Corticosteroids use and neurocognitive functioning in patients with recurrent glioblastoma: Evidence from European Organization for Research and Treatment of Cancer (EORTC) trial 26101

Abstract

Background In patients with recurrent glioblastoma corticosteroids are frequently used to mitigate intracranial pressure and to improve patient neurological functioning. To date, in these patients no systematic studies have been performed to assess neurocognitive functioning (NCF) in relation to corticosteroid treatment. Methods Using baseline data (i.e., prior to randomization) of EORTC trial 26101 we performed regression analysis to assess the predictive value of corticosteroids intake on performance of the EORTC brain tumor clinical trial NCF test battery. The battery is comprised of the Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association test (COWA) and Trail Making Test (A and B). Results Out of 321 patients 148 (46.1%) were not using corticosteroids, and 173 were using dexamethasone (34.3%), methylprednisolone (9.7%) or other corticosteroids (9.9%). Patients on corticosteroids had worse performance on all neurocognitive tests. Regression analyses demonstrated a negative association between corticosteroids use and the HVLT-R Free Recall score (R² change = 0.034, F change (1,272) = 13.392, p<.001) and HVLT-R Delayed Recall score (R² change = 0.028, F change (1,270) = 10.623 p=.002). No statistically significant association was found for HVLT-R Delayed recognition, COWA, TMT part A and TMT part B (p>0.05). Conclusions Glioblastoma patients prescribed with corticosteroids show poorer memory functions, expressive language, visual-motor scanning speed and executive functioning than patients not using corticosteroids. Furthermore, we found a negative association between corticosteroid intake and memory functions. The possibility of deleterious effects of corticosteroids on NCF should be considered during clinical decision-making.

Influences on cognitive outcomes in adult patients with gliomas: A systematic review

“…There is evidence from patients with HGG, however, that corticosteroid use is associated with improved recognition memory, which is likely to be due to resolution of cerebral oedema ( 49 ). The most robust evidence on corticosteroid use comes from an analysis of data collected from an RCT that effect of corticosteroid use on neurocognitive function in 321 patients with recurrent glioblastoma, using data from the European Organization for Research and Treatment of Cancer trial 26101; it found that patients on corticosteroids had worse neurocognitive function in all tested domains (memory, expressive language, visual-motor scanning speed, executive functioning) compared to those not on corticosteroids with significant inverse correlations between corticosteroid use and Hopkins Verbal Learning Test - Revised Free Recall and Delayed Recall scores ( 161 ). There is limited evidence of the effect of corticosteroids on cognition in patients with LGG, which is likely to be due at least in part to the fact that LGGs tend to cause cerebral oedema less frequently than many other tumor types.…”

Diabetes Mellitus Management in the Context of Cranial Tumors

“…Furthermore, Caramanna showed that corticosteroid use was linked to poorer outcomes in memory function, expressive language, and executive function compared to GBS cohorts not using corticosteroids [97]. Accordingly, many clinical trials for GBS have corticosteroid use as an exclusion criterion.…”

Regulation of cancer stem cells and immunotherapy of glioblastoma (Review)

“…In fact, the exhausted phenotype of immunocytes is developed due to the GB cells producing PD-L1 and 2, CTLA-4 and other proteins that inhibit T-cell activity receptors ( 144 ). The emergence of a new class of drugs that prevent PD-ligands from binding to T-cell receptors has attracted interest ( 145 ), but the effectiveness of nivolumab and other immune checkpoint inhibitors in the complex treatment of GB was revealed to be low ( 146 ), thus suggesting the existence of other causes of systemic immunosuppression.…”