Distinct disease-risk groups in pediatric supratentorial and posterior fossa ependymomas

Abstract

Purpose No reliable classification exists for the therapeutic stratification of children with ependymoma, such that disease-risk might be identified and patients treated to ensure a combination of maximal cure rates and minimal adverse therapeutic effects. This study examined associations between clinicopathological and cytogenetic variables and outcome in a trial cohort of children with ependymoma, with the aim of defining a practical scheme for grading this heterogeneous tumor. Methods Intracranial ependymomas (n=146) from children treated on the RT1 trial at St. Jude Children’s Research Hospital were evaluated for the status of multiple pathological features. Interphase FISH (iFISH) defined the status of chromosomes 1q, 6q (LATS1), and 9p21 (CDKN2A). Data relating to these variables were compared with survival data in order to model disease-risk groups. Results Extent of surgical resection was a significant determinant of outcome. Tumor cell density and mitotic count were associated with outcome among children with posterior fossa ependymomas (n=119). Among pathologic factors, only brain invasion was associated with outcome in children with supratentorial ependymomas (n=27). Gain of 1q was independently associated with outcome and in combination with clinicopathological variables defined a three-tier system of disease-risk for posterior fossa tumors. Conclusions Among children developing posterior fossa ependymomas treated with maximal surgical resection and conformal radiotherapy, key clinicopathological variables and chromosome 1q status can be used to define tiers of disease-risk. In contrast, risk factors for pediatric supratentorial tumors are limited to subtotal resection and brain invasion.

Anaplastic Ependymomas, Report of 3 Pediatric Cases. Update on Molecular Markers - Risk Groups and Therapeutic Options

“…The WHO classification includes pathological variations of ependymoma grouped like this: grade I with Myxopapillary and subependymoma variant, the classic tumor grade II (clear cells, tanacitic and papillary variants) and grade III anaplastic type. There are reported differences between infratentorial and supratentorial ependymomas, it was observed that the pathological classification does not correlate with the anatomical location and the clinical results [1]. Relevant cytogenetic abnormalities found in anaplastic ependymomas (AE) are the 1q chromosome gain, anomalies in copies of chromosomes 6q25 (LATS1), 9p21 (CDKN2A), 11q.13 (generates the fusion protein C11ORF95-RELA).…”

“…Relevant cytogenetic abnormalities found in anaplastic ependymomas (AE) are the 1q chromosome gain, anomalies in copies of chromosomes 6q25 (LATS1), 9p21 (CDKN2A), 11q.13 (generates the fusion protein C11ORF95-RELA). A group was established that included patients with the following clinical-molecular profile: very young by age, recurrent tumor located in the posterior fossa and the 1q gain that is related -independently-with a worse prognosis and a strong predictor of adverse outcomes [1,2]. The alteration in the chromosomes 6q25 (LATS1), 9p21 (CDKN2A) was found infrequently.…”

“…The current reference treatment is maximum surgical resection, followed by radiotherapy [1,6]. For supratentorial tumors that infiltrate the adjacent brain, total or enlarged resection with the least possible tumor residue is recommended; with those of posterior fossa the complete resection is limited by the adjacent structures [1].…”

“…Chemotherapy is offered as an alternative in very young children to defer radiotherapy and avoid side effects in cognitive, endocrine areas [1,[6][7][8]. The results obtained with chemotherapy are regular, agents such as cisplatin are the most used with responses referred up to 30%.…”

“…Ependymomas are central nervous system (CNS) neoplasms classified according to the World Health Organization (WHO) in grades I to III (benign to undifferentiated with anaplastic changes), according to statistics, they make up approximately 10% among neoplasms of the CNS and increased up to 30% in the population below 3 years [1], in childhood is the third most frequent tumor after the pilocytic astrocytoma and medulloblastoma [2]. The origin is postulated in the cells of the radial glia [2].…”