Association between objective neurocognitive functioning and neurocognitive complaints in recurrent high-grade glioma: Longitudinal evidence of cognitive awareness from EORTC brain tumour trials.

BACKGROUND: Patients' reduced awareness of neurocognitive functioning (NCF) may negatively affect the reliability of patient-reported outcomes (PROs) and clinical decision-making. This study evaluated cognitive awareness, defined as the association between NCF and neurocognitive complaints, over the disease course of patients with recurrent high-grade glioma (HGG). METHODS: We assessed NCF using the EORTC core clinical trial battery and neurocognitive complaints using the Medical Outcome Study questionnaire. Patients were categorised as impaired or intact, based on their neurocognitive performance. Spearman's rank correlations were calculated between NCF and neurocognitive complaints at baseline and each 12 weeks, until 36. The association between changes in NCF and neurocognitive complaints scores between these follow-up assessments was determined using Pearson's correlation. RESULTS: A total of 546 patients were included. Neurocognitively impaired patients (n = 437) had more neurocognitive complaints (range: 10.51 [p < 0.001] to 13.34 [p = 0.001]) than intact patients (n = 109) at baseline, at 12 and 24 weeks. In intact patients, NCF and neurocognitive complaints were correlated for only one domain at baseline (0.202, p = 0.036), while in impaired patients correlations were more frequently found in various domains and time points (range: 0.164 [p = 0.001] to 0.334 [p = 0.011]). Over the disease course, NCF and neurocognitive complaints were correlated for only one domain at baseline (0.357, p = 0.014) in intact patients while in impaired patients they were correlated for more domains and time points (range: 0.222 [p < 0.001] to 0.366 [p < 0.001]). CONCLUSION: Neurocognitively impaired patients with recurrent HGG are aware of their neurocognitive limitations at study entry and during follow-up, which should be considered in clinical decision-making and when interpreting PRO results.

Neurocognitive impairment and patient-proxy agreement on health-related quality of life evaluations in recurrent high-grade glioma patients.

PURPOSE: The rate of missing data on patient-reported health-related quality of life (HRQOL) in brain tumor clinical trials is particularly high over time. One solution to this issue is the use of proxy (i.e., partner, relative, informal caregiver) ratings in lieu of patient-reported outcomes (PROs). In this study we investigated patient-proxy agreement on HRQOL outcomes in high-grade glioma (HGG) patients. METHODS: Generic and disease-specific HRQOL were assessed using the EORTC QLQ-C30 and QLQ-BN20 in a sample of 501 patient-proxy dyads participating in EORTC trials 26101 and 26091. Patients were classified as impaired or intact, based on their neurocognitive performance. The level of patient-proxy agreement was measured using Lin's concordance correlation coefficient (CCC) and the Bland-Altman limit of agreement. The Wilcoxon signed-rank test was used to evaluate differences between patients' and proxies' HRQOL. RESULTS: Patient-proxy agreement in all HGG patients (N = 501) ranged from 0.082 to 0.460. Only 18.8% of all patients were neurocognitively intact. Lin's CCC ranged from 0.088 to 0.455 in cognitively impaired patients and their proxies and from 0.027 to 0.538 in cognitively intact patients and their proxies. CONCLUSION: While patient-proxy agreement on health-related quality of life outcomes is somewhat higher in cognitively intact patients, agreement in high-grade glioma patients is low in general. In light of these findings, we suggest to cautiously consider the use of proxy's evaluation in lieu of patient-reported outcomes, regardless of patient's neurocognitive status.

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

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 (ie, prior to randomization) of European Organization for Research and Treatment of Cancer (EORTC) trial 26101, we performed regression analysis to assess the predictive value of corticosteroid 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 (R 2 change = 0.034, F change (1, 272) = 13.392, P < .001) and HVLT-R Delayed Recall score (R 2 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 > .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.

Objective neurocognitive functioning and neurocognitive complaints in patients with high-grade glioma: Evidence of cognitive awareness from the European Organisation for Research and Treatment of Cancer brain tumour clinical trials.

BACKGROUND: Neurocognitively impaired patients with brain tumour are presumed to have reduced cognitive awareness preventing them from adequately valuing and reporting their own functioning, for instance, when providing patient-reported outcomes (PROs) such as health-related quality of life instruments. In this cross-sectional study, we aimed at assessing the concordance of neurocognitive complaints (NCCs) and objective neurocognitive functioning (NCF) as a measure of cognitive awareness. METHODS: NCF was assessed using an internationally accepted clinical trial battery. NCC was assessed using the cognitive functioning questionnaire from the Medical Outcome Study (MOS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire cognitive functioning subscale. Patients were divided in cognitively impaired and unimpaired groups, based on their NCF performance. Pearson's correlation coefficients between NCF and NCCs were calculated. The same procedure was used to evaluate the correlation of NCF and QLQ-C30 CF subscale. RESULTS: Data from EORTC trials 26091 and 26101 were pooled into a data set of 546 patients. Twenty percent of patients could be characterised as unimpaired (109) and 80% as impaired (437). Impaired patients reported more cognitive complaints on the MOS scale than unimpaired patients. Correlations between NCF and NCCs were weak but significant for impaired patients and non-significant for unimpaired ones. Similar results were found for the correlation between NCF test performance and the QLQ-C30 CF subscale. CONCLUSION: Correlations between NCF test scores and complaints were weak but suggesting that neurocognitive impairment in patients with HGG does not preclude cognitive awareness. However, considering the findings of this study, we would suggest not to use PROs as a surrogate of performance-based neurocognitive evaluation.