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Chromosomal anomalies and prognostic markers for intracranial and spinal ependymomas.

ABSTRACT: Ependymomas are neoplasms that can occur anywhere along the craniospinal axis. They are the third most common brain tumor in children, representing 10% of pediatric intracranial tumors, 4% of adult brain tumors, and 15% of all spinal cord tumors. As the heterogeneity of ependymomas has severely limited the prognostic value of the World Health Organization grading system, numerous studies have focused on genetic alterations as a potential basis for classification and prognosis. However, this endeavor has proven difficult due to variations of findings depending on tumor location, tumor grade, and patient age. While many have evaluated chromosomal abnormalities for ependymomas as a whole group, others have concentrated their efforts on specific subsets of populations. Here, we review modern findings of chromosomal analyses, their relationships with various genes, and their prognostic implications for intracranial and spinal cord ependymomas.

SUBMITTER: Yang I

PROVIDER: S-EPMC3615711 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Chromosomal anomalies and prognostic markers for intracranial and spinal ependymomas.

Yang Isaac I Nagasawa Daniel T DT Kim Won W Spasic Marko M Trang Andy A Lu Daniel C DC Martin Neil A NA

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 20120418 6

Ependymomas are neoplasms that can occur anywhere along the craniospinal axis. They are the third most common brain tumor in children, representing 10% of pediatric intracranial tumors, 4% of adult brain tumors, and 15% of all spinal cord tumors. As the heterogeneity of ependymomas has severely limited the prognostic value of the World Health Organization grading system, numerous studies have focused on genetic alterations as a potential basis for classification and prognosis. However, this ende ...[more]

PMID: 22516549

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Project description:Based on DNA-methylation, ependymomas growing in the spinal cord comprise two major molecular types termed spinal (SP-EPN) and myxopapillary ependymomas (MPE(-A/B)), which differ with respect to their clinical features and prognosis. Due to the existing discrepancy between histomorphogical diagnoses and classification using methylation data, we asked whether deep neural networks can predict the DNA methylation class of spinal cord ependymomas from hematoxylin and eosin stained whole-slide images. Using explainable AI, we further aimed to prospectively improve the consistency of histology-based diagnoses with DNA methylation profiling by identifying and quantifying distinct morphological patterns of these molecular ependymoma types. We assembled a case series of 139 molecularly characterized spinal cord ependymomas (nMPE = 84, nSP-EPN = 55). Self-supervised and weakly-supervised neural networks were used for classification. We employed attention analysis and supervised machine-learning methods for the discovery and quantification of morphological features and their correlation to the diagnoses of experienced neuropathologists. Our best performing model predicted the DNA methylation class with 98% test accuracy and used self-supervised learning to outperform pretrained encoder-networks (86% test accuracy). In contrast, the diagnoses of neuropathologists matched the DNA methylation class in only 83% of cases. Domain-adaptation techniques improved model generalization to an external validation cohort by up to 22%. Statistically significant morphological features were identified per molecular type and quantitatively correlated to human diagnoses. The approach was extended to recently defined subtypes of myxopapillary ependymomas (MPE-(A/B), 80% test accuracy). In summary, we demonstrated the accurate prediction of the DNA methylation class of spinal cord ependymomas (SP-EPN, MPE(-A/B)) using hematoxylin and eosin stained whole-slide images. Our approach may prospectively serve as a supplementary resource for integrated diagnostics and may even help to establish a standardized, high-quality level of histology-based diagnostics across institutions-in particular in low-income countries, where expensive DNA-methylation analyses may not be readily available.

Project description:Background contextLaboratory values have been found to be useful predictive measures of survival following surgery. The utility of laboratory values for prognosticating outcomes among patients with spinal metastases has not been studied.PurposeTo determine the prognostic capacity of laboratory values at presentation including white blood cell count, serum albumin and platelet-lymphocyte ratio (PLR) in patients with spinal metastases.Study designRetrospective review of records from two tertiary care centers (2005-2017).Patient samplePatients, aged 40 to 80, who received operative or nonoperative management for spinal metastases.Outcome measuresSurvival, complications, or hospital readmissions within 90 days of treatment and a composite measure for treatment failure accounting for changes in ambulatory function and mortality at 6 months following presentation.MethodsMultivariable Cox proportional hazard regression analysis was used to analyze the relationship between laboratory values and length of survival, adjusting for confounders. Multivariable logistic regression was used in analyses related to 6-month and 1-year mortality, complications, readmissions, and treatment failure. A scoring rubric was developed based on the performance of laboratory values in the multivariable tests. Internal validation was performed using a bootstrap simulation that consisted of sampling with replacement and 1,000 replications.ResultsWe included 1,216 patients. Thirty-seven percent of patients received a surgical intervention and 63% were treated nonoperatively. Median survival for the cohort as a whole was 255 days (interquartile range 93-642 days). The PLR (hazard ratio [HR] 1.53; 95% confidence interval [CI] 1.29, 1.80; p<.001) and albumin (HR 0.54; 95% CI 0.45, 0.64; p<.001) were significantly associated with survival, whereas WBC count (HR 1.08; 95% CI 0.86, 1.36; p=.50) was not associated with this outcome. Similar findings were encountered for 6-month and 1-year mortality as well as the composite measure for treatment failure. The PLR and albumin performed well in our scoring rubric and findings were preserved in the bootstrapping validation.ConclusionsIndividuals with low serum albumin and elevated PLR should be advised regarding the impact of these laboratory markers on outcomes including survival, irrespective of treatments received. An effort should also be made to optimize nutrition and PLR, if practicable, before treatment to minimize the potential for development of adverse events.

Dataset Information

Chromosomal anomalies and prognostic markers for intracranial and spinal ependymomas.

Publications

Chromosomal anomalies and prognostic markers for intracranial and spinal ependymomas.

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