DEGRO practical guideline for central nervous system radiation necrosis part 2: treatment

Denise Bernhardt^{1

2}, Laila König^{3

4

5

6

7}, Anca-L Grosu^{8

9}, Stefan Rieken¹⁰, Sandro M Krieg¹¹, Wolfgang Wick^{12

13}, Benedikt Wiestler¹⁴, Friederike Schmidt-Graf¹⁵, Felix Sahm¹⁶, Jens Gempt¹¹, Bernhard Meyer¹¹, Bernd J Krause¹⁷, Cordula Petersen¹⁸, Rainer Fietkau^{19

20}, Michael Thomas^{21

22

23}, Frank Giordano²⁴, Andrea Wittig-Sauerwein²⁵, Jürgen Debus^{8

3

4

5

6

7}, Ghazaleh Tabatabai^{26

27

28

29}, Peter Hau³⁰, Joachim Steinbach³¹, Stephanie E Combs^{32

33

8}; Expert Panel of the German Society of Radiation Oncology (DEGRO)

Affiliations

¹ Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany. Denise.bernhardt@mri.tum.de.
² Partner Sites Munich, Deutsches Konsortium für Translationale Krebsforschung (DKTK), Freiburg and Heidelberg, Germany. Denise.bernhardt@mri.tum.de.
³ Klinik für Radioonkologie und Strahlentherapie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
⁴ Heidelberger Ionenstrahltherapie-Zentrum (HIT), Im Neuenheimer Feld 450, 69120, Heidelberg, Germany.
⁵ Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
⁶ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
⁷ National Center for Tumor diseases (NCT), 69120, Heidelberg, Germany.
⁸ Partner Sites Munich, Deutsches Konsortium für Translationale Krebsforschung (DKTK), Freiburg and Heidelberg, Germany.
⁹ Department of Radiation Oncology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Robert-Koch-Str. 3, 79106, Freiburg, Germany.
¹⁰ Clinic of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
¹¹ Department of Neurosurgery, Technical University Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany.
¹² Clinical Cooperation Unit Neurooncology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
¹³ Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University Hospital, 69120, Heidelberg, Germany.
¹⁴ Department of Neuroradiology, Technical University Munich, School of Medicine, Klinikum rechts der Isar, 81675, Munich, Germany.
¹⁵ Department of Neurology, Technical University Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany.
¹⁶ Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
¹⁷ Department of Nuclear Medicine, Rostock University Medical Centre, 18057, Rostock, Germany.
¹⁸ Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
¹⁹ Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 2306, Erlangen, Germany.
²⁰ Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg (CCC ER-EMN), 91054, Erlangen, Germany.
²¹ Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, 69120, Heidelberg, Germany.
²² Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC-H), 69120, Heidelberg, Germany.
²³ National Center for Tumor Diseases (NCT), Heidelberg, Germany, 69120.
²⁴ Department of Radiation Oncology, University Hospital Bonn, 53127, Bonn, Germany.
²⁵ Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Bachstraße 18, 07743, Jena, Germany.
²⁶ Department of Neurosurgery, University Hospital Tuebingen, Eberhard Karls University Tuebingen, 72076, Tuebingen, Germany.
²⁷ Center for Neuro-Oncology, Comprehensive Cancer Center Tuebingen Stuttgart, University Hospital Tuebingen, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany.
²⁸ Department of Neurology, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany.
²⁹ Department Interdisciplinary Neuro-Oncology, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany.
³⁰ Wilhelm Sander-NeuroOncology Unit and Department of Neurology, University Hospital Regensburg, 93053, Regensburg, Germany.
³¹ Dr Senckenberg Institute of Neurooncology, University Hospital, 60325, Frankfurt am Main, Germany.
³² Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.
³³ Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München (HMGU), Ingolstädter Landstraße Ingolstädter Landstraße 1, 85764, Oberschleißheim, Germany.

PMID: 36038670
PMCID: PMC9581806
DOI: 10.1007/s00066-022-01973-8

Review

DEGRO practical guideline for central nervous system radiation necrosis part 2: treatment

Denise Bernhardt et al. Strahlenther Onkol. 2022 Nov.

. 2022 Nov;198(11):971-980.

doi: 10.1007/s00066-022-01973-8. Epub 2022 Aug 29.

