Neurocognitive functioning in long-term survivors of glioblastoma, IDH-wildtype and astrocytoma, IDH-mutant, CNS WHO grade 4: A report from EORTC 1419 (ETERNITY).

BACKGROUND

ETERNITY was a retrospective and prospective cohort study investigating long-term (≥5 years) survival in patients with glioblastoma. We assessed the longitudinal course of neurocognitive function (NCF) and its determinants in a subgroup of patients with glioblastoma, IDH-wildtype, or astrocytoma, IDH-mutant, CNS WHO grade 4.

METHODS

NCF was assessed at baseline and every 6 months using the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association Test, and Trail Making Test. Scores were converted to age-, sex-, and education-adjusted Z-scores and classified as impaired or unimpaired (Z ≤ -1.5). Linear mixed models were used to analyze NCF trajectories and associations with patient and tumor characteristics.

RESULTS

At baseline (mean 9 years post-diagnosis, range 5-21 years), 145 of 185 patients (78%) were impaired on ≥1 test outcome. Impairment rates varied between 17.4% (HVLT-R delayed recognition) and 58.7% (TMT B). NCF remained largely stable over time, with a small decline in HVLT-R delayed memory. Left-sided and temporal tumor location were negatively associated with poorer NCF (p's.01 to.03). Frontal tumor location was associated with higher psychomotor speed and cognitive flexibility (p's <.001). Patients with IDH-mutant tumors performed worse on delayed recognition, whereas IDH mutation and MGMT promoter methylation were linked to improved phonemic fluency over time.

CONCLUSIONS

The majority of long-term survivors with astrocytoma, IDH-mutant, CNS WHO grade 4, and glioblastoma IDH-wildtype show neurocognitive impairment. Nonetheless, NCF is generally stable, with tumor location and molecular features associated with specific outcomes. These insights can help guide patient counseling and personalized care.