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Neuro-oncology Jun 2022The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is...
BACKGROUND
The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB.
METHODS
We extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers.
RESULTS
For all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (P < .0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (P = .002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86.
CONCLUSIONS
We present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy.
Topics: Ependymoma; Humans; Machine Learning; Magnetic Resonance Imaging; Prognosis; Retrospective Studies
PubMed: 34850171
DOI: 10.1093/neuonc/noab272 -
Journal of Applied Clinical Medical... Jan 2024To study the dosimetric impact of incorporating variable relative biological effectiveness (RBE) of protons in optimizing intensity-modulated proton therapy (IMPT)...
PURPOSE
To study the dosimetric impact of incorporating variable relative biological effectiveness (RBE) of protons in optimizing intensity-modulated proton therapy (IMPT) treatment plans and to compare it with conventional constant RBE optimization and linear energy transfer (LET)-based optimization.
METHODS
This study included 10 pediatric ependymoma patients with challenging anatomical features for treatment planning. Four plans were generated for each patient according to different optimization strategies: (1) constant RBE optimization (ConstRBEopt) considering standard-of-care dose requirements; (2) LET optimization (LETopt) using a composite cost function simultaneously optimizing dose-averaged LET (LET ) and dose; (3) variable RBE optimization (VarRBEopt) using a recent phenomenological RBE model developed by McNamara et al.; and (4) hybrid RBE optimization (hRBEopt) assuming constant RBE for the target and variable RBE for organs at risk. By normalizing each plan to obtain the same target coverage in either constant or variable RBE, we compared dose, LET , LET-weighted dose, and equivalent uniform dose between the different optimization approaches.
RESULTS
We found that the LETopt plans consistently achieved increased LET in tumor targets and similar or decreased LET in critical organs compared to other plans. On average, the VarRBEopt plans achieved lower mean and maximum doses with both constant and variable RBE in the brainstem and spinal cord for all 10 patients. To compensate for the underdosing of targets with 1.1 RBE for the VarRBEopt plans, the hRBEopt plans achieved higher physical dose in targets and reduced mean and especially maximum variable RBE doses compared to the ConstRBEopt and LETopt plans.
CONCLUSION
We demonstrated the feasibility of directly incorporating variable RBE models in IMPT optimization. A hybrid RBE optimization strategy showed potential for clinical implementation by maintaining all current dose limits and reducing the incidence of high RBE in critical normal tissues in ependymoma patients.
Topics: Child; Humans; Proton Therapy; Radiotherapy Dosage; Relative Biological Effectiveness; Linear Energy Transfer; Ependymoma; Radiotherapy Planning, Computer-Assisted; Organs at Risk
PubMed: 37985962
DOI: 10.1002/acm2.14207 -
Scientific Reports Jan 2024Spinal myxopapillary ependymoma (MPE) and schwannoma represent clinically distinct intradural extramedullary tumors, albeit with shared and overlapping magnetic...
Spinal myxopapillary ependymoma (MPE) and schwannoma represent clinically distinct intradural extramedullary tumors, albeit with shared and overlapping magnetic resonance imaging (MRI) characteristics. We aimed to identify significant MRI features that can differentiate between MPE and schwannoma and develop a novel prediction model using these features. In this study, 77 patients with MPE (n = 24) or schwannoma (n = 53) who underwent preoperative MRI and surgical removal between January 2012 and December 2022 were included. MRI features, including intratumoral T2 dark signals, subarachnoid hemorrhage (SAH), leptomeningeal seeding, and enhancement patterns, were analyzed. Logistic regression analysis was conducted to distinguish between MPE and schwannomas based on MRI parameters, and a prediction model was developed using significant MRI parameters. The model was validated internally using a stratified tenfold cross-validation. The area under the curve (AUC) was calculated based on the receiver operating characteristic curve analysis. MPEs had a significantly larger mean size (p = 0.0035), higher frequency of intratumoral T2 dark signals (p = 0.0021), associated SAH (p = 0.0377), and leptomeningeal seeding (p = 0.0377). Focal and diffuse heterogeneous enhancement patterns were significantly more common in MPEs (p = 0.0049 and 0.0038, respectively). Multivariable analyses showed that intratumoral T2 dark signal (p = 0.0439) and focal (p = 0.0029) and diffuse enhancement patterns (p = 0.0398) were independent factors. The prediction model showed an AUC of 0.9204 (95% CI 0.8532-0.9876) and the average AUC for internal validation was 0.9210 (95% CI 0.9160-0.9270). MRI provides useful data for differentiating spinal MPEs from schwannomas. The prediction model developed based on the MRI features demonstrated excellent discriminatory performance.
Topics: Humans; Diagnosis, Differential; Spinal Cord Neoplasms; Neurilemmoma; Spine; Magnetic Resonance Imaging; Ependymoma; Retrospective Studies
PubMed: 38167614
DOI: 10.1038/s41598-023-50806-w -
Scientific Reports Dec 2019Intramedullary spinal cord tumors (IMSCTs) are rare neoplasms that have limited treatment options and are associated with high rates of morbidity and mortality. To...
