European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection

Felix Sahm; Luca Bertero; Sebastian Brandner; David Capper; Roland Goldbrunner; Michael D Jenkinson; Michel Kalamarides; Katrin Lamszus; Nathalie L Albert; Maximilian J Mair; Anna S Berghoff; Christian Mawrin; Hans-Georg Wirsching; Sybren Ln Maas; David R Raleigh; Guido Reifenberger; Leonille Schweizer; Abigail K Suwala; Ghazaleh Tabatabai; Emeline Tabouret; Susan Short; Patrick Y Wen; Michael Weller; Emilie Le Rhun; Pieter Wesseling; Martin van den Bent; Matthias Preusser

doi:10.1093/neuonc/noae253

European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection

Felix Sahm, Luca Bertero, Sebastian Brandner, David Capper, Roland Goldbrunner, Michael D Jenkinson, Michel Kalamarides, Katrin Lamszus, Nathalie L Albert, Maximilian J Mair, Anna S Berghoff, Christian Mawrin, Hans-Georg Wirsching, Sybren Ln Maas, David R Raleigh, Guido Reifenberger, Leonille Schweizer, Abigail K Suwala, Ghazaleh Tabatabai, Emeline TabouretSusan Short, Patrick Y Wen, Michael Weller, Emilie Le Rhun, Pieter Wesseling, Martin van den Bent, Matthias Preusser

Pathology

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Abstract

Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to a lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy, or radioligand therapy. Here, we review the evidence for a predictive role of a wide range of molecular alterations and markers including NF2, AKT1, SMO, SMARCE1, PIK3CA, CDKN2A/B, CDK4/6, TERT, TRAF7, BAP1, KLF4, ARID1/2, SUFU, PD-L1, SSTR2A, PR/ER, mTOR, VEGF(R), PDGFR, as well as homologous recombination deficiency, genomic copy number variations, DNA methylation classes, and combined gene expression profiles. In our assessment based on the established ESMO ESCAT (European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets) evidence-level criteria, no molecular target reached ESCAT I ("ready for clinical use") classification, and only mTOR pathway activation and NF2 alterations reached ESCAT II ("investigational") classification, respectively. Our evaluations may guide targeted therapy selection in clinical practice and clinical trial efforts and highlight areas for which additional research is warranted.

Original language	English
Article number	noae253
Pages (from-to)	869-883
Number of pages	15
Journal	Neuro-Oncology
Volume	27
Issue number	4
Early online date	23 Nov 2024
DOIs	https://doi.org/10.1093/neuonc/noae253
Publication status	Published - 1 Apr 2025

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

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Sahm, F., Bertero, L., Brandner, S., Capper, D., Goldbrunner, R., Jenkinson, M. D., Kalamarides, M., Lamszus, K., Albert, N. L., Mair, M. J., Berghoff, A. S., Mawrin, C., Wirsching, H.-G., Maas, S. L., Raleigh, D. R., Reifenberger, G., Schweizer, L., Suwala, A. K., Tabatabai, G., ... Preusser, M. (2025). European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection. Neuro-Oncology, 27(4), 869-883. Article noae253. https://doi.org/10.1093/neuonc/noae253

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title = "European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection",

abstract = "Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to a lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy, or radioligand therapy. Here, we review the evidence for a predictive role of a wide range of molecular alterations and markers including NF2, AKT1, SMO, SMARCE1, PIK3CA, CDKN2A/B, CDK4/6, TERT, TRAF7, BAP1, KLF4, ARID1/2, SUFU, PD-L1, SSTR2A, PR/ER, mTOR, VEGF(R), PDGFR, as well as homologous recombination deficiency, genomic copy number variations, DNA methylation classes, and combined gene expression profiles. In our assessment based on the established ESMO ESCAT (European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets) evidence-level criteria, no molecular target reached ESCAT I ({"}ready for clinical use{"}) classification, and only mTOR pathway activation and NF2 alterations reached ESCAT II ({"}investigational{"}) classification, respectively. Our evaluations may guide targeted therapy selection in clinical practice and clinical trial efforts and highlight areas for which additional research is warranted.",

