The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants

Kristian W Pajtler^{1

2

3}, Stephen C Mack^{4

5}, Vijay Ramaswamy^{6

7}, Christian A Smith⁶, Hendrik Witt^{1

2

3}, Amy Smith⁸, Jordan R Hansford⁹, Katja von Hoff¹⁰, Karen D Wright¹¹, Eugene Hwang¹², Didier Frappaz¹³, Yonehiro Kanemura¹⁴, Maura Massimino¹⁵, Cécile Faure-Conter¹³, Piergiorgio Modena¹⁶, Uri Tabori⁷, Katherine E Warren¹⁷, Eric C Holland¹⁸, Koichi Ichimura¹⁹, Felice Giangaspero²⁰, David Castel^{21

22}, Andreas von Deimling^{23

24}, Marcel Kool^{1

3}, Peter B Dirks⁶, Richard G Grundy²⁵, Nicholas K Foreman²⁶, Amar Gajjar¹¹, Andrey Korshunov^{23

24}, Jonathan Finlay²⁷, Richard J Gilbertson²⁸, David W Ellison²⁹, Kenneth D Aldape³⁰, Thomas E Merchant³¹, Eric Bouffet⁷, Stefan M Pfister^{32

33

34}, Michael D Taylor³⁵

Affiliations

¹ Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany.
³ German Cancer Consortium (DKTK), Heidelberg, Germany.
⁴ Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
⁵ Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
⁶ Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
⁷ Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.
⁸ Arnold Palmer Hospital, Orlando, FL, USA.
⁹ Royal Children's Hospital, Melbourne, VIC, Australia.
¹⁰ Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
¹² Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC, USA.
¹³ Pediatric Neuro-Oncology Centre Léon Bérard, Lyon, France.
¹⁴ Department of Neurosurgery and Institute for Clinical Research, Osaka National Hospital, Osaka, Japan.
¹⁵ Fondazione IRCCS-Istituto Nazionale dei Tumori, Milan, Italy.
¹⁶ Laboratory of Genetics, Pathology Unit, S. Anna General Hospital, Como, Italy.
¹⁷ National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
¹⁸ Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹⁹ Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
²⁰ Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy.
²¹ Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.
²² UMR8203 "Vectorologie and Thérapeutiques Anticancéreuses", CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.
²³ Department of Neuropathology, University of Heidelberg, Heidelberg, Germany.
²⁴ Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁵ Children's Brain Tumour Research Centre, The Medical School, University of Nottingham, Nottingham, UK.
²⁶ Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA.
²⁷ Nationwide Children's Hospital and the Ohio State University, Columbus, OH, USA.
²⁸ Li Ka Shing Centre, CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
²⁹ Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
³⁰ Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
³¹ Department of Radiological Sciences, St Jude Children's Research Hospital, Memphis, TN, USA.
³² Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. s.pfister@dkfz.de.
³³ Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany. s.pfister@dkfz.de.
³⁴ German Cancer Consortium (DKTK), Heidelberg, Germany. s.pfister@dkfz.de.
³⁵ Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada. mdtaylor@sickkids.ca.

PMID: 27858204
PMCID: PMC5209402
DOI: 10.1007/s00401-016-1643-0

The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants

Kristian W Pajtler et al. Acta Neuropathol. 2017 Jan.

. 2017 Jan;133(1):5-12.

doi: 10.1007/s00401-016-1643-0. Epub 2016 Nov 17.

Authors

Affiliations

¹ Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany.
³ German Cancer Consortium (DKTK), Heidelberg, Germany.
⁴ Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
⁵ Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
⁶ Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
⁷ Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.
⁸ Arnold Palmer Hospital, Orlando, FL, USA.
⁹ Royal Children's Hospital, Melbourne, VIC, Australia.
¹⁰ Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
¹² Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC, USA.
¹³ Pediatric Neuro-Oncology Centre Léon Bérard, Lyon, France.
¹⁴ Department of Neurosurgery and Institute for Clinical Research, Osaka National Hospital, Osaka, Japan.
¹⁵ Fondazione IRCCS-Istituto Nazionale dei Tumori, Milan, Italy.
¹⁶ Laboratory of Genetics, Pathology Unit, S. Anna General Hospital, Como, Italy.
¹⁷ National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
¹⁸ Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹⁹ Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
²⁰ Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy.
²¹ Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.
²² UMR8203 "Vectorologie and Thérapeutiques Anticancéreuses", CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.
²³ Department of Neuropathology, University of Heidelberg, Heidelberg, Germany.
²⁴ Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁵ Children's Brain Tumour Research Centre, The Medical School, University of Nottingham, Nottingham, UK.
²⁶ Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA.
²⁷ Nationwide Children's Hospital and the Ohio State University, Columbus, OH, USA.
²⁸ Li Ka Shing Centre, CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
²⁹ Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
³⁰ Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
³¹ Department of Radiological Sciences, St Jude Children's Research Hospital, Memphis, TN, USA.
³² Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. s.pfister@dkfz.de.
³³ Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany. s.pfister@dkfz.de.
³⁴ German Cancer Consortium (DKTK), Heidelberg, Germany. s.pfister@dkfz.de.
³⁵ Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada. mdtaylor@sickkids.ca.

PMID: 27858204
PMCID: PMC5209402
DOI: 10.1007/s00401-016-1643-0

Abstract

Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2) the integration of molecular-based stratification schemes in future clinical trials for patients with ependymoma and (3) current therapy in the context of molecular subgroups. Discussion at the meeting generated a series of consensus statements and recommendations from the attendees, which comment on the prognostic evaluation and treatment decisions of patients with intracranial ependymoma (WHO Grade II/III) based on the knowledge of its molecular subgroups. The major consensus among attendees was reached that treatment decisions for ependymoma (outside of clinical trials) should not be based on grading (II vs III). Supratentorial and posterior fossa ependymomas are distinct diseases, although the impact on therapy is still evolving. Molecular subgrouping should be part of all clinical trials henceforth.

Keywords: Ependymoma; Posterior fossa; RELA; Subgroups; Treatment; Trial; YAP1.

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Figures

**Fig. 1**
General and molecular subgroup specific consensus statements on the clinical management of intracranial ependymoma

See this image and copyright information in PMC

References

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The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants

Affiliations

The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants

Authors

Affiliations

Abstract

Figures

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical