Abstract
Abstract BACKGROUND The introduction of targeted therapies (TT) has provided few new options for glioblastoma patients (pts). Implementing genomic profiling as standard-of-care may aid in finding new treatments for glioblastoma pts. Here, we report the impact of genomic profiling in pts with WHO grade 4 CNS tumors at the Department of Oncology, Rigshospitalet, Denmark. METHODS Eligible pts were ≥18 years of age, with newly diagnosed glioblastoma; astrocytoma, IDH mutated grade IV or diffuse midline glioma between January 2016 and December 2022. Whole exome sequencing (WES), whole genome sequencing (WGS) or panel sequencing with Trusight Oncology (TSO500) along with SNP-array analyses and RNAseq was performed on DNA/RNA extracted from tumor tissue. Tumor tissue from patients enrolled before 2021 were analyzed by WES, and from January 2021 and forth, WGS was used for frozen tissue and TSO500 for paraffin-embedded tissue. Each genomic profile was presented at a weekly national molecular tumor board meeting for multidisciplinary evaluation, treatment recommendations and matching with clinical trials. RESULTS 387 pts had tissue samples available for analysis. Tissue from 202 patients (52%) were analyzed using WES, 174 (45%) using WGS, and 11 (3%) using TSO500. As of May 2023, of the 343 sequenced pts that have progressed after standard therapy, 14 patients (4%) have been treated with molecularly matched TTs. The actionable targets were TMB-high ( >10mut/MB) (n = 4), FGFR-mutations/-fusions (n = 4), BRAFv600E (n = 2), NTRK-fusions (n = 2), PDGFRA-fusion (n = 1) and MET-mutation (n = 1). Additionally, germline mutations were reported in 8 patients (2%). CONCLUSION Genomic profiling revealed actionable targets and new therapeutic options for glioblastoma pts. A full and updated overview of patient characteristics, actionable targets and survival data will be presented at the meeting.
Published Version
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