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Primary spinal anaplastic ependymoma: A single-institute retrospective cohort and systematic review.Frontiers in Oncology 2023Primary spinal anaplastic ependymoma (PSAE) is an extremely rare disease. We aim to report the largest PSAE cohort, evaluate the treatments, and investigate the...
OBJECTIVE
Primary spinal anaplastic ependymoma (PSAE) is an extremely rare disease. We aim to report the largest PSAE cohort, evaluate the treatments, and investigate the prognostic factors for progression-free survival (PFS).
METHODS
Clinical data collected from the authors' institute and literature articles were pooled and described. Survival analysis and multivariable Cox regression analysis were performed to evaluate therapies and investigate prognostic factors for PFS.
RESULTS
Our cohort included 22 females and 16 males, with a median age of 33 years. PSAE developed mostly on cervical and cervicothoracic levels. The median length measured 3 segments. Half of PSAE were intramedullary. Pain was the most common symptom. The median duration of symptoms was 6 months. Neurological statuses were improved in 76% following treatments, whereas clinical tumor progression occurred in 41.7%. The estimated median progression-free survival was 132 months, and the estimated median survival was 192 months. The median Ki-67 index was 15%. Patients aged less than or equal to 25 experienced worse neurological statuses and more repeated progression. Age less than or equal to 25 (HR 10.312, 95%CI 1.535-69.260, p=0.016), gross total resection (HR 0.116, 95%CI 0.020-0.688, p=0.018), and radiotherapy (HR 0.084, 95%CI 0.009-0.804, p=0.032) are three prognostic factors for tumor progression.
CONCLUSION
Tumor progression remains a big concern in the clinical course of PSAE. Being aged above 25, undergoing GTR, and accepting adjuvant radiotherapy put patients at lower risk for tumor progression. Younger patients might have worse neurological statuses compared with those aged over 25.
PubMed: 36824145
DOI: 10.3389/fonc.2023.1083085 -
Pediatric Neurosurgery 2023Ependymoma is one of the most common malignant pediatric brain tumors and can be difficult to treat. Over the last decade, much progress has been made in the... (Review)
Review
BACKGROUND
Ependymoma is one of the most common malignant pediatric brain tumors and can be difficult to treat. Over the last decade, much progress has been made in the understanding of the underlying molecular drivers within this group of tumors, but clinical outcomes remain unchanged.
SUMMARY
Here, we review the most recent molecular advances in pediatric ependymoma, evaluate results of recent clinical trials and discuss the ongoing challenges in the field and questions that remain.
KEY MESSAGES
The field of ependymoma has vastly changed over the last several decades with ten distinct molecular subgroups now described, but much progress needs to be made in developing new therapeutic strategies and targets.
Topics: Child; Humans; Ependymoma; Brain Neoplasms
PubMed: 37231859
DOI: 10.1159/000530868 -
Radiologie (Heidelberg, Germany) Aug 2023Tumors of the posterior fossa account for about 50-55% of brain tumors in childhood. (Review)
Review
CLINICAL ISSUE
Tumors of the posterior fossa account for about 50-55% of brain tumors in childhood.
DIAGNOSTIC WORKUP
The most frequent tumor entities are medulloblastomas, pilocytic astrocytomas, ependymomas, diffuse midline gliomas and atypical teratoid-rhabdoid tumors. Neuroradiological differential diagnosis with magnetic resonance imaging (MRI) is of considerable importance for preoperative planning as well as planning of follow-up therapy.
PERFORMANCE
Most important findings for differential diagnosis of pediatric posterior fossa tumors are tumor location, patient age and the intratumoral apparent diffusion assessed by diffusion-weighted imaging.
ACHIEVEMENTS
Advanced MR techniques like MRI perfusion and MR spectroscopy can be helpful both in the initial differential diagnosis and in tumor surveillance, but exceptional characteristics of certain tumor entities should be kept in mind.
PRACTICAL RECOMMENDATIONS
Standard clinical MRI sequences including diffusion-weighted imaging are the main diagnostic tool in evaluating posterior fossa tumors in children. Advanced imaging methods can be helpful, but should never be interpreted separately from conventional MRI sequences.