Intramedullary spinal cord tumors (IMSCTs) are rare neoplasms that have limited treatment options and are associated with high rates of morbidity and mortality. To better understand the genetic basis of these tumors we performed whole exome sequencing on 45 tumors and matched germline DNA, including twenty-nine spinal cord ependymomas and sixteen astrocytomas. Though recurrent somatic mutations in IMSCTs were rare, we identified NF2 mutations in 15.7% of tumors (ependymoma, N = 7; astrocytoma, N = 1), RP1 mutations in 5.9% of tumors (ependymoma, N = 3), and ESX1 mutations in 5.9% of tumors (ependymoma, N = 3). We further identified copy number amplifications in CTU1 in 25% of myxopapillary ependymomas. Given the paucity of somatic driver mutations, we further performed whole-genome sequencing of 12 tumors (ependymoma, N = 9; astrocytoma, N = 3). Overall, we observed that IMSCTs with intracranial histologic counterparts (e.g. glioblastoma) did not harbor the canonical mutations associated with their intracranial counterparts. Our findings suggest that the origin of IMSCTs may be distinct from tumors arising within other compartments of the central nervous system and provides the framework to begin more biologically based therapeutic strategies.
Topics: Adolescent; Adult; Aged; Astrocytoma; Ependymoma; Female; Genomics; Glioblastoma; Glioma; Homeodomain Proteins; Humans; Male; Microtubule-Associated Proteins; Middle Aged; Neurofibromin 2; Spinal Cord; Spinal Cord Neoplasms; Exome Sequencing
PubMed: 31822682
DOI: 10.1038/s41598-019-54286-9 -
British Journal of Cancer Jan 2007Ependymomas are tumours that arise throughout the central nervous system. Little is known regarding the aberrant cellular and molecular processes that generate these... (Review)
Review
Ependymomas are tumours that arise throughout the central nervous system. Little is known regarding the aberrant cellular and molecular processes that generate these tumours. This lack of knowledge has hampered efforts to reduce the significant mortality and morbidity that are associated with ependymoma. Here, we review recent data that suggest that radial glia are cells of origin of ependymoma, and discuss the processes that might transform these neural progenitors into ependymoma cancer stem cells.
Topics: Brain Neoplasms; Cell Transformation, Neoplastic; Central Nervous System Neoplasms; Ependymoma; Humans; Models, Biological; Neoplastic Stem Cells; Neuroglia; Signal Transduction
PubMed: 17179988
DOI: 10.1038/sj.bjc.6603519 -
The Journal of Medical Investigation :... 2014We present a rare case of acute onset cauda equina syndrome caused by a ruptured myxopapillary ependymoma with accompanying hemorrhage. A 26-year-old healthy woman... (Review)
Review
We present a rare case of acute onset cauda equina syndrome caused by a ruptured myxopapillary ependymoma with accompanying hemorrhage. A 26-year-old healthy woman developed muscle weakness and sensory disturbances in her bilateral lower extremities. Magnetic resonance imaging showed a huge mass from the L1 body to the L2-3 disc level. She was able to ambulate with crutches after the tumor was successfully removed. To prevent recurrence, she received whole brain and spinal cord radiation. No sing of recurrence were detected at the 8 month follow up.
Topics: Adult; Cauda Equina; Ependymoma; Female; Hemorrhage; Humans; Peripheral Nervous System Neoplasms; Rupture, Spontaneous
PubMed: 25264068
DOI: 10.2152/jmi.61.430 -
Acta Neuropathologica Mar 2021Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by the presence of either a C11orf95-RELA or a...
Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by the presence of either a C11orf95-RELA or a YAP-MAMLD1 fusion, respectively. There is growing evidence that supratentorial ependymomas without these genetic features exist. In this study, we report on 18 pediatric non-RELA/non-YAP supratentorial ependymomas that were systematically characterized by means of their histology, immunophenotype, genetics, and epigenomics. Comprehensive molecular analyses included high-resolution copy number analysis, methylation profiling, analysis of fusion transcripts by Nanostring technology, and RNA sequencing. Based upon histological and immunohistochemical features two main patterns were identified-RELA-like (n = 9) and tanycytic ependymomas (n = 6). In the RELA-like group histologically assigned to WHO grade III and resembling RELA-fused ependymomas, tumors lacked nuclear expression of p65-RelA as a surrogate marker for a pathological activation of the NF-κB pathway. Three tumors showed alternative C11orf95 fusions to MAML2 or NCOA1. A methylation-based brain tumor classifier assigned two RELA-like tumors to the methylation class "EP, RELA-fusion"; the others demonstrated no significant similarity score. Of the tanycytic group, 5/6 tumors were assigned a WHO grade II. No gene fusions were detected. Methylation profiling did not show any association with an established methylation class. We additionally identified two astroblastoma-like tumors that both presented with chromothripsis of chromosome 22 but lacked MN1 breaks according to FISH analysis. They revealed novel fusion events involving genes in chromosome 22. One further tumor with polyploid cytogenetics was interpreted as PFB ependymoma by the brain tumor methylation classifier but had no relation to the posterior fossa. Clinical follow-up was available for 16/18 patients. Patients with tanycytic and astroblastoma-like tumors had no relapse, while 2 patients with RELA-like ependymomas died. Our data indicate that in addition to ependymomas discovered so far, at least two more supratentorial ependymoma types (RELA-like and tanycytic) exist.
