Clinical outcome following surgical resection and radiotherapy in adult patients with pleomorphic xanthoastrocytoma as defined by DNA methylation profiling

Maximilian Deng; Felix Hinz; Semi Harrabi; Dominik Sturm; Martin Sill; Andrey Korshunov; Tanja Eichkorn; Juliane Hörner-Rieber; Klaus Herfarth; Christine Jungk; Andreas Unterberg; Stefan Pfister; Wolfgang Wick; Andreas von Deimling; David Jones; Jürgen Debus; Felix Sahm; Laila König

doi:10.1093/nop/npad004

Clinical outcome following surgical resection and radiotherapy in adult patients with pleomorphic xanthoastrocytoma as defined by DNA methylation profiling

Neurooncol Pract. 2023 Jan 18;10(3):307-314. doi: 10.1093/nop/npad004. eCollection 2023 Jun.

Authors

Maximilian Deng^{1

2

3

4}, Felix Hinz⁵, Semi Harrabi^{1

2

3

4}, Dominik Sturm^{6

7

8}, Martin Sill^{6

9}, Andrey Korshunov^{5

6}, Tanja Eichkorn^{1

2

3

4}, Juliane Hörner-Rieber^{1

2

3

4

10}, Klaus Herfarth^{1

2

3

4}, Christine Jungk¹¹, Andreas Unterberg¹¹, Stefan Pfister^{6

8

9}, Wolfgang Wick^{3

12

13}, Andreas von Deimling⁵, David Jones^{6

7}, Jürgen Debus^{1

2

3

4

10}, Felix Sahm^{5

6}, Laila König^{1

2

3

4}

Affiliations

¹ Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
² Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.
³ National Center for Tumor Diseases (NCT), Heidelberg, Germany.
⁴ Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
⁵ Department of Neuropathology, Heidelberg University Hospital and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶ Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
⁷ Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁸ Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany.
⁹ Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁰ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹¹ Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
¹² Clinical Cooperation Unit Neurooncology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹³ Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.

Abstract

Background: Molecular brain tumor classification using DNA methylation profiling has revealed that the methylation-class of pleomorphic xanthoastrocytoma (mcPXA) comprised a substantial portion of divergent initial diagnoses, which had been established based on histology alone. This study aimed to characterize the survival outcome in patients with mcPXAs-in light of the diverse selected treatment regimes.

Methods: A retrospective cohort of adult mcPXAs were analyzed in regard to their progression-free survival following surgical resection and postoperative radiotherapy. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities and molecular tumor characteristics were further analyzed.

Results: Divergent initial histological diagnoses were encountered in 40.7%. There was no significant difference in local progression-free (PFS) and overall survival (OS) following gross total or subtotal resection. Postoperative radiotherapy was completed in 81% (22/27) following surgical intervention. Local PFS was 54.4% (95% CI: 35.3-84.0%) and OS was 81.3% (95% CI: 63.8-100%) after 3 years following postoperative radiotherapy. Initial relapses post-radiotherapy were primarily located in the previous tumor location and/or the planning target volume (PTV) (12/13). All patients in our cohort demonstrated the prognostically favorable pTERT-wildtype mcPXA.

Conclusion: Our study demonstrated that adult patients with mcPXAs display a worse progression-free survival compared to the reported WHO grade 2 PXAs. Future matched-pair analyses are required with a non-irradiated cohort to elucidate the benefit of postoperative radiotherapy in adult patients with mcPXAs.

Keywords: DNA methylation profiling; Pleomorphic xanthoastrocytoma; glioma; molecular diagnostics; radiotherapy.

© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.