[en] The mainstay of treatment 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 part of the standard of care, however, the predictive significance of most of these targets in central nervous system (CNS) tumors remains less well-studied. Despite that, there is increasing use of advanced molecular diagnostics that identify potential targets, and tumor-agnostic regulatory approvals on targets also present in CNS tumors have been granted. This raises the question of when and for which targets it is meaningful to test in adult patients with CNS tumors. This evidence-based guideline 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, and TSC1/2) and altered genomic stability (mismatch repair, POLE, high tumor mutational burden (TMB), homologous recombination deficiency) in adult patients with gliomas, glioneuronal and neuronal tumors. At present, targeted treatment for BRAF p.V600E alterations is to be considered part of the standard of care for patients with recurrent gliomas, pending regulatory approval. For approved tumor agnostic treatments for NTRK fusions and high TMB, the evidence for efficacy in adult patients with CNS tumors is very limited, and treatment should preferably be given within prospective clinical registries and trials. For targeted treatment of CNS tumors with FGFR fusions or mutations, clinical trials are ongoing to confirm modest activity so far observed in basket trials. For all other reviewed targets, evidence of benefit in CNS tumors is currently lacking, and testing/treatment should be in the context of available clinical trials.
Disciplines :
Oncology
Author, co-author :
Capper, David ; Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. ; German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Reifenberger, Guido; Institute of Neuropathology and German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Heinrich Heine University, Medical Faculty University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
French, Pim J; Department of Neurology, Brain Tumor Center at Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.
Schweizer, Leonille ; Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. ; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, German Cancer Research Center (DKFZ), Heidelberg, Germany. ; Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany.
Weller, Michael ; Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Touat, Mehdi; Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.
NICLOU, Simone P. ; Department of Cancer Research, NORLUX Neuro-Oncology Laboratory, Luxembourg Institute of Health, 6A, rue Nicolas Ernest-Barblé, L-1210 Luxembourg.
Euskirchen, Philipp ; Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. ; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Klinik für Neurologie, Charitéplatz 1, 10117 Berlin, Germany. ; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité Comprehensive Cancer Center, Charitéplatz 1, 10117 Berlin, Germany.
Haberler, Christine ; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.
Hegi, Monika E; Neuroscience Research Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Brandner, Sebastian ; Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London London, UK. ; Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK.
Le Rhun, Emilie; Department of Neurosurgery and Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Rudà, Roberta; Division of Neurology, Castelfranco Veneto/Treviso Hospital. ; Division of Neuro-Oncology, Department of Neuroscience, University of Turin, Turin, Italy.
Sanson, Marc; Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.
Tabatabai, Ghazaleh ; Department of Neurology & Interdisciplinary Neuro-Oncology, University Hospital Tübingen and Hertie Institute for Clinical Brain Research, Eberhard Karls University Tübingen. ; Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen. ; German Cancer Consortium (DKTK), partner site Tübingen, Eberhard Karls University Tübingen.
Sahm, Felix ; Department of Neuropathology, University Hospital Heidelberg, CCU Neuropathology, Heidelberg, Germany. ; German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Wen, Patrick Y; Center For Neuro-Oncology, Dana-Farber Cancer institute and Harvard Medical School, Boston, USA.
Wesseling, Pieter; Department of Pathology, Amsterdam University Medical Centers/VUmc (De Boelelaan 1117, 1081 HV) Amsterdam, The Netherlands. ; Laboratory for Childhood Cancer Pathology, Princess Máxima Center for Pediatric Oncology (Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.
Preusser, Matthias ; Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
van den Bent, Martin J ; Department of Neurology, Brain Tumor Center at Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.
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