery was favorable. Sphincter dysfunction resolved by the time of hospital discharge, and lower extremity weaknes progressively improved, with near complete recovery at 3-month follow-up. However, seven years later, the tumor recurred and required repeat surgical treatment. This case highlights the importance of magnetic resonance imaging in the diagnosis, assessment of disease extent, and long-term follow-up of rare spinal embryonal tumors.
2026-07-25 | Intracerebroventricular B7-H3-targeting CAR T cells for non-pontine DMG and recurrent/refractory pediatric CNS tumors: a phase 1 trial
BACKGROUND: High-grade central nervous system (CNS) tumors carry a poor prognosis with limited curative options if first-line therapy fails. B7-H3 is expressed in many of these tumors, and chimeric antigen receptor (CAR) T cell therapy is an emerging immunotherapeutic strategy. METHODS: BrainChild-03 (NCT04185038) is a single-center, dose-escalation phase 1 study of repeated intracerebroventricular (ICV) B7-H3 CAR T cells in children and young adults with recurrent/refractory CNS tumors (Arms A, B) and diffuse intrinsic pontine glioma (DIPG, Arm C). Here, we report results from Arm B, in which patients with refractory/relapsed CNS tumors or pre- or post-progression non-pontine diffuse midline glioma (DMG) received repeated ICV infusions. Primary objectives were feasibility and safety/tolerability; secondary objectives included CAR T cell detection, disease response, and survival. RESULTS: Of 36 enrolled patients (atypical teratoid rhabdoid tumor n = 5, DMG n = 8, embryonal tumor with multilayer rosettes n = 2, ependymoma n = 4, high-grade glioma n = 6, medulloblastoma n = 8, pineoblastoma n = 3), manufacturing was successful for 35 patients, 26 of whom received therapy. Median age was 10 years (range 1-26). Dose escalation from 1 × 107 to 10 × 107 CAR T cells/dose identified this dose as the maximally tolerated dose regimen, with no dose-limiting toxicities observed. Across 181 total doses (median 7/patient), common adverse events included headache (n = 26), fever (n = 15), and nausea (n = 14). Median survival from first infusion was 11.5 months, ranging from 3.2 months (pineoblastoma, HGG) to 21.4 months (ependymoma); two patients achieved a partial response. CONCLUSIONS: Repeated ICV B7-H3 CAR T cell dosing is feasible and tolerable across a spectrum of pediatric CNS tumors, supporting continued investigation in future trials.
2026-06-30 | High-dose chemotherapy with autologous stem cell rescue in children under 5 years of age with central nervous system embryonal tumors: results from a prospective cohort in an upper-middle-income country
PURPOSE: High-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) has been employed to mitigate the long-term side effects of radiotherapy and improve survival outcomes in infants with embryonal central nervous system (CNS) tumors. METHODS: This prospective study, supported by federal funding from the National Oncological Care Support Program, included children younger than 5 years of age with newly diagnosed CNS embryonal tumors treated with surgery and HDCT/ASCR. RESULTS: Between 2016 and 2019, 36 patients were included: 22 with medulloblastoma (MB) and 14 with other CNS embryonal tumors. In the MB cohort, the mean age was 2.5 years, 13 were male. Gross total resection (GTR) was achieved in 18 patients; 15 had non-metastatic disease (M0). Among non-MB patients, the mean age was 2.7 years, 11 were female. Nine patients had GTR; 12 had M0. According to the MB molecular subgroup, the 2- and 5-year event-free survival (EFS) rates for the SHH subgroup were 76.9%, and overall survival (OS) was 92.3%. For the non-WNT/non-SHH subgroup, the 2- and 5-year EFS rates were 33.3% and 22.2%, and OS, 66.7% and 55.6%, respectively. Two SHH and five non-WNT/non-SHH patients were successfully salvaged with craniospinal irradiation after a mean of 12 months (range, 7-36 months). Among non-MB patients, the 2- and 5-year EFS and OS were 28.6/19.0% and 42.9/32.1%, respectively. All patients developed grade 3-4 mucositis/typhlitis and febrile neutropenia and 13.9% invasive fungal infections during HDCT. CONCLUSION: HDCT/ASCR is feasible in a middle-income country setting and provides favorable outcomes in SHH medulloblastoma. However, prognosis remains poor for non-SHH MB and other embryonal tumors, highlighting the need for novel molecularly guided therapies.
2026-06-24 | Guidance for the Diagnosis and Treatment of Rare Embryonal and Sarcomatous Brain Tumors—a Report from the Central Nervous System-International Registry for Rare Embryonal and Sarcomatous Tumors German Society of Pediatric Oncology and Hematology Study Group
Abstract: With the advent of multi-omic molecular profiling techniques, central nervous system tumor types previously not recognized by conventional neuropathological assessment have emerged, particularly among tumors formerly termed as "CNS- primitive neuroectodermal tumors." Given the diverse histopathological, molecular, radiological, and clinical characteristics of these tumors, diagnostic approaches and treatment strategies need to be adapted to our increasing knowledge. The small number of patients per year for individual tumor types precludes large cohort studies and mandates international cooperation and harmonization. To this end, the SIOPE Brain Tumor Group together with the European Reference Network for Pediatric Cancers has published the European Standards of Clinical Practice guidelines for rare embryonal and sarcomatous tumors.
2026-06-23 | ID #744 Epidemiological profile of central nervous system tumors in patients followed at the neuro-oncology outpatient clinic of ITACI (1994-2025)
Abstract Introduction Central nervous system (CNS) tumors are a major cause of morbidity and mortality in children and adolescents, often leading to neurological sequelae and reduced quality of life. In Brazil, epidemiological data from specialized centers remain scarce, limiting public health planning. The Instituto de Tratamento do Câncer Infantil (ITACI) is a national reference center in pediatric oncology. This study aimed to describe the epidemiological profile of CNS tumors treated at ITACI. Methods This retrospective, descriptive study analyzed the institutional database of the ITACI neuro-oncology outpatient clinic. All patients with confirmed CNS tumors followed between 1994 and 2025 were included. Variables analyzed were histological diagnosis and diagnostic frequency. Data were evaluated using descriptive statistics and expressed as absolute and relative frequencies. Results A total of 468 patients were analyzed, with slight male predominance (52.78%; n = 247). There was a progressive increase in diagnoses over time, with higher frequencies in recent years, especially 2025 (13.68%) and 2023 (12.61%). The category “Others”, grouping rare tumors, represented the most frequent diagnosis (18.80%; n = 88), reflecting the heterogeneity of CNS neoplasms. Among specific tumors, medulloblastoma was most prevalent (17.52%; n = 82), followed by pilocytic astrocytoma (11.54%; n = 54), low-grade gliomas (7.69%; n = 36), ependymomas (6.62%; n = 31), and germ cell tumors (5.77%; n = 27). Other relevant diagnoses included optic pathway gliomas, craniopharyngiomas, diffuse brainstem gliomas, and high-grade gliomas. Conclusion The study demonstrated an epidemiological pattern consistent with the literature, with predominance of embryonal and glial tumors and slight male predominance. The high frequency of rare tumors highlights the importance of specialized centers for accurate diagnosis and management. These findings reinforce ITACI’s role as a national reference center and contribute to Brazilian epidemiological data, supporting healthcare planning and public policy development in pediatric neuro-oncology.
