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

Autor: André O. von Bueren, Martin Mynarek, Stefan Rutkowski, Ludger Klein-Hitpass, Inken Wohlers, Torsten Pietsch, Stephanie T Jünger, Sven Rahmann, Beate Timmermann, Natalia Velez-Char, Monika Warmuth-Metz, Katja von Hoff, Rolf-Dieter Kortmann, Evelyn Dörner, Anja zur Mühlen
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Ependymoma
Oncology
Male
medicine.medical_specialty
Multivariate statistics
Neurology
Adolescent
Medizin
Infratentorial Neoplasms
Molecular Inversion Probe
Infratentorial Neoplasms / pathology
Ependymoma / epidemiology
Risk Assessment
lcsh:RC346-429
Pathology and Forensic Medicine
Cohort Studies
Cellular and Molecular Neuroscience
Posterior fossa
Infratentorial Neoplasms / genetics
Internal medicine
Germany
Genetics
Medicine
Humans
Risk Assessment / standards
Child
Survival analysis
Risk stratification
Neuropathology
lcsh:Neurology. Diseases of the nervous system
Retrospective Studies
ddc:618
business.industry
Proportional hazards model
Research
Ependymoma / pathology
Germany / epidemiology
Infant
medicine.disease
Log-rank test
Child
Preschool
Cohort
Ependymoma / genetics
Female
Neurology (clinical)
Infratentorial Neoplasms / epidemiology
business
Follow-Up Studies
Zdroj: Acta Neuropathologica Communications, Vol 7, Iss 1, Pp 1-12 (2019)
Acta Neuropathologica Communications
Acta neuropathologica communications, Vol. 7, No 1 (2019) P. 181
ISSN: 2051-5960
DOI: 10.1186/s40478-019-0820-5
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje