Universität zu Köln

Juenger, Stephanie T., Mynarek, Martin, Wohlers, Inken, Doerner, Evelyn, zur Muehlen, Anja, Velez-Char, Natalia, von Hoff, Katja, Rutkowski, Stefan, Warmuth-Metz, Monika, Kortmann, Rolf-Dieter, Timmermann, Beate, Rahmann, Sven, Klein-Hitpass, Ludger, von Bueren, Andre O. and Pietsch, Torsten (2019). 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 Neuropathol. Commun., 7 (1). LONDON: BMC. ISSN 2051-5960

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Abstract

IntroductionRisk 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.MethodsTumor samples of 134 patients aged 0.2-15.9years 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.ResultsResidual 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.ConclusionThe 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Juenger, Stephanie T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mynarek, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohlers, Inken UNSPECIFIED UNSPECIFIED UNSPECIFIED Doerner, Evelyn UNSPECIFIED UNSPECIFIED UNSPECIFIED zur Muehlen, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Velez-Char, Natalia UNSPECIFIED UNSPECIFIED UNSPECIFIED von Hoff, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Rutkowski, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Warmuth-Metz, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Kortmann, Rolf-Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Timmermann, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahmann, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein-Hitpass, Ludger UNSPECIFIED UNSPECIFIED UNSPECIFIED von Bueren, Andre O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pietsch, Torsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-127608
DOI:	10.1186/s40478-019-0820-5
Journal or Publication Title:	Acta Neuropathol. Commun.
Volume:	7
Number:	1
Date:	2019
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	2051-5960
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PEDIATRIC INTRACRANIAL EPENDYMOMAS; SET ENRICHMENT ANALYSIS; EXPRESSION; CHILDREN; CANCER Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12760