Improved risk-stratification for posterior fossa ependymoma of childhood considering clinical, histological and genetic features – a retrospective analysis of the HIT ependymoma trial cohort | Acta Neuropathologica Communications | Full Text

Improved risk-stratification for posterior fossa ependymoma of childhood considering clinical, histological and genetic features – a retrospective analysis of the HIT ependymoma trial cohort | Acta Neuropathologica Communications | Full Text

Acta Neuropathologica Communications

Improved risk-stratification for posterior fossa ependymoma of childhood considering clinical, histological and genetic features – a retrospective analysis of the HIT ependymoma trial cohort

• Stephanie T. Jünger, 
• Martin Mynarek, 
• Inken Wohlers, 
• Evelyn Dörner, 
• Anja zur Mühlen, 
• Natalia Velez-Char, 
• Katja von Hoff, 
• Stefan Rutkowski, 
• Monika Warmuth-Metz, 
• Rolf-Dieter Kortmann, 
• Beate Timmermann, 
• Sven Rahmann, 
• Ludger Klein-Hitpass, 
• Andre O. von Bueren & 
• Torsten Pietsch 

Acta Neuropathologica Communications volume 7, Article number: 181 (2019) Cite this article

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Abstract

Introduction

Risk stratification of children with ependymomas of the posterior fossa in current therapeutic protocols is mainly based on clinical criteria. We aimed to identify independent outcome predictors for this disease entity by a systematic integrated analysis of clinical, histological and genetic information in a defined cohort of patients treated according to the German HIT protocols.

Methods

Tumor samples of 134 patients aged 0.2–15.9 years treated between 1999 and 2010 according to HIT protocols were analyzed for histological features including mitotic activity, necrosis and vascular proliferation and genomic alterations by SNP and molecular inversion probe analysis. Survival analysis was performed by Kaplan-Meier method with log rank test and multivariate Cox regression analysis.

Results

Residual tumor after surgery, chromosome 1q gain and structural genomic alterations were identified as predictors of significantly shorter event-free (EFS) and overall survival (OS). Furthermore, specific histological features including vascular proliferation, necrosis and high mitotic activity were predictive for shorter OS. Multivariate Cox regression revealed residual tumor, chromosome 1q gain and mitotic activity as independent predictors of both EFS and OS. Using these independent predictors of outcome, we were able to build a 3-tiered risk stratification model that separates patients with standard, intermediate and high risk, and which outperforms current stratification procedures.

Conclusion

The integration of defined clinical, histological and genetic parameters led to an improved risk-stratification model for posterior fossa ependymoma of childhood. After validation in independent cohorts this model may provide the basis for risk-adapted treatment of children with ependymomas of the posterior fossa.