6 Radiogenomics of circumscribed versus diffuse grade 4 gliomas based on standard molecular markers

Abstract Introduction The two main types of adult grade 4 gliomas are IDH1-wildtype glioblastomas and IDH-mutant astrocytomas. Each have their own molecular hallmarks. We sought to determine if there are differences in molecular markers between radiologically circumscribed and diffuse grade 4 gliomas. Method We carried out a retrospective analysis of a single surgeon’s experience of adult patients undergoing surgery for grade 4 gliomas at our institution between January 2019 and July 2024. Results We identified 145 patients who met our criteria, 4 of whom did not have information relating to molecular markers. Of the remaining 141 patients, 102 had radiologically circumscribed tumours while the rest had diffuse tumours. The two groups were comparable in terms of demographic characteristics. Extent of resection was greater in the circumscribed group compared to the diffuse group (39.6% gross total resections versus 17.9% (p = 0.0240)). The frequency of post-operative neurological deficits was higher in the circumscribed group (35.3% versus 18.0% (p = 0.0454)). Post-operative oncological management was similar in both groups and survival rates were also comparable. A greater proportion of diffuse tumours 15.4%) exhibited IDH1 mutations than circumscribed ones (4.0%) (p = 0.0283). There was no difference between the two cohorts in the frequency of loss of expression of ATRX, BRAF mutation rate, H3F3A mutation rate, the frequency of loss of heterozygosity at the 1p or 19q loci, eGFR amplification rate, the frequency of TERT promoter mutation, MGMT promoter methylation status, or the frequency of CDKN2A/B deletion. Conclusions A greater proportion of diffuse tumours exhibited IDH1 mutations than circumscribed ones. There were no other differences between the two groups in terms of molecular markers. This likely reflects a higher incidence of grade 4 astrocytomas in our diffuse tumour cohort.