ESTRO 2023

Session Item

Sunday

May 14

15:15 - 16:15

Stolz 1

CNS

Co-Chair: Andrada Turcas, Romania;

Chair: Maximilian Niyazi, Germany

Session Type: Mini-Oral

Track: Clinical

Journey:

Adult intracranial ependymoma - the role of DNA methylation in radiotherapeutic treatment decisions

David Kaul, Germany

Presentation Number: MO-0552

Abstract

Abstract Title:

Adult intracranial ependymoma - the role of DNA methylation in radiotherapeutic treatment decisions

Authors:

David Kaul¹, Leonille Schweizer², Eilís Pérez², Simone Schmid², Carsten Dittmayer², Koichi Ichimura³, Ulrich Schüller⁴, Lasse Dührsen⁵, Michael Müther⁶, Werner Paulus⁷, Christian Thomas⁷, Marielena Gutt-Will⁸, Philippe Schucht⁸, Theoni Maragkou⁹, Jens Schittenhelm¹⁰, Franziska Eckert¹¹, Maximilian Niyazi¹², Daniel Fleischmann¹³, Mario Dorostkar¹⁴, Sven-Axel May¹⁵, Jan Walter¹⁶, Felix Ehret¹, Capper David², Malte Träger¹

¹Charité - Universitätsmedizin Berlin, Department of Radiation Oncology, Berlin, Germany; ²Charité - Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany; ³National Cancer Center Research Institute, Division of Brain Tumor Translational Research, Tokyo, Japan; ⁴University Medical Center Hamburg-Eppendorf, Institute of Neuropathology, Hamburg, Germany; ⁵University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Hamburg, Germany; ⁶University Hospital Münster, Department of Neurosurgery, Münster, Germany; ⁷University Hospital Münster, Institute of Neuropathology, Münster, Germany; ⁸Inselspital, Bern , Department of Neurosurgery, Bern, Switzerland; ⁹University of Bern, Institute of Pathology, Bern, Switzerland; ¹⁰University Hospital Tübingen, Institute of Pathology and Neuropathology, Tübingen, Germany; ¹¹University of Tübingen, Department of Radiation Oncology, Tübingen, Germany; ¹²Ludwig-Maximilians-University Munich, Department of Radiation Oncology, Munich, Germany; ¹³Ludwig-Maximilians-University Munich,, Department of Radiation Oncology, Munich, Germany; ¹⁴Ludwig-Maximilians-University Munich, Center for Neuropathology, Munich, Germany; ¹⁵Klinikum Chemnitz, Department of Neurosurgery, Chemnitz, Germany; ¹⁶Jena University Hospital, Department of Neurosurgery, Jena, Germany

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Purpose or Objective

A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas.

Material and Methods

Tumors diagnosed as intracranial ependymomas from 170 adult patients collected from eight diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were retrospectively correlated with progression-free survival (PFS).

Results

The classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6% and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (p=0.009) and postoperative radiotherapy (p=0.007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of prognosis within molecularly defined ependymoma classes.

Conclusion

DNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. Gross total resection and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.