author = "Felix Sahm and Luca Bertero and Sebastian Brandner and David Capper and Roland Goldbrunner and Jenkinson, {Michael D} and Michel Kalamarides and Katrin Lamszus and Albert, {Nathalie L} and Mair, {Maximilian J} and Berghoff, {Anna S} and Christian Mawrin and Hans-Georg Wirsching and Maas, {Sybren Ln} and Raleigh, {David R} and Guido Reifenberger and Leonille Schweizer and Suwala, {Abigail K} and Ghazaleh Tabatabai and Emeline Tabouret and Susan Short and Wen, {Patrick Y} and Michael Weller and {Le Rhun}, Emilie and Pieter Wesseling and {van den Bent}, Martin and Matthias Preusser",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Published by Oxford University Press on behalf of the Society for Neuro-Oncology.",

year = "2025",

month = apr,

day = "1",

doi = "10.1093/neuonc/noae253",

language = "English",

volume = "27",

pages = "869--883",

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Sahm, F, Bertero, L, Brandner, S, Capper, D, Goldbrunner, R, Jenkinson, MD, Kalamarides, M, Lamszus, K, Albert, NL, Mair, MJ, Berghoff, AS, Mawrin, C, Wirsching, H-G, Maas, SL, Raleigh, DR, Reifenberger, G, Schweizer, L, Suwala, AK, Tabatabai, G, Tabouret, E, Short, S, Wen, PY, Weller, M, Le Rhun, E, Wesseling, P, van den Bent, M & Preusser, M 2025, 'European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection', Neuro-Oncology, vol. 27, no. 4, noae253, pp. 869-883. https://doi.org/10.1093/neuonc/noae253

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T1 - European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection

AU - Sahm, Felix

AU - Bertero, Luca

AU - Brandner, Sebastian

AU - Capper, David

AU - Goldbrunner, Roland

AU - Jenkinson, Michael D

AU - Kalamarides, Michel

AU - Lamszus, Katrin

AU - Albert, Nathalie L

AU - Mair, Maximilian J

AU - Berghoff, Anna S

AU - Mawrin, Christian

AU - Wirsching, Hans-Georg

AU - Maas, Sybren Ln

AU - Raleigh, David R

AU - Reifenberger, Guido

AU - Schweizer, Leonille

AU - Suwala, Abigail K

AU - Tabatabai, Ghazaleh

AU - Tabouret, Emeline

AU - Short, Susan

AU - Wen, Patrick Y

AU - Weller, Michael

AU - Le Rhun, Emilie

AU - Wesseling, Pieter

AU - van den Bent, Martin

AU - Preusser, Matthias

PY - 2025/4/1

Y1 - 2025/4/1

N2 - Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to a lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy, or radioligand therapy. Here, we review the evidence for a predictive role of a wide range of molecular alterations and markers including NF2, AKT1, SMO, SMARCE1, PIK3CA, CDKN2A/B, CDK4/6, TERT, TRAF7, BAP1, KLF4, ARID1/2, SUFU, PD-L1, SSTR2A, PR/ER, mTOR, VEGF(R), PDGFR, as well as homologous recombination deficiency, genomic copy number variations, DNA methylation classes, and combined gene expression profiles. In our assessment based on the established ESMO ESCAT (European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets) evidence-level criteria, no molecular target reached ESCAT I ("ready for clinical use") classification, and only mTOR pathway activation and NF2 alterations reached ESCAT II ("investigational") classification, respectively. Our evaluations may guide targeted therapy selection in clinical practice and clinical trial efforts and highlight areas for which additional research is warranted.

AB - Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to a lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy, or radioligand therapy. Here, we review the evidence for a predictive role of a wide range of molecular alterations and markers including NF2, AKT1, SMO, SMARCE1, PIK3CA, CDKN2A/B, CDK4/6, TERT, TRAF7, BAP1, KLF4, ARID1/2, SUFU, PD-L1, SSTR2A, PR/ER, mTOR, VEGF(R), PDGFR, as well as homologous recombination deficiency, genomic copy number variations, DNA methylation classes, and combined gene expression profiles. In our assessment based on the established ESMO ESCAT (European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets) evidence-level criteria, no molecular target reached ESCAT I ("ready for clinical use") classification, and only mTOR pathway activation and NF2 alterations reached ESCAT II ("investigational") classification, respectively. Our evaluations may guide targeted therapy selection in clinical practice and clinical trial efforts and highlight areas for which additional research is warranted.

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U2 - 10.1093/neuonc/noae253

DO - 10.1093/neuonc/noae253

M3 - Article

C2 - 39577862

SN - 1522-8517

VL - 27

SP - 869

EP - 883

JO - Neuro-Oncology

JF - Neuro-Oncology

IS - 4

M1 - noae253

ER -

European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection

Abstract

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