Comprehensive genetic profiling and molecularly guided treatment for patients with primary CNS tumors
Julia C. Kuehn, Patrick Metzger, Nicolas Neidert, Uta Matysiak, Linda Gräßel, Ulrike Philipp, Sabine Bleul, Thomas Pauli, J Falkenstein, Henriette Bertemes, Stepan Riemer Cysar, Maria Elena Hess, Anna Verena Frey, Jesús Duque‐Afonso, Elisabeth Schorb, Márcia Regina Machein, Jürgen Beck, Oliver Schnell, Nikolas von Bubnoff, Anna Lena Illert, Christoph Peters, Tilman Brummer, Marco Prinz, Cornelius Miething, Heiko Becker, Silke Laßmann, Martin Werner, Melanie Börries, Justus Duyster, Dieter Henrik Heiland, Roman Sankowski, Florian Scherer
Abstract
Despite major advances in molecular profiling and classification of primary brain tumors, personalized treatment remains limited for most patients. Here, we explored the feasibility of individual molecular profiling and the efficacy of biomarker-guided therapy for adult patients with primary brain cancers in the real-world setting within the molecular tumor board Freiburg, Germany. We analyzed genetic profiles, personalized treatment recommendations, and clinical outcomes of 102 patients with 21 brain tumor types. Alterations in the cell cycle, BRAF, and mTOR pathways most frequently led to personalized treatment recommendations. Molecularly informed therapies were recommended in 71% and implemented in 32% of patients with completed molecular diagnostics. The disease control rate following targeted treatment was 50% and the overall response rate was 30%, with a progression-free survival 2/1 ratio of at least 1.3 in 31% of patients. This study highlights the efficacy of molecularly guided treatment and the need for biomarker-stratified trials in brain cancers.