Optimizing the risk stratification of astrocytic tumors by applying the cIMPACT- NOW Update 3 signature: real-word single center experience

Abstract

Purpose. Implementation of a useful genetic diagnosis for the clinical management of patients with astrocytic tumors. Methods. We investigated 314 prospectively recruited diffuse astrocytic tumours by applying the cIMPACT-NOW Update 3 signature. Results. The cIMPACT-NOW Update 3 (cIMPACT 3+) markers, i.e. alterations of TERT promoter, EGFR, and/or chromosome 7 and 10, characterized 98.5% of IDH-wt cases. Interestingly, it was also found in 57.5% of IDH-mut cases. According to the genomic profile, four genetic subgroups could be distinguished: 1) IDH-wt/cIMPACT 3-negative (=4); 2) IDH-mut/cIMPACT 3-negative (n=14); 3) IDH-mut/cIMPACT 3+ (n=20); and 4) IDH-wt/cIMPACT 3+ (n=276). Multivariate analysis confirmed that IDH1/2 mutations confer a favorable prognosis (IDH-wt, HR 2.91 95%, CI 1.40-6.05), and validated the prognostic value of the cIMPACT 3+ signature. Conclusions. To accurately identify relevant prognostic categories, overcoming the limitations of histopathology and immunohistochemistry, molecular-cytogenetic analyses must be fully integrated into the diagnostic work-up of astrocytic tumors.