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Review
. 2025 Feb 10;27(2):331-337.
doi: 10.1093/neuonc/noae213.

Updated EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection-Update 1

Martin J van den Bent  1 , Enrico Franceschi  2 , Mehdi Touat  3 , Pim J French  1 , Ahmed Idbaih  4 , Giuseppe Lombardi  5 , Roberta Rudà  6 , Leonille Schweizer  7   8   9 , David Capper  10   11 , Marc Sanson  3 , Pieter Wesseling  12   13 , Michael Weller  14 , Marica Eoli  15 , Elena Anghileri  16 , Franck Bielle  17 , Phillipp Euskirchen  10   11 , Marjolein Geurts  1 , Patrick Y Wen  18 , Matthias Preusser  19
Affiliations
Review

Updated EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection-Update 1

Martin J van den Bent et al. Neuro Oncol. .

Abstract

The standard of care for adult patients with gliomas, glioneuronal, and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a major part of the standard treatment; however, the predictive significance of most of the targets for treatment in systemic cancer is less well-established in central nervous system tumors. In 2023 the European Association for NeuroOncology (EANO) Guideline Committee presented evidence-based recommendations for rational testing of molecular targets for targeted treatments. From all targets reviewed, only testing for BRAF V600E mutations was of proven clinical benefit; despite regulatory approvals for tumor agnostic treatment of NTRK gene fusions and high tumor mutational burden (TMB) for patients with adult brain tumors, the evidence of clinical benefit for adult patients was still limited. This guideline has a modular structure, allowing regular updating of individual sections and adding new ones. The present version (Update 1) presents a review of the rationale of testing for PTEN, H3F3A, MTAP, RET and IDH, and presents an update of the text on TMB high and mismatch repair deficiency. It also presents an overview of the therapeutic yield of routine next-generation sequencing for mutations and fusion detection. The Supplemental File II accompanying this version contains an in-depth review of all targets, whereas, in the main manuscript, the final recommendations of the revised and new targets are presented. Updates will be made on a regular basis.

Keywords: (glio)neuronal tumors; EANO guideline; IDH; diffuse glioma; targeted treatment.

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Conflict of interest statement

M.J.v.d.B. has received honoraria for consultancy from Anheart Therapeutics, Boehringer Ingelheim, Fore Biotherapeutics, Genenta, Incyte, Mundipharm, Chimerix, Roche, and Servier and support for travel to meetings by Servier. E.F. has nothing to disclose; M.T. has received Consulting from Servier, Novocure, TherAguix, Ono, Resilience; Research Grants from Sanofi; PJF has nothing to disclose; A.I. reports travel funding from Carthera, Leo Pharma; research grants from Transgene, Sanofi, Air Liquide and Nutritheragene; Consulting from Novocure, Novartis, Polytone Laser, Leo Pharma, Boehringer Ingelheim; G.L. declares consulting or advisory role funding from AbbVie, Bayer, Novartis, Orbus Therapeutics, BrainFarm, Celgene, Cureteq, Health4U, Braun, Janssen, BioRegio STERN, Servier, and Novocure; and travel funding from Roche and Bayer; R.R. Consulting from Novocure, Servier, Genenta, CureVac; Grants from Bayer; L.S. has nothing to disclose; D.C. has receivedresearch grants from Novocure; co-funder of Heidelberg Epigostix GmbH; P.W. has nothing to disclose; M.S. has received consulting from Genenta, Servier, Novocure, Research Grants from Astra-Zeneca and BMS’; M.W. has received research grants from Novartis, Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Anheart, Bayer, Curevac, Medac, Neurosense, Novartis, Novocure, Orbus, Pfizer, Philogen, Roche and Servier; M.E. has received consulting fees from Alexion, travel grant from Genenta; E.A., F.B., P.E. have nothing to disclose; M.G. has received a research grant from Evgen Pharm; P.Y.W. has received research support from Astra Zeneca, Black Diamond, Bristol Meyers Squibb, Chimerix, Eli Lily, Erasca, Global Coalition For Adaptive Research, Kazia, MediciNova, Merck, Novartis, Quadriga, Servier, VBI Vaccines. Advisory Board/Consultant: Anheart, Astra Zeneca, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, Glaxo Smith Kline, Kintara, Merck, Mundipharma, Novartis, Novocure, Prelude Therapeutics, Sagimet, Sapience, Servier, Symbio, Tango, Telix, VBI Vaccines; M.P. has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Böhringer-Ingelheim, Telix, Medscape.

Figures

Figure 1.
Figure 1.
Overview of molecular targets found in gliomas, glioneuronal tumors, and neuronal tumors of adults and associated ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) score. Notes: Numbers are rough estimates based on literature and public databases, data on rare or new subtypes for which only a few samples have been characterized may evolve. Whenever feasible, results have been translated into tumor types as they are defined according to the WHO 2021 central nervous system tumor classification. This may be responsible for variations in biomarker prevalence compared to past studies. Definitions of variants may vary between different studies (eg, rare mutations outside known hotspots of which the somatic status is unknown and oncogenic potential has not been determined). Single cases or discordant reports regarding target prevalence are not included in the table.
See this image and copyright information in PMC

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