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

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.