Recent Advances in the Classification and Treatment of Ependymomas

Abstract

Ependymomas are a subgroup of ependymal glia-derived neoplasms that affect children as well as adults. Arising within any CNS compartment, symptoms at presentation can range from acute onset due to increased intracranial pressure to insidious myelopathy. The overall survival (OS) outcomes in adult patients across the subgroups is heterogeneous with subependymoma having an excellent prognosis often even in the absence of any treatment, whereas supratentorial ependymomas tend to be higher grade in nature and may have an OS of 5 years despite gross total resection and adjuvant radiation. The rarity of ependymal tumors, together still only representing 1.8% of all primary CNS tumors, has been a long-standing challenge in defining optimal treatment guidelines via prospective randomized trials. Retrospective studies have supported maximal safe resection, ideally gross total resection, as the optimal treatment with adjuvant radiation therapy proffering additional tumor control. The evidence for efficacy of chemotherapy and targeted agents in adult ependymomas is minimal. Recent investigations of the molecular, genetic, and DNA methylation profiles of ependymal tumors across all age groups and CNS compartments have identified distinct oncogenic gene products as well as nine molecular subgroups correlating with similar outcomes. The 2016 World Health Organization of Tumors of the Central Nervous System update addresses some of these findings, although their clinical significance has not yet been fully validated. There are inconsistent survival outcomes in retrospective studies for ependymomas graded as II versus III, bringing into question the validity of histologic grading which is subject to high interobserver variability in part due to inconsistent application of mitotic count parameters.

Molecular Classification and Therapeutic Targets in Ependymoma

“…PF-SE carries low pathogenicity and, in fact, is often not discovered until postmortem examination [ 64 , 65 ]. GTR is generally thought to be curative, though recurrences can occur [ 62 , 66 ]. Radiotherapy may be used in cases of STR, but is typically reserved as salvage therapy if progression occurs.…”

MicroRNA expression in pediatric intracranial ependymomas and their potential value for tumor grading

“…This result underlines the fact that miRNA are pluripotent molecules and their role in tumorigenesis in given tumor type needs to be elucidated by more studies especially in tumors of genetically heterogeneous nature. Tumor grading in ependymoma reveals high interindividual variability (19). This fact calls for new markers which would make distinguishing between low-grade and high-grade lesion more convenient.…”

Treatment Decisions of World Health Organization Grade II and III Ependymomas in Molecular Era

“…Interestingly, it has been reported that the level of resection does not significantly affect the outcome within the STEPN- RELA -positive subgroup in a retrospective analysis for patient samples collected over a long period of time over 20 years [ 25 ]. ST-EPN- YAP1 subgroup is associated with favorable clinical outcome [ 13 , 15 ]. Clinical trials with de-escalating therapy could be recommended for this subgroup.…”