Integrated diagnosis of grade 3-4 gliomas using targeted next-generation sequencing and traditional diagnostic data, and its overall implications on patient management

Adult gliomas vary significantly in terms of their genetics, epigenetics, phenotypes as well as clinical outcomes1. Optimal tumor classification that leads to more precise diagnoses, and which influences therapy selection is hence critically important. Targeted next-generation sequencing (NGS) is a highly reliable and efficient novel tool for the identification of biomarkers for the diagnosis of CNS tumors2. In this study, we aimed to determine the implications of integrating NGS findings with the traditional diagnostic data on clinical diagnostics and patient management. All patients who were diagnosed with glioma at our institution between 2019-2020 and whose tumor biopsy materials were analyzed by both traditional histomorphological and immunohistochemical diagnostic techniques as well as NGS were included in our study. Patients' information was retrieved from the electronic medical record. Data analyzed included the histopathologic diagnosis, tumor grade, ki67, and the mutation status of TP53 and /or IDH, as well as other genes such as BRAF and HER2 for some patients. The overall concordance between NGS and the traditional diagnostic tools for IDH and TP53 mutations was also evaluated. Further, we derived the overall survival of patients using the Kaplan-Meier estimate. We identified 9 patients with grade 3-4 gliomas whose biopsy materials were analyzed by NGS as well as traditional diagnostic tools. Our patients were 33.3% females and had a median age of 43 years old at diagnosis. In terms of the identification of gene mutations by NGS in comparison to immunohistochemistry (IHC), it was found that the concordance for mutant identification was 77.8% (7/9) for IDH mutations and 55.6% (5/9) for TP53 mutations. NGS further led to a change in patient management in which evidence-based targeted therapy (dabrafenib plus trametinib) was used for one patient (11.1%) with BRAF V600E mutated astroblastoma. Integrating NGS with traditional diagnostic tools for the diagnosis of gliomas can have significant implications on patients. Such integrated diagnosis can lead to more precise diagnosis, enhanced identification of molecular markers, and offers the potential of using targeted therapies for patients.