Newly Diagnosed Metastatic Intracranial Ependymoma in Children: Frequency, Molecular Characteristics, Treatment, and Outcome in the Prospective HIT Series

The oncologist

article

Martin Benesch¹  Ulrich Schüller²  Klaus Pietschmann⁵  Björn-Ole Juhnke²  Stephan Tippelt⁶  Gudrun Fleischhack⁶  Irene Schmid⁷  Christof M. Kramm⁸  Peter Vorwerk⁹  Andreas Beilken^1,10  Carl Friedrich Classen⁶  Martin Mynarek²  Pablo Hernáiz Driever^1,11  Gabriele Kropshofer^1,12  Thomas Imschweiler^1,13  Andreas Lemmer^1,14  Rolf-Dieter Kortmann⁵  Stefan Rutkowski²  Katja von Hoff²  Hendrik Witt^1,15  Monika Warmuth-Metz^1,18  Torsten Pietsch^1,19  Brigitte Bison^1,18  Stefan M. Pfister^1,15  Kristian W. Pajtler^1,15  Marcel Kool^1,15 

[1]Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz

[2]Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf

[3]Institute of Neuropathology, University Medical Center Hamburg-Eppendorf

[4]Research Institute Children's Cancer Center

[5]Department of Radiation Oncology, University of Leipzig

[6]University Children's Hospital of Essen

[7]Dr. von Hauner Children's Hospital, Ludwig Maximilians University

[8]Division of Pediatric Hematology and Oncology, University Medical Center Göttingen

[9]Department of Pediatric Hematology/Oncology, University Otto von Guericke Magdeburg

[10]Department of Pediatric Hematology/Oncology, Medical School Hannover

[11]Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health)

[12]Department of Pediatrics I, Medical University of Innsbruck

[13]Zentrum für Kinder- und Jugendmedizin

[14]Pediatric Hematology and Oncology Unit, Department of Pediatrics

[15]Hopp Children's Cancer Center (KiTZ), Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

[16]Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)

[17]Department of Pediatric Oncology, Heidelberg University Hospital

[18]Institute of Diagnostic and Interventional Neuroradiology, University Hospital Würzburg

[19]Institute of Neuropathology, Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy (DGNN), University of Bonn

关键词: Intracranial ependymoma;    Children;    Metastases;    Therapy;    Molecular subgroups;   

DOI  :  10.1634/theoncologist.2018-0489

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Data on frequency, clinical presentation, and outcome of primary metastatic intracranial ependymoma in children are scarce. Patients and Methods Prospective data on patients younger than 21 years with metastatic intracranial ependymoma at first diagnosis, registered from 2001 to 2014 in the HIT-2000 trial and the HIT-2000 Interim Registry, were analyzed. Results Of 453 registered patients with intracranial ependymoma and central neuropathology review, initial staging included spinal magnetic resonance imaging in all patients and lumbar cerebrospinal fluid (CSF) analysis in 402 patients. Ten patients (2.2%) had metastatic disease, including three with microscopic CSF positivity only (M1 metastasis stage, 0.7% of patients with CSF staging). Location of the primary tumor was supratentorial in four patients (all supratentorial RELA -fused ependymoma [ST-EPN-RELA]) and within the posterior fossa in five patients (posterior fossa ependymoma type A [PF-EPN-A], n  = 4; posterior fossa ependymoma not further classifiable, n  = 1), and multifocal in one patient. All four patients with ST-EPN-RELA were alive in first or second complete remission (CR) 7.5–12.3 years after diagnosis. All four patients with macroscopic metastases of posterior fossa or multifocal ependymoma died. Three patients with initial M1 stage (ST-EPN-RELA, n  = 1; PF-EPN-A, n  = 2) received chemotherapy and local irradiation and were alive in second or third CR 3.0–9.7 years after diagnosis. Progression-free and overall survival of the entire cohort at 5 years was 13% (±6%), and 58% (±16%), respectively. Conclusion Primary metastatic disease is rare in children with intracranial ependymoma. Prognosis may depend on molecular subgroup and extent of dissemination, and relevance of CSF analysis for initial staging remains to be clarified. Implications for Practice Childhood ependymoma presenting with metastasis at first diagnosis is very rare with a frequency of 2.4% in this population-based, well-characterized cohort. Detection of microscopic metastases in the cerebrospinal fluid was extremely rare, and impact on prognosis and respective treatment decision on irradiation field remains unclear. Initial metastatic presentation occurs in both supratentorial RELA -fused ependymoma and posterior fossa ependymoma. Prognosis may differ according to extent of metastasis and biological subgroup, with poor prognosis in diffusely spread metastatic posterior fossa ependymoma even after combination therapy with both intensive chemotherapy and craniospinal irradiation, which may help to guide individual therapeutic decisions for future patients.

【 授权许可】

CC BY|CC BY-NC