Distinct relapse pattern across molecular ependymoma types

Denise Obrecht-Sturm; Melanie Schoof; Alicia Eckhardt; Martin Mynarek; Mark R Gilbert; Kenneth Aldape; Terri S Armstrong; Vijay Ramaswamy; Michael Bockmayr; Katja von Hoff; Gudrun Fleischhack; Jonas E Adolph; Stephan Tippelt; Stefan M Pfister; Kristian Pajtler; Dominik Sturm; Richard Drexler; Franz L Ricklefs; Natalia Stepien; Johannes Gojo; Torsten Pietsch; Monika Warmuth-Metz; Rolf Kortmann; Beate Timmermann; Christine Haberler; Stefan Rutkowski; Ulrich Schüller

doi:10.1093/neuonc/noae166

Distinct relapse pattern across molecular ependymoma types

Neuro Oncol. 2024 Aug 22:noae166. doi: 10.1093/neuonc/noae166. Online ahead of print.

Authors

Denise Obrecht-Sturm¹, Melanie Schoof², Alicia Eckhardt^{2

3}, Martin Mynarek^{1

4}, Mark R Gilbert⁵, Kenneth Aldape⁶, Terri S Armstrong⁵, Vijay Ramaswamy⁷, Michael Bockmayr^{1

8}, Katja von Hoff^{9

10}, Gudrun Fleischhack¹¹, Jonas E Adolph¹¹, Stephan Tippelt¹¹, Stefan M Pfister^{12

13}, Kristian Pajtler^{12

13}, Dominik Sturm^{12

13}, Richard Drexler¹⁴, Franz L Ricklefs¹⁵, Natalia Stepien¹⁶, Johannes Gojo¹⁶, Torsten Pietsch¹⁷, Monika Warmuth-Metz¹⁸, Rolf Kortmann¹⁹, Beate Timmermann¹⁹, Christine Haberler²⁰, Stefan Rutkowski¹, Ulrich Schüller^{2

3}

Affiliations

¹ Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
² Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.
³ Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴ Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁵ Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, United States.
⁶ Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, United States.
⁷ Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁸ Institute of Pathology, Charité University Medicine, Berlin, Germany.
⁹ Department of Pediatric Oncology and Hematology, Charité University Medicine, Berlin, Germany.
¹⁰ Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
¹¹ Pediatrics III, Center for Translational Neuro- and Behavioral Sciences (CTNBS), University Hospital of Essen, Essen, Germany.
¹² Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
¹³ Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
¹⁴ Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
¹⁵ Department for Neurosurgery, University Medical Center Hamburg-Eppendorf, Germany.
¹⁶ Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
¹⁷ Department of Neuropathology and DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Bonn, Germany.
¹⁸ Institute of Diagnostic and Interventional Neuroradiology, University Hospital Wuerzburg, Würzburg, Germany.
¹⁹ Department of Radiation Oncology, University of Leipzig, Leipzig, Germany.
²⁰ Department of Neurology, Division of Neuropathology and Neurochemistry, Medical University of Vienna.

PMID: 39171767
DOI: 10.1093/neuonc/noae166

Abstract

Background: Ependymoma (EPN) is not a uniform disease but represents different disease types with biological and clinical heterogeneity. However, the pattern of when and where different types of EPN relapse is not yet comprehensively described.

Methods: We assembled 269 relapsed intracranial EPN from pediatric (n=233) and adult (n=36) patients from European and Northern American cohorts and correlated DNA methylation patterns and copy-number alterations with clinical information.

Results: The cohort comprised the following molecular EPN types: PF-EPN-A (n=177), ST-EPN-ZFTA (n=45), PF-EPN-B (n=31), PF-EPN-SE (n=12), and ST-EPN-YAP (n=4). First relapses of PF-EPN-B (PF: posterior-fossa) and PF-EPN-SE (SE: subependymoma) occurred later than of PF-EPN-A, ST-EPN-YAP (ST: supratentorial), or ST-EPN-ZFTA (median time to relapse: 4.3 and 6.0 years vs. 1.9/1.0/2.4 years; p<0.01). Metastatic or combined recurrences in PF-EPN-B and -A more often involved the spinal cord than in ST-EPN-ZFTA (72.7% and 40.0 vs. 12.5%; p<0.01). No distant relapses were observed in ST-EPN-YAP (n=4) or PF-EPN-SE (n=12). Post-relapse survival (PRS) was poor for PF-EPN-A and ST-EPN-ZFTA (5-year PRS: 44.5±4.4/47.8±9.1%), whereas PF-EPN-B and PF-EPN-SE displayed a 5-year PRS of 89.5±7.1/90.0±9.5% (p=0.03). However, 10-year PRS for PF-EPN-B dropped to 45.8±17.3%. Neither between radiation field and relapse pattern nor between radiation field and spinal involvement at relapse an impact was identified. Notably, all patients with relapsed ST-EPN-YAP did not receive upfront radiotherapy, but were successfully salvaged using irradiation at relapse.

Conclusions: Relapse patterns of specific EPN types are different. Future clinical trials, treatment adaptions, duration of surveillance and diagnostics should be planned incorporating entity-specific relapse information.

Keywords: ependymoma; metastatic; recurrence; relapse.

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