Topics: Child; Humans; Medulloblastoma; Infratentorial Neoplasms; Brain Neoplasms; Magnetic Resonance Imaging; Cerebellar Neoplasms
PubMed: 37306749
DOI: 10.1007/s00117-023-01159-y -
Children (Basel, Switzerland) Apr 2022Brain tumors are the most common solid tumors in children and are associated with high mortality. The most common childhood brain tumors are grouped as low-grade gliomas... (Review)
Review
Brain tumors are the most common solid tumors in children and are associated with high mortality. The most common childhood brain tumors are grouped as low-grade gliomas (LGG), high grade gliomas (HGG), ependymomas, and embryonal tumors, according to the World Health Organization (WHO). Advances in molecular genetics have led to a shift from pure histopathological diagnosis to integrated diagnosis. For the first time, these new criteria were included in the WHO classification published in 2016 and has been further updated in the 2021 edition. Integrated diagnosis is based on molecular genomic similarities of the tumor subclasses, and it can better explain the differences in clinical courses of previously histopathologically identical entities. Important advances have also been made in pediatric neuro-oncology. A growing understanding of the molecular-genetic background of tumorigenesis has improved the diagnostic accuracy. Re-stratification of treatment protocols and the development of targeted therapies will significantly affect overall survival and quality of life. For some pediatric tumors, these advances have significantly improved therapeutic management and prognosis in certain tumor subgroups. Some therapeutic approaches also have serious long-term consequences. Therefore, optimized treatments are greatly needed. Here, we discuss the importance of multidisciplinary collaboration and the role of (pediatric) neurosurgery by briefly describing the most common childhood brain tumors and their currently recognized molecular subgroups.
PubMed: 35455542
DOI: 10.3390/children9040498 -
Cancers Dec 2021Ependymoma is a biologically diverse tumor wherein molecular classification has superseded traditional histological grading based on its superior ability to characterize... (Review)
Review
Ependymoma is a biologically diverse tumor wherein molecular classification has superseded traditional histological grading based on its superior ability to characterize behavior, prognosis, and possible targeted therapies. The current, updated molecular classification of ependymoma consists of ten distinct subgroups spread evenly among the spinal, infratentorial, and supratentorial compartments, each with its own distinct clinical and molecular characteristics. In this review, the history, histopathology, standard of care, prognosis, oncogenic drivers, and hypothesized molecular targets for all subgroups of ependymoma are explored. This review emphasizes that despite the varied behavior of the ependymoma subgroups, it remains clear that research must be performed to further elucidate molecular targets for these tumors. Although not all ependymoma subgroups are oncologically aggressive, development of targeted therapies is essential, particularly for cases where surgical resection is not an option without causing significant morbidity. The development of molecular therapies must rely on building upon our current understanding of ependymoma oncogenesis, as well as cultivating transfer of knowledge based on malignancies with similar genomic alterations.
PubMed: 34944845
DOI: 10.3390/cancers13246218 -
Journal of Neuropathology and... Feb 2023The MYB/MYBL1::QKI fusion induces the protooncogene, MYB, and deletes the tumor suppressor gene, QKI. MYB/MYBL1::QKI rearrangement was previously reported only in... (Review)
Review
The MYB/MYBL1::QKI fusion induces the protooncogene, MYB, and deletes the tumor suppressor gene, QKI. MYB/MYBL1::QKI rearrangement was previously reported only in angiocentric glioma (AG) and diffuse low-grade glioma. This report compares 2 tumors containing the MYB/MYBL1::QKI fusion: a diffuse pediatric-type high-grade glioma (DPedHGG) in an 11-year-old boy and an AG in a 46-year-old woman. We used immunohistochemistry, next-generation sequencing, and methylation profiling to characterize each tumor and compare our findings to the literature on AG and tumors with the MYB/MYBL1::QKI rearrangement. Both tumors were astrocytic with angiocentric patterns. The MYB::QKI fusion-positive DPedHGG, which recurred once, was accompanied by TP53 mutation and amplification of CDK6 and KRAS, suggesting malignant transformation secondary to additional genetic aberrations. The second case was the adult AG with MYBL1::QKI fusion, which mimicked ependymoma based on histopathology and its dot- and ring-like epithelial membrane antigen positivity. Combined with a literature review, our results suggest that MYB/MYBL1 alterations are not limited to low-grade gliomas, including AG. AG is most common in the cerebra of children and adolescents but exceptional cases occur in adults and the acquisition of additional genetic mutations may contribute to high-grade glioma. These cases further demonstrate that molecular characteristics, morphologic features, and clinical context are essential for diagnosis.
Topics: Male; Adult; Female; Adolescent; Humans; Child; Middle Aged; Neoplasm Recurrence, Local; Glioma; Mutation; Ependymoma; Brain Neoplasms; Proto-Oncogene Proteins; Trans-Activators; RNA-Binding Proteins
PubMed: 36592415
DOI: 10.1093/jnen/nlac123 -
Neuroradiology Sep 2022Subependymomas located within the 4th ventricle are rare, and the literature describing imaging characteristics is sparse. Here, we describe the clinical and... (Review)
Review
PURPOSE
Subependymomas located within the 4th ventricle are rare, and the literature describing imaging characteristics is sparse. Here, we describe the clinical and radiological characteristics of 29 patients with 4th ventricle subependymoma.
