Biom-39. genetic variants associated with distant recurrence in glioblastoma patients treated with standard therapy

Abstract Infiltrative growth is a hallmark of glioblastoma and is a major factor in therapeutic failure. Genetic variants predictive of distant recurrence may serve as novel treatment targets. The aim is to identify genetic variants associated with distance recurrence in glioblastoma patients. METHODS: From a prospective cohort of consecutive, non-selected glioblastoma patients administered standard therapy between 2016-2021 at Rigshospitalet, all patients with a genomic tumor profile were included. Distant recurrence was defined as a new contrast-enhancing tumor > 2 cm from the initial lesion. Tumor tissue was analyzed by RNA- and DNA-sequencing (WES or WGS). Genetic variants were defined as pathogenic and likely-pathogenic variants based on genomic reports. Predefined candidate biomarkers included: i) the most common genetic variants in the cohort (mutational frequency > 2%), ii) the number of reported variants per sample, and iii) groups of genetic variants according to the common signaling pathways. Candidates were screened for association with time to distant recurrence using univariate Cox regression analysis. Biomarkers with p < 0.20 were considered for multivariate analysis adjusted for known prognostic factors with death as the competing risk. RESULTS: A total of 236 patients were included, and 208 patients (88%) were evaluable for recurrence pattern. Distant recurrence was observed in 40 patients (19%). Patients with distant and local recurrence showed no difference in progression-free survival (p = 0.58), while distant recurrence tended to have a poor overall survival (OS, p = 0.09). The OS from time of first recurrence was significantly poorer for patients with distant recurrence compared to local recurrence (p = 0.01) with a median OS of 7.2 months (95%CI: 5.9-8.5) and 10.9 months (95%CI: 9.8-12). The median frequency of called gene variants was 4 (range 0-11) per sample. CONCLUSION: Patients with distant recurrence have a poor prognosis. Final analyses will be presented.