Topics: Adaptor Proteins, Signal Transducing; Adolescent; Child; Child, Preschool; Ependymoma; Female; Humans; Infant; Male; Supratentorial Neoplasms; Transcription Factor RelA; Transcription Factors; YAP-Signaling Proteins
PubMed: 33481105
DOI: 10.1007/s00401-020-02260-5 -
Turkish Neurosurgery 2024To identify ependymoma (EPN) driver genes and key pathways, and also to illuminate the connection between prognosis of EPN patients and expression levels of driver genes.
AIM
To identify ependymoma (EPN) driver genes and key pathways, and also to illuminate the connection between prognosis of EPN patients and expression levels of driver genes.
MATERIAL AND METHODS
The gene expression profiles of GSE50161, GSE66354, GSE74195, and GSE86574 were analyzed to figure out the differentially expressed genes (DEGs) between tissue of EPN and normal brain samples. To harvest the enrichment functions, pathways and hub genes, the Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction (PPI) network analysis were made. Subsquently, survival analysis was performed in 325 patients to illuminate the connection between prognosis of EPN and expression levels of hub genes.
RESULTS
20 functions and 10 pathways which were up- or downregulated between the EPN and normal samples were revealed applying GO and KEGG analysis. Mutual hub genes were TP53, TOP2A, CDK1, PCNA, and ACTA2. The pathways of Hedgehog and notch signaling, mismatch repair (MMR), and retrograde endocannabinoid were significantly abnormally regulated in EPN tissue. Survival analysis revealed favorable progression-free (PFS) and overall (OS) survival in EPN patients with low expression of TOP2A, CDK1, PCNA, and ACTA2 (p < 0.05).
CONCLUSION
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.
Topics: Humans; Proliferating Cell Nuclear Antigen; Brain; DNA Mismatch Repair; Ependymoma; Gene Expression
PubMed: 30649797
DOI: 10.5137/1019-5149.JTN.21876-17.5 -
Asian Spine Journal Dec 2014Myxopapillary ependymoma in childhood typically occurs in the central nervous system. There are few surgical cases of myxopapillary ependymoma of the cauda equina in...
Myxopapillary ependymoma in childhood typically occurs in the central nervous system. There are few surgical cases of myxopapillary ependymoma of the cauda equina in children. We report a case of myxopapillary ependymoma of the cauda equina in a 5-year-old boy, who presented with leg pain and abnormal gait. Subtotal resection surgery was performed. Following the subtotal tumor resection, follow-up magnetic resonance imaging evaluation showed a recurrent tumor. As a result, we performed a second subtotal tumor resection and followed with postoperative radiation therapy. No further evidence of the disease has been noted elsewhere in the patient in over ten years of follow-up. Myxopapillary ependymoma of the cauda equina in a young boy was improved by subtotal tumor resection and postoperative radiation therapy.
PubMed: 25558331
DOI: 10.4184/asj.2014.8.6.846 -
Neuro-oncology Apr 2015Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the...
BACKGROUND
Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the outcome of patients with MPE treated with surgery, radiotherapy (RT), and/or chemotherapy.
METHODS
The medical records of 183 MPE patients (male: 59%) treated at the MD Anderson Cancer Center and 11 institutions from the Rare Cancer Network were retrospectively reviewed. Mean patient' age at diagnosis was 35.5 ± 15.8 years. Ninety-seven (53.0%) patients underwent surgery without RT, and 86 (47.0%) were treated with surgery and/or RT. Median RT dose was 50.4 Gy. Median follow-up was 83.9 months.
RESULTS
Fifteen (8.2%) patients died, 7 of unrelated cause. The estimated 10-year overall survival was 92.4% (95% CI: 87.7-97.1). Treatment failure was observed in 58 (31.7%) patients. Local failure, distant spinal relapse, and brain failure were observed in 49 (26.8%), 17 (9.3%), and 11 (6.0%) patients, respectively. The estimated 10-year progression-free survival was 61.2% (95% CI: 52.8-69.6). Age (<36 vs ≥36 y), treatment modality (surgery alone vs surgery and RT), and extent of surgery were prognostic factors for local control and progression-free survival on univariate and multivariate analysis.
CONCLUSIONS
In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.
Topics: Adult; Chemotherapy, Adjuvant; Disease-Free Survival; Ependymoma; Female; Humans; Male; Spinal Neoplasms; Treatment Outcome
PubMed: 25301811
DOI: 10.1093/neuonc/nou293