Identifying targetable alterations predictive of distant progression in glioblastoma patients undergoing standard therapy.

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 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 ( < .001). Unmethylated (hazard ratio [HR]: 2.54, 95% confidence interval [CI]: 1.62-3.97,  < .001), and multicentric disease at diagnosis (HR: 2.32, 95% CI: 1.28-4.20,  = .005) were associated with a shorter time to distant progression. In patients with a genomic tumor profile ( = 204), the gene alteration was identified as an independent predictor of distant progression (HR: 3.48, 95% CI: 1.48-8.21,  = .004) and poor survival.

CONCLUSION

Distant progression is an aggressive progression pattern associated with a poor prognosis. Unmethylated multicentric disease, and alteration independently predict distant progression. alteration may serve as a predictive biomarker for targeted treatment.