A multi-institutional retrospective pooled outcome analysis of molecularly annotated pediatric supratentorial ZFTA- fused ependymoma

Chia Huan Ng; Denise Obrecht; Olivia Wells; Michal Zapotocky; David Sumerauer; Hallie Coltin; Dong-Anh Khuong-Quang; David D Eisenstat; Kathryn M Kinross; Christine L White; Elizabeth M Algar; Amanda Luck; Hendrik Witt; Ulrich Schüller; Martin Mynarek; Torsten Pietsch; Nicolas U Gerber; Martin Benesch; Monika Warmuth-Metz; Rolf Kortmann; Brigitte Bison; Michael D Taylor; Stefan Rutkowski; Stefan M Pfister; David Tw Jones; Nicholas G Gottardo; Katja von Hoff; Kristian W Pajtler; Vijay Ramaswamy; Jordan R Hansford

doi:10.1093/noajnl/vdad057

A multi-institutional retrospective pooled outcome analysis of molecularly annotated pediatric supratentorial ZFTA- fused ependymoma

Neurooncol Adv. 2023 May 12;5(1):vdad057. doi: 10.1093/noajnl/vdad057. eCollection 2023 Jan-Dec.

Authors

Chia Huan Ng¹, Denise Obrecht², Olivia Wells¹, Michal Zapotocky³, David Sumerauer^{2

3}, Hallie Coltin^{4

5

6}, Dong-Anh Khuong-Quang¹, David D Eisenstat^{1

7

8}, Kathryn M Kinross^{7

9}, Christine L White^{7

8

10}, Elizabeth M Algar^{7

8}, Amanda Luck¹¹, Hendrik Witt¹², Ulrich Schüller², Martin Mynarek², Torsten Pietsch¹³, Nicolas U Gerber¹⁴, Martin Benesch¹⁵, Monika Warmuth-Metz¹⁶, Rolf Kortmann¹⁶, Brigitte Bison¹⁷, Michael D Taylor⁴, Stefan Rutkowski², Stefan M Pfister^{18

19}, David Tw Jones²⁰, Nicholas G Gottardo^{7

21}, Katja von Hoff²², Kristian W Pajtler¹⁸, Vijay Ramaswamy^{4

5

23}, Jordan R Hansford^{1

7

24}

Affiliations

¹ Children's Cancer Centre, Royal Children's Hospital, Murdoch Children's Research Institute, University of Melbourne, Melbourne, Australia.
² University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³ Department of Paediatric Haematology and Oncology, Charles University, 2nd Faculty of Medicine and Faculty Hospital Motol, Prague.
⁴ Developmental and Stem Cell Biology, Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Canada.
⁵ Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.
⁶ Division of Pediatric Hematology-Oncology, Charles-Bruneau Cancer Centre, CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.
⁷ Hudson Institute of Medical Research, Melbourne, Australia.
⁸ Department of Molecular and Translational Science, Monash University, Melbourne, Australia.
⁹ Australia and New Zealand Children's Haematology/Oncology Group, Melbourne, Australia.
¹⁰ Victorian Clinical Genetics Services, Melbourne, Australia.
¹¹ Michael Rice Cancer Centre, Women's and Children's Hospital; South Australian Health and Medical Research Institute, Adelaide, Australia.
¹² German Cancer Research Centre, DKFZ, Heidelberg, Germany.
¹³ Department of Neuropathology and DGNN Brain Tumor Reference Center, University Bonn Medical Centre, Germany.
¹⁴ Children's Hospital of Zurich, Switzerland.
¹⁵ Medical University of Graz, Austria.
¹⁶ University Hospital Leipzig, Leipzig, Germany.
¹⁷ University of Wuerzburg, Würzburg.
¹⁸ Hopp Children's Cancer Center Heidelberg (KiTZ) and Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁹ Department of Pediatric Oncology, Hematology, and Immunology, University Hospital Heidelberg, Heidelberg, Germany.
²⁰ Hopp Children's Cancer Center Heidelberg (KiTZ), Pediatric Glioma Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²¹ Perth Children's Hospital, Telethon Kid's Institute, Western Australia, Perth, Australia.
²² Charité Universitätsmedizin Berlin, Germany.
²³ Departments of Medical Biophysics and Pediatrics, University of Toronto, Toronto, ON, Canada.
²⁴ Michael Rice Cancer Centre, Women's and Children's Hospital; South Australia Health and Medical Research Institute; South Australia ImmunoGENomics Cancer Institute, University of Adelaide, Adelaide SA, Australia.

Abstract

Background: ZFTA-RELA (formerly known as c11orf-RELA) fused supratentorial ependymoma (ZFTAfus ST-EPN) has been recognized as a novel entity in the 2016 WHO classification of CNS tumors and further defined in the recent 2021 edition. ZFTAfus ST-EPN was reported to portend poorer prognosis when compared to its counterpart, YAP1 ST-EPN in some previously published series. The aim of this study was to determine the treatment outcome of molecularly confirmed and conventionally treated ZFTAfus ST-EPN patients treated in multiple institutions.

Methods: We conducted a retrospective analysis of all pediatric patients with molecularly confirmed ZFTAfus ST-EPN patients treated in multiple institutions in 5 different countries (Australia, Canada, Germany, Switzerland, and Czechia). Survival outcomes were analyzed and correlated with clinical characteristics and treatment approaches.

Results: A total of 108 patients were collated from multiple institutions in 5 different countries across three continents. We found across the entire cohort that the 5- and 10-year PFS were 65% and 63%, respectively. The 5- and 10-year OS of this cohort of patients were 87% and 73%. The rates of gross total resection (GTR) were high with 84 out of 108 (77.8%) patients achieving GTR. The vast majority of patients also received post-operative radiotherapy, 98 out of 108 (90.7%). Chemotherapy did not appear to provide any survival benefit in our patient cohort.

Conclusion: This is the largest study to date of contemporaneously treated molecularly confirmed ZFTAfus ST-EPN patients which identified markedly improved survival outcomes compared to previously published series. This study also re-emphasizes the importance of maximal surgical resection in achieving optimal outcomes in pediatric patients with supratentorial ependymoma.

Keywords: ZFTA-RELA; central nervous system tumors; molecular; pediatric; supratentorial ependymoma.