2026-07-29 | Primary Intraspinal Extradural Tumor Previously Classified as Primitive Neuroectodermal Tumor: Clinical and Imaging Findings: A Case Report
Primitive neuroectodermal tumors are aggressive childhood neoplasms that primarily arise in the Central Nervous System and rarely occur in the spine, and are currently reclassified within embryonal tumor groups. We present a case of a 15-year-old male with lower extremity weakness and sphincter dysfunction. Spinal magnetic resonance imaging revealed a well-defined extradural mass at thoracic (Th) 11–L1 with extraspinal extension and spinal cord compression. The tumor was completely resected, and histopathology was consistent with Primitive Neuroectodermal Tumor (former classification) although additional markers were inconclusive due to technical limitations. Neurological recovery was favorable. Sphincter dysfunction resolved by the time of hospital discharge, and lower extremity weaknes progressively improved, with near complete recovery at 3-month follow-up. However, seven years later, the tumor recurred and required repeat surgical treatment. This case highlights the importance of magnetic resonance imaging in the diagnosis, assessment of disease extent, and long-term follow-up of rare spinal embryonal tumors.
2026-07-25 | Intracerebroventricular B7-H3-targeting CAR T cells for non-pontine DMG and recurrent/refractory pediatric CNS tumors: a phase 1 trial
BACKGROUND: High-grade central nervous system (CNS) tumors carry a poor prognosis with limited curative options if first-line therapy fails. B7-H3 is expressed in many of these tumors, and chimeric antigen receptor (CAR) T cell therapy is an emerging immunotherapeutic strategy. METHODS: BrainChild-03 (NCT04185038) is a single-center, dose-escalation phase 1 study of repeated intracerebroventricular (ICV) B7-H3 CAR T cells in children and young adults with recurrent/refractory CNS tumors (Arms A, B) and diffuse intrinsic pontine glioma (DIPG, Arm C). Here, we report results from Arm B, in which patients with refractory/relapsed CNS tumors or pre- or post-progression non-pontine diffuse midline glioma (DMG) received repeated ICV infusions. Primary objectives were feasibility and safety/tolerability; secondary objectives included CAR T cell detection, disease response, and survival. RESULTS: Of 36 enrolled patients (atypical teratoid rhabdoid tumor n = 5, DMG n = 8, embryonal tumor with multilayer rosettes n = 2, ependymoma n = 4, high-grade glioma n = 6, medulloblastoma n = 8, pineoblastoma n = 3), manufacturing was successful for 35 patients, 26 of whom received therapy. Median age was 10 years (range 1-26). Dose escalation from 1 × 107 to 10 × 107 CAR T cells/dose identified this dose as the maximally tolerated dose regimen, with no dose-limiting toxicities observed. Across 181 total doses (median 7/patient), common adverse events included headache (n = 26), fever (n = 15), and nausea (n = 14). Median survival from first infusion was 11.5 months, ranging from 3.2 months (pineoblastoma, HGG) to 21.4 months (ependymoma); two patients achieved a partial response. CONCLUSIONS: Repeated ICV B7-H3 CAR T cell dosing is feasible and tolerable across a spectrum of pediatric CNS tumors, supporting continued investigation in future trials.
2026-06-30 | High-dose chemotherapy with autologous stem cell rescue in children under 5 years of age with central nervous system embryonal tumors: results from a prospective cohort in an upper-middle-income country
PURPOSE: High-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) has been employed to mitigate the long-term side effects of radiotherapy and improve survival outcomes in infants with embryonal central nervous system (CNS) tumors. METHODS: This prospective study, supported by federal funding from the National Oncological Care Support Program, included children younger than 5 years of age with newly diagnosed CNS embryonal tumors treated with surgery and HDCT/ASCR. RESULTS: Between 2016 and 2019, 36 patients were included: 22 with medulloblastoma (MB) and 14 with other CNS embryonal tumors. In the MB cohort, the mean age was 2.5 years, 13 were male. Gross total resection (GTR) was achieved in 18 patients; 15 had non-metastatic disease (M0). Among non-MB patients, the mean age was 2.7 years, 11 were female. Nine patients had GTR; 12 had M0. According to the MB molecular subgroup, the 2- and 5-year event-free survival (EFS) rates for the SHH subgroup were 76.9%, and overall survival (OS) was 92.3%. For the non-WNT/non-SHH subgroup, the 2- and 5-year EFS rates were 33.3% and 22.2%, and OS, 66.7% and 55.6%, respectively. Two SHH and five non-WNT/non-SHH patients were successfully salvaged with craniospinal irradiation after a mean of 12 months (range, 7-36 months). Among non-MB patients, the 2- and 5-year EFS and OS were 28.6/19.0% and 42.9/32.1%, respectively. All patients developed grade 3-4 mucositis/typhlitis and febrile neutropenia and 13.9% invasive fungal infections during HDCT. CONCLUSION: HDCT/ASCR is feasible in a middle-income country setting and provides favorable outcomes in SHH medulloblastoma. However, prognosis remains poor for non-SHH MB and other embryonal tumors, highlighting the need for novel molecularly guided therapies.
