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

in Acta neuropathologica by Catherine Godfraind, Joanna M Kaczmarska, Mehmet Kocak, James Dalton, Karen D Wright, Robert A Sanford, Fredrick A Boop, Amar Gajjar, Thomas E Merchant, David W Ellison

TLDR

  • This study looked at children with a type of brain tumor called ependymoma. They wanted to figure out a way to group these children based on their tumor's features so that doctors could give them the best treatment. They looked at things like how much of the tumor was removed during surgery, how many cells the tumor had, and how much of a certain gene was present in the tumor. They found that some of these features were more important than others in predicting how well the children would do after treatment. They also found that some children with a certain type of ependymoma were at higher risk for bad side effects from treatment, while others were at lower risk. This information could help doctors make better decisions about how to treat these children in the future.

Abstract

No reliable classification is in clinical use 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 has examined associations between clinicopathologic and cytogenetic variables and outcome in a trial cohort of children with ependymoma, with the aim of defining a practical scheme for stratifying this heterogeneous tumor. 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 loci on chromosomes 1q (EXO1), 6q (LATS1) and 9, including 9p21 (CDKN2A). Data relating to these clinicopathological and cytogenetic variables were compared with survival data in order to model disease risk groups. Extent of surgical resection was a significant determinant of outcome in both supratentorial and infratentorial compartments. Tumor cell density and mitotic count were associated with outcome among children with posterior fossa ependymomas (n = 119). Among pathologic features, only brain invasion was associated with outcome in children with supratentorial ependymomas (n = 27). For posterior fossa tumors, gain of 1q was independently associated with outcome and in combination with clinicopathological variables defined both a two-tier and three-tier system of disease risk. 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 sub-total resection and brain invasion.

Overview

  • The study aims to define a practical scheme for stratifying ependymoma in children, a heterogeneous tumor with no reliable classification for therapeutic stratification. The study evaluates associations between clinicopathologic and cytogenetic variables and outcome in a trial cohort of children with ependymoma. The methodology used includes intracranial ependymomas from children treated on the RT1 trial at St. Jude Children's Research Hospital, with data relating to clinicopathological and cytogenetic variables compared with survival data to model disease risk groups. The primary objective is to define a two-tier and three-tier system of disease risk for posterior fossa ependymomas, and to identify risk factors for pediatric supratentorial tumors.

Comparative Analysis & Findings

  • The study found that extent of surgical resection was a significant determinant of outcome in both supratentorial and infratentorial compartments. Tumor cell density and mitotic count were associated with outcome among children with posterior fossa ependymomas. Brain invasion was associated with outcome in children with supratentorial ependymomas. Gain of 1q was independently associated with outcome and in combination with clinicopathological variables defined both a two-tier and three-tier system of disease risk for posterior fossa tumors. Risk factors for pediatric supratentorial tumors are limited to sub-total resection and brain invasion.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice, as they provide a practical scheme for stratifying ependymoma in children. The two-tier and three-tier system of disease risk defined for posterior fossa tumors can be used to identify patients at high risk for adverse therapeutic effects and those who may benefit from more aggressive treatment. The study also identifies risk factors for pediatric supratentorial tumors, which can inform future research and clinical decision-making. Limitations of the study include the small sample size and the need for further validation of the disease risk groups defined. Future research could explore the use of additional clinicopathological and cytogenetic variables to refine the disease risk model and improve its predictive accuracy.
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