Related Experiment Video
Updated: Sep 17, 2025
Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
Identifying targetable alterations predictive of distant progression in glioblastoma patients undergoing standard
Shivani Chiranth1, Vincent Fougner1,2, Ib Jarle Christensen1
1The DCCC Brain Tumor Center, Rigshospitalet, Copenhagen, Denmark.
Background:
Infiltrative growth is a hallmark of glioblastoma (GBM) and is a major factor in therapeutic failure. Distant progression is a surrogate marker for infiltrative growth and genetic variants predictive of distant progression may serve as novel treatment targets. The aim was to identify clinical, molecular, radiographic, and genetic factors associated with distant progression in GBM patients.
Methods:
From our prospective database, all consecutive GBM IDH wild type patients receiving standard therapy (Stupp regimen) from 2016 to 2021 at Rigshospitalet (Denmark) were included. Distant progression was defined as a new contrast-enhancing lesion > 2 cm from the initial lesion. Clinical, molecular, radiographic, and genomic covariates were assessed for association with time to distant progression using Cox analysis.
Results:
This single-center study included 353 patients, of whom 303 patients had radiographic progression. Distant progression was found in 66 patients (22%) and was associated with poor post-progression survival (P < .001). Unmethylated MGMT (hazard ratio [HR]: 2.54, 95% confidence interval [CI]: 1.62-3.97, P < .001), and multicentric disease at diagnosis (HR: 2.32, 95% CI: 1.28-4.20, P = .005) were associated with a shorter time to distant progression. In patients with a genomic tumor profile (n = 204), the NF1 gene alteration was identified as an independent predictor of distant progression (HR: 3.48, 95% CI: 1.48-8.21, P = .004) and poor survival.
Conclusion:
Distant progression is an aggressive progression pattern associated with a poor prognosis. Unmethylated MGMT, multicentric disease, and NF1 alteration independently predict distant progression. NF1 alteration may serve as a predictive biomarker for targeted treatment.