2026-06-24 | Guidance for the Diagnosis and Treatment of Rare Embryonal and Sarcomatous Brain Tumors—a Report from the Central Nervous System-International Registry for Rare Embryonal and Sarcomatous Tumors German Society of Pediatric Oncology and Hematology Study Group
Abstract: With the advent of multi-omic molecular profiling techniques, central nervous system tumor types previously not recognized by conventional neuropathological assessment have emerged, particularly among tumors formerly termed as "CNS- primitive neuroectodermal tumors." Given the diverse histopathological, molecular, radiological, and clinical characteristics of these tumors, diagnostic approaches and treatment strategies need to be adapted to our increasing knowledge. The small number of patients per year for individual tumor types precludes large cohort studies and mandates international cooperation and harmonization. To this end, the SIOPE Brain Tumor Group together with the European Reference Network for Pediatric Cancers has published the European Standards of Clinical Practice guidelines for rare embryonal and sarcomatous tumors.
2026-06-23 | ID #744 Epidemiological profile of central nervous system tumors in patients followed at the neuro-oncology outpatient clinic of ITACI (1994-2025)
Abstract Introduction Central nervous system (CNS) tumors are a major cause of morbidity and mortality in children and adolescents, often leading to neurological sequelae and reduced quality of life. In Brazil, epidemiological data from specialized centers remain scarce, limiting public health planning. The Instituto de Tratamento do Câncer Infantil (ITACI) is a national reference center in pediatric oncology. This study aimed to describe the epidemiological profile of CNS tumors treated at ITACI. Methods This retrospective, descriptive study analyzed the institutional database of the ITACI neuro-oncology outpatient clinic. All patients with confirmed CNS tumors followed between 1994 and 2025 were included. Variables analyzed were histological diagnosis and diagnostic frequency. Data were evaluated using descriptive statistics and expressed as absolute and relative frequencies. Results A total of 468 patients were analyzed, with slight male predominance (52.78%; n = 247). There was a progressive increase in diagnoses over time, with higher frequencies in recent years, especially 2025 (13.68%) and 2023 (12.61%). The category “Others”, grouping rare tumors, represented the most frequent diagnosis (18.80%; n = 88), reflecting the heterogeneity of CNS neoplasms. Among specific tumors, medulloblastoma was most prevalent (17.52%; n = 82), followed by pilocytic astrocytoma (11.54%; n = 54), low-grade gliomas (7.69%; n = 36), ependymomas (6.62%; n = 31), and germ cell tumors (5.77%; n = 27). Other relevant diagnoses included optic pathway gliomas, craniopharyngiomas, diffuse brainstem gliomas, and high-grade gliomas. Conclusion The study demonstrated an epidemiological pattern consistent with the literature, with predominance of embryonal and glial tumors and slight male predominance. The high frequency of rare tumors highlights the importance of specialized centers for accurate diagnosis and management. These findings reinforce ITACI’s role as a national reference center and contribute to Brazilian epidemiological data, supporting healthcare planning and public policy development in pediatric neuro-oncology.
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Drug Discovery Landscape
1 orphan drug designation for Central nervous system embryonal tumor.
1 orphan drug designation for Central nervous system embryonal tumor.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
genetically engineered herpes simplex virus | gene therapies | FDA | 2019-05-09 | — | Aettis, Inc. |
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