METHODS
This is a retrospective multi-center study performed after Institutional Review Board (IRB) approval. Patients diagnosed with suspected 4th ventricle subependymoma were identified. A review of clinical, radiology, and pathology reports along with magnetic resonance imaging (MRI) images was performed.
RESULTS
Twenty-nine patients, including 6 females, were identified. Eighteen patients underwent surgery with histopathological confirmation of subependymoma. The median age at diagnosis was 52 years. Median tumor volume for the operative cohort was 9.87 cm, while for the non-operative cohort, it was 0.96 cm. Thirteen patients in the operative group exhibited symptoms at diagnosis. For the total cohort, the majority of subependymomas (n = 22) were isointense on T1, hyperintense (n = 22) on T2, and enhanced (n = 24). All tumors were located just below the body of the 4th ventricle, terminating near the level of the obex. Fourteen cases demonstrated extension of tumor into foramen of Magendie or Luschka.
CONCLUSION
To the best of our knowledge, this is the largest collection of 4th ventricular subependymomas with imaging findings reported to date. All patients in this cohort had tumors originating between the bottom of the body of the 4th ventricle and the obex. This uniform and specific site of origin aids with imaging diagnosis and may infer possible theories of origin.
Topics: Female; Fourth Ventricle; Glioma, Subependymal; Humans; Magnetic Resonance Imaging; Multicenter Studies as Topic; Radiography; Tumor Burden
PubMed: 35426054
DOI: 10.1007/s00234-022-02944-7 -
Neuro-oncology Jun 2022SIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) of non-metastatic intracranial ependymoma in children aged 3-21 years... (Clinical Trial)
Clinical Trial
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 3-21 years treated with a staged management strategy. A further aim was to assess the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide, and cyclophosphamide (VEC). We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers.
METHODS
Seventy-four participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation, 1q, hTERT, ReLA, Tenascin-C, H3K27me3, and pAKT status were evaluated.
RESULTS
Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. GTR was achieved in 33/74 (44.6%) and associated with improved EFS (P = .003, HR = 2.6, 95% confidence interval (CI) 1.4-5.1). Grade 3 tumours were associated with worse OS (P = .005, HR = 2.8, 95%CI 1.3-5.8). 1q gain and hTERT expression were associated with poorer EFS (P = .003, HR = 2.70, 95%CI 1.49-6.10 and P = .014, HR = 5.8, 95%CI 1.2-28) and H3K27me3 loss with worse OS (P = .003, HR = 4.6, 95%CI 1.5-13.2). Methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, best chemotherapy RR was 65.5% (19/29, 95%CI 45.7-82.1), exceeding the prespecified 45%.
CONCLUSIONS
Participants with totally resected ependymoma had the best outcomes. RR of STR to VEC exceeded the pre-specified efficacy criterion. However, cases of inaccurate stratification highlighted the need for rapid central review. 1q gain, H3K27me3 loss, and hTERT expression were all associated with poorer survival outcomes.
Topics: Child; Chromosome Aberrations; Cyclophosphamide; Ependymoma; Etoposide; Follow-Up Studies; Histones; Humans; Treatment Outcome; Vincristine
PubMed: 35018471
DOI: 10.1093/neuonc/noac012 -
Cureus Oct 2021We present the case of a 29-year-old patient whose pain began with the interscapular region, progressing to paresthesia and loss of muscle strength in the lower...
We present the case of a 29-year-old patient whose pain began with the interscapular region, progressing to paresthesia and loss of muscle strength in the lower extremities. MRI of the spine was done, a lesion was found in T2 to T6, ependymoma was suspected and was taken to subtotal resection with laminectomy, the histopathological report, as well as the immunohistochemistry, was compatible with glioblastoma type not otherwise specified (NOS). He received adjuvant with radiotherapy and concomitant chemotherapy, but he progressed to the cervical and lumbar spine, the patient died 16 months after diagnosis. A review of the literature is made and the clinical and radiological characteristics and treatment protocols that have been used in this entity are reported.
PubMed: 34754630
DOI: 10.7759/cureus.18464 -
Neuro-oncology Jul 2023A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain...
BACKGROUND
A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas.
METHODS
Tumors diagnosed as intracranial ependymomas from 170 adult patients collected from 8 diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were correlated with progression-free survival (PFS).
RESULTS
The classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6%, and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE, and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (GTR) (P = .009) and postoperative radiotherapy (P = .007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of the prognosis within molecularly defined ependymoma classes.
CONCLUSIONS
DNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. GTR and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.
Topics: Adult; Humans; Retrospective Studies; DNA Methylation; Prognosis; Brain Neoplasms; Ependymoma
PubMed: 36734226
DOI: 10.1093/neuonc/noad030