The role of alteration and 4q12 amplification in IDH-WT glioblastoma.

Background: Recent studies have identified that glioblastoma IDH-wildtype (GBM IDH-WT) might be comprised of molecular subgroups with distinct prognoses. Therefore, we investigated the correlation between genetic alterations and survival in 282 GBM IDH-WT patients, to identify subgroups with distinct outcomes.

Methods: We reviewed characteristics of GBM IDH-WT (2009-2019) patients analyzed by next-generation sequencing interrogating 205 genes and 26 rearrangements. Progression-free survival (PFS) and overall survival (OS) were evaluated with the log-rank test and Cox regression models. We validated our results utilizing data from cBioPortal (MSK-IMPACT dataset).

Results: Multivariable analysis of GBM IDH-WT revealed that treatment with chemoradiation and mutant status correlated with improved PFS (hazard ratio [HR] 0.25, < .001 and HR 0.47, = .002) and OS (HR 0.24, < .001 and HR 0.49, = .016). In addition, younger age (<55 years) was associated with improved OS. Karnofsky performance status less than 80 (HR 1.44, = .024) and amplification (HR 2.51, = .008) were predictors of worse OS. amplified patients harbored coexisting and amplification ( < .001) and mutations ( = .04). mutant patients had less frequent and alterations ( < .001). Conversely, mutant patients had more frequent ( < .001) and ( = .006) mutations. Analysis of the MSK-IMPACT dataset ( = 551) validated the association between mutations and improved PFS (11.0 vs 8.7 months, .009) and OS (34.7 vs 21.7 months, .016).

Conclusions: -mutant GBM IDH-WT is a molecular subgroup with improved PFS and OS. Meanwhile, 4q12 amplification ( denoted patients with worse OS. Identifying subgroups of GBM IDH-WT with distinct survival is important for optimal clinical trial design, incorporation of targeted therapies, and personalized neuro-oncological care.