Depressive symptoms and executive function in relation to survival in patients with glioblastoma.

INTRODUCTION: Depression and neurocognitive function, particularly executive functioning (EF), have been associated with overall survival (OS) in patients with glioblastoma (GBM). However, the combined effect of depressive symptoms and impaired EF upon OS has not been reported. METHODS: Patients with GBM (N = 102) completed neuropsychological assessment postoperatively, including the Beck Depression Inventory-Second Edition (BDI-II) and the Trail Making Test Part B (TMTB). Median splits were used to determine cut-points denoting elevated depressive symptoms on the BDI-II and impaired EF on TMTB. Patients were stratified into four groups: low depressive symptoms/low EF impairment (- Dep/- Imp; N = 23), high depressive symptoms/low EF impairment (+ Dep/- Imp; N = 28), low depressive symptoms/high EF impairment (- Dep/+Imp; N = 28), and high depressive symptoms/high EF impairment (+ Dep/+Imp; N = 23). The Kaplan-Meier method, log-rank test, and Cox regression were used to examine differences in survival between groups. RESULTS: Relative to - Dep/- Imp patients (median OS = 22.8 months), median OS in all other patient groups was shorter (+ Dep/- Imp OS = 16.6; - Dep/+Imp OS = 14.8; +Dep/+Imp OS = 10.8; all p < .05). With the exception of KPS and age, groups did not differ in distribution of clinical and demographic characteristics. Neither KPS nor age modified the independent effect of BDI-II and TMTB on OS in Cox regression models. CONCLUSIONS: The presence of depressive symptoms and impaired EF are independently associated with shorter OS in patients with GBM. These results suggest that routine neuropsychological assessment of mood and cognition may help refine prognosis and facilitate initiation of psychological and cognitive interventions, which can improve patient quality of life, and warrants further investigation.

Neurocognitive dysfunction in adult cerebellar medulloblastoma.

OBJECTIVE: Impaired neurocognitive function (NCF) is a well-established consequence of pediatric medulloblastoma (MB) and its treatments. However, the frequency and features of neurocognitive dysfunction in adult-onset MB patients are largely unknown. METHODS: Adult patients (≥ 18 years) with MB who had received formal neurocognitive evaluation (N = 27) were identified. Demographic, medical, and treatment histories were extracted from the medical record. Lesion properties on MRI were analyzed and used to evaluate lesion-symptom mapping further. Demographically adjusted z-scores were calculated for each neurocognitive test and used to assess impairment frequency. Regression analyses were conducted to identify clinical and paraclinical factors associated with impaired NCF. RESULTS: Mean age of the patient sample was 33 years (SD = 11) at the time of MB diagnosis. Prior therapy included surgical resection (89%), radiation (70%), and chemotherapy (26%). A significant proportion of patients were impaired on tests of verbal learning and memory (32%), executive function (29%), and naming (18%). Age, education, lesion size, time from surgery, and number of chemotherapy cycles had the greatest contribution to test performance in random-forest regression models. CONCLUSION: This study identifies frequent impairment of NCF in adult patients with MB, particularly in the domains of learning and memory and executive function. Neurocognitive impairment is influenced by patients' demographic, disease, and treatment history. Further study is warranted to characterize the clinical impact of adult MB more fully.

Association of genetic variants with fatigue in patients with malignant glioma.

BACKGROUND: Fatigue is a consistently reported, severe symptom among patients with gliomas throughout the disease trajectory. Genomic pathways associated with fatigue in glioma patients have yet to be identified. METHODS: Clinical factors (performance status, tumor details, age, gender) were collected by chart review on glioma patients with fatigue ("I have lack of energy" on Functional Assessment of Cancer Therapy-Brain), as well as available genotyping data. Candidate genes in clock and inflammatory pathways were identified from a literature review, of which 50 single nucleotide polymorphisms (SNPs) in 7 genes were available. Clinical factors and SNPs identified by univariate analyses were included in a multivariate model for moderate-severe fatigue. RESULTS: The study included 176 patients (median age = 47 years, 67% males). Moderate-severe fatigue was reported by 43%. Results from multivariate analysis revealed poor performance status and 2 SNPs were associated with fatigue severity. Moderate-severe fatigue was more common in patients with poor performance status (OR = 3.52, P < .01). For each additional copy of the minor allele in rs934945 (PER2) the odds of fatigue decreased (OR = 0.51, P < .05). For each additional copy of the minor allele in rs922270 (ARTNL2) the odds of fatigue increased (OR = 2.38, P < .01). Both of these genes are important in the circadian clock pathway, which has been implicated in diurnal preference, and duration and quality of sleep. No genes in the inflammatory pathway were associated with fatigue in the current study. CONCLUSIONS: Identifying patients at highest risk for fatigue during treatment allows for improved clinical monitoring and enrichment of patient selection for clinical trials.