Neuro-OncologyXX(XX),1-14,2023|https://doi.org/10.1093/neuonc/noad008|Advance Access date 12 January 2023EANO guideline on rational molecular testing ofgliomas,glioneuronal,and neuronal tumors in adults fortargeted therapy selectionwnloadedDavid Capper,Guido Reifenberger,Pim J.French,Leonille Schweizer,Michael WellerMehdi Touat,Simone P.Niclou,Philipp Euskirchen Christine Haberler,Monika E.Hegi,Sebastian Brandner,Emilie Le Rhun,Roberta Ruda,Marc Sanson,Ghazaleh Tabatabai,Felix Sahm,Patrick Y.Wen,Pieter Wesseling,Matthias Preusser,and Martin J.van den BentAll author affiliations are listed atthe end of the article/acaCorresponding Author:M J van den Bent,MD,Department Neuro-Oncology,ErasmusMC Cancer Institute,DrMolenwaterplein 40,3015GD Rotterdam,The Netherlands(m.vandenbent@erasmusmc.nl).comAbstractThe mainstay of treatment for adult patients with gliomas,glioneuronal and neuronal tumors consists of combinations6of surgery,radiotherapy,and chemotherapy.For many systemic cancers,targeted treatments are a part of the standard3of care,however,the predictive significance of most of these targets in central nervous system(CNS)tumors remains9less well-studied.Despite that,there is increasing use of advanced molecular diagnostics that identify potential targets,and tumoragnostic regulatory approvals on targets also present in CNS tumors have been granted.This raises thequestion of when and for which targets it is meaningful to test in adult patients with CNS tumors.This evidence-basedguideline reviews the evidence available for targeted treatment for alterations in the RAS/MAPK pathway(BRAF NF1),in growth factor receptors(EGFR,ALK,fibroblast growth factor receptor(FGFR),neurotrophic tyrosine receptor kinase(NTRK),platelet-derived growth factor receptor alpha,and ROS1),in cell cycle signaling(CDK4/6,MDM2/4,andTSC1/2)and altered genomic stability(mismatch repair,POLE,high tumor mutational burden(TMB),homologous recombina-tion deficiency)in adult patients with gliomas,glioneuronal and neuronal tumors.At present,targeted treatment for883BRAF p.V600E alterations is to be considered part of the standard of care for patients with recurrent gliomas,pendingregulatory approval.For approved tumor agnostic treatments for NTRK fusions and high TMB,the evidence for efficacyin adult patients with CNS tumors is very limited,and treatment should preferably be given within prospective clinicalregistries and trials.For targeted treatment of CNS tumors with FGFR fusions or mutations,clinical trials are ongoingto confimm modest activity so far observed in basket trials.For all other reviewed targets,evidence of benefit in CNStumors is currently lacking,and testing/treatment should be in the context of available clinical trials.Key PointsPanel diagnostics are a more efficient way to identify rare genetic variants than target-specific assays.At present,only the clinical benefit in patients with BRAF p.V600E mutant recurrent CNStumors is sufficiently well established to consid