Authors

Affiliations

¹ Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany. Denise.bernhardt@mri.tum.de.
² Partner Sites Munich, Deutsches Konsortium für Translationale Krebsforschung (DKTK), Freiburg and Heidelberg, Germany. Denise.bernhardt@mri.tum.de.
³ Klinik für Radioonkologie und Strahlentherapie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
⁴ Heidelberger Ionenstrahltherapie-Zentrum (HIT), Im Neuenheimer Feld 450, 69120, Heidelberg, Germany.
⁵ Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
⁶ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
⁷ National Center for Tumor diseases (NCT), 69120, Heidelberg, Germany.
⁸ Partner Sites Munich, Deutsches Konsortium für Translationale Krebsforschung (DKTK), Freiburg and Heidelberg, Germany.
⁹ Department of Radiation Oncology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Robert-Koch-Str. 3, 79106, Freiburg, Germany.
¹⁰ Clinic of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
¹¹ Department of Neurosurgery, Technical University Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany.
¹² Clinical Cooperation Unit Neurooncology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
¹³ Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University Hospital, 69120, Heidelberg, Germany.
¹⁴ Department of Neuroradiology, Technical University Munich, School of Medicine, Klinikum rechts der Isar, 81675, Munich, Germany.
¹⁵ Department of Neurology, Technical University Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany.
¹⁶ Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
¹⁷ Department of Nuclear Medicine, Rostock University Medical Centre, 18057, Rostock, Germany.
¹⁸ Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
¹⁹ Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 2306, Erlangen, Germany.
²⁰ Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg (CCC ER-EMN), 91054, Erlangen, Germany.
²¹ Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, 69120, Heidelberg, Germany.
²² Member of the German Center for Lung Research (DZL), Translational Lung Research Center Heidelberg (TLRC-H), 69120, Heidelberg, Germany.
²³ National Center for Tumor Diseases (NCT), Heidelberg, Germany, 69120.
²⁴ Department of Radiation Oncology, University Hospital Bonn, 53127, Bonn, Germany.
²⁵ Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Bachstraße 18, 07743, Jena, Germany.
²⁶ Department of Neurosurgery, University Hospital Tuebingen, Eberhard Karls University Tuebingen, 72076, Tuebingen, Germany.
²⁷ Center for Neuro-Oncology, Comprehensive Cancer Center Tuebingen Stuttgart, University Hospital Tuebingen, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany.
²⁸ Department of Neurology, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany.
²⁹ Department Interdisciplinary Neuro-Oncology, Eberhard Karls University of Tuebingen, 72076, Tuebingen, Germany.
³⁰ Wilhelm Sander-NeuroOncology Unit and Department of Neurology, University Hospital Regensburg, 93053, Regensburg, Germany.
³¹ Dr Senckenberg Institute of Neurooncology, University Hospital, 60325, Frankfurt am Main, Germany.
³² Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany.
³³ Institute of Radiation Medicine (IRM), Department of Radiation Sciences (DRS), Helmholtz Zentrum München (HMGU), Ingolstädter Landstraße Ingolstädter Landstraße 1, 85764, Oberschleißheim, Germany.

PMID: 36038670
PMCID: PMC9581806
DOI: 10.1007/s00066-022-01973-8

Abstract

Purpose: The Working Group for Neurooncology of the German Society for Radiation Oncology (DEGRO; AG NRO) in cooperation with members of the Neurooncological Working Group of the German Cancer Society (DKG-NOA) aimed to define a practical guideline for the diagnosis and treatment of radiation-induced necrosis (RN) of the central nervous system (CNS).

Methods: Panel members of the DEGRO working group invited experts, participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for medical treatment of RN, including bevacizumab, in clinical routine.

Conclusion: Diagnosis and treatment of RN requires multidisciplinary structures of care and defined processes. Diagnosis has to be made on an interdisciplinary level with the joint knowledge of a neuroradiologist, radiation oncologist, neurosurgeon, neuropathologist, and neurooncologist. If the diagnosis of blood-brain barrier disruptions (BBD) or RN is likely, treatment should be initiated depending on the symptoms, location, and dynamic of the lesion. Multiple treatment options are available (such as observation, surgery, steroids, and bevacizumab) and the optimal approach should be discussed in an interdisciplinary setting. In this practice guideline, we offer detailed treatment strategies for various scenarios.

Keywords: Bevacizumab; Blood–brain barrier disruptions; Brain metastases; Glioma; Radiation necrosis; Stereotactic radiotherapy; Steroids.

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Conflict of interest statement

D. Bernhardt reports personal fees and honoraria from Accuray Inc., AstraZeneca, and Novocure GmbH outside the submitted work. DB’s spouse is employed at Gilead Science. L. König reports grants from Ruprecht-Karls Universität Heidelberg, and personal fees from Accuray Inc. and Novocure GmbH outside the submitted work. J. Debus: institution received research grants from Merck Serono, institution received consultation honoraria from Merck serono, JD received travel reimbursement from Merck Serono, institution received research grants from Siemens Healthineers and Accuray. S. Rieken is consultant for Brainlab AG (Munich, Germany) and Ulrich Medical (Ulm, Germany). S.K. received honoraria from Nexstim Plc (Helsinki, Finland), Spineart Deutschland GmbH (Frankfurt, Germany), Medtronic (Meerbusch, Germany), and Carl Zeiss Meditec (Oberkochen, Germany). M. Thomas reports personal fees, honoraria for advisory boards, and research funding from AstraZeneca, Beigene, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Daiichi Sankyo, GlaxoSmithKline, Janssen Oncology, Lilly, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, and Takeda. F. Giordano reports research grants, honoraria, and travel expenses from Carl Zeiss Meditec AG and NOXXON Pharma AG, personal fees from MVZ Venusberg GmbH, and consulting/speaker honoraria from Bristol Myers Squibb, Medac GmbH, Merck Sharp & Dohme, Elsevier, AstraZeneca, and Guerbet SA. A.-L. Grosu, S.M. Krieg, W. Wick, B. Wiestler, F. Schmidt-Graf, F. Sahm, J. Gempt, B. Meyer, B.J. Krause, C. Petersen, R. Fietkau, A. Wittig-Sauerwein, G. Tabatabai, P. Hau, J. Steinbach, S.E. Combs, and the Expert Panel of the German Society of Radiation Oncology (DEGRO) declare that they have no competing interests.

References

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DEGRO practical guideline for central nervous system radiation necrosis part 2: treatment

Affiliations

DEGRO practical guideline for central nervous system radiation necrosis part 2: treatment

Authors

Affiliations

Abstract

Conflict of interest statement

References

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