Telomerase reverse transcriptase promoter mutation- and O6-methylguanine DNA methyltransferase promoter methylation-mediated sensitivity to temozolomide in isocitrate dehydrogenase-wild-type glioblastoma: is there a link?

AIM OF THE STUDY: Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wild-type glioblastoma is essentially limited to patients with O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TERT) promoter hotspot mutations may have an impact on the prognostic role of the MGMT status in patients with glioblastoma. METHODS: MGMT promoter methylation and TERT promoter mutation status were retrospectively assessed in a prospective cohort of patients with IDH-wild-type glioblastoma of the German Glioma Network (GGN) (n = 298) and an independent retrospective cohort from Düsseldorf, Germany, and Zurich, Switzerland (n = 302). RESULTS: In the GGN cohort, but not in the Düsseldorf/Zurich cohort, TERT promoter mutation was moderately associated with inferior outcomes in patients with MGMT promoter-unmethylated tumours (hazard ratio 1.74; 95% confidence interval: 1.07-2.82; p = 0.026). TERT promoter mutations were not associated with better outcomes in patients with MGMT promoter-methylated tumours in either cohort. The two different TERT promoter hotspot mutations (C228T and C250T) were not linked to distinct outcomes. CONCLUSIONS: Analysis of two independent cohorts of patients with glioblastoma did not confirm previous data, suggesting that TERT promoter mutations confer an enhanced benefit from TMZ in patients with MGMT promoter-methylated glioblastoma. Thus, diagnostic testing for TERT promoter mutations may not be required for prediction of TMZ sensitivity in patients with IDH-wild-type glioblastoma.

Cavernous brain malformations and their relation to black blood MRI in respect to vessel wall contrast enhancement.

BACKGROUND: Inflammatory responses are implicated as crucial patho-mechanisms of vascular brain malformations. Inflammation is suggested to be a key contributor to aneurysm rupture; however it is unclear whether inflammation contributes similarly to bleeding of cerebral cavernous malformations (CCMs). Black blood MRI is a sequence which identifies inflammation in blood vessel walls and in the present study is used to detect inflammatory response in CCMs. METHODS: Fifteen patients with 17 CCMs treated in our department in 2017 were retrospectively analysed. All patients received black blood MRIs and the results were analysed in correlation with, size and bleeding of CCMs. RESULTS: Size and bleeding status of CCMs did not correlate with contrast enhancement in the CCM wall. One of 3 patients with bleeding displayed contrast enhancement in black blood MRI, whereas the others had non enhancing lesions. Because of the small number of cases a statistical analysis was not performed. CONCLUSION: In this limited cohort, inflammatory reactions in CCMs could not be detected by black blood MRI suggesting that the level of inflammation is minimal in these lesions and those different patho-mechanisms play a more important role in the rupture of CCMs.