Validation of Updated Diagnostic Criteria: IDH-Wildtype Diffuse Astrocytoma with Molecular Features of Glioblastoma

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A committee recently agreed on a panel of three molecular criteria, able to identify isocitrate dehydrogenase wildtype (IDHwt) diffuse astrocytic gliomas (DA) exhibiting a more aggressive clinical course with shorter survival, resembling glioblastoma WHO grade IV [1]. The criteria are epidermal growth factor receptor amplification, telomerase reverse transcriptase promoter mutation and combined whole chromosome 7 gain and whole chromosome 10 loss. Only one molecular criteria is required to diagnose: “Diffuse astrocytic glioma, IDH wildtype, with molecular features of glioblastoma, WHO grade IV”. The aim of this study was to validate the updated diagnostic criteria.

Materials and Methods
Patients diagnosed with DA from 2004-2018, at Aalborg University Hospital were included. Tumor samples from the time of diagnosis were examined for the molecular markers using Next Generation Sequencing, immunohistochemistry and fluorescence in situ hybridization. Crude and adjusted cox regression analyses, log-rank tests and Kaplan-Meier survival curves were used to compare survival.
44 patients were included. Median follow-up was 9.1 years and shortest 1.1 years. The median overall survival of patients with IDHwt DA with or without one of the molecular criteria was 10 and 16.5 months, respectively (p=0.17). Cox regression analysis of the molecular criteria in the subgroup of patients with IDHwt tumors yielded a HR of 3.9 (95% CI; 0.49-31.3) and the adjusted model yielded a HR of 14.6 (95% CI; 0.76-277). An adjusted model including patients with both IDHwt and IDH-mutant tumors gave a HR of 3.89 (95% CI; 1.33-11.4).
The molecular criteria predicted a significantly poorer survival independent of IDH-status. In patients with IDHwt tumors, the molecular criteria trended towards poorer survival. Due to the limited sample size, we could not definitely validate the proposed model. A larger multicenter study is ongoing.
Publikationsdato26 aug. 2021
StatusUdgivet - 26 aug. 2021
BegivenhedDanske Kræftforskningsdage 2021 - Odeon Konferencecenter, Odense, Danmark
Varighed: 26 aug. 202127 aug. 2021


KonferenceDanske Kræftforskningsdage 2021
LokationOdeon Konferencecenter


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