Project description:PurposeBrain metastases (BM) themselves and treatment with stereotactic radiosurgery (SRS) can influence neurocognitive functioning. This prospective study aimed to assess neurocognitive decline in patients with BM after SRS.MethodsA neuropsychological test battery was assessed yielding ten test outcomes. Neurocognitive decline at 3 and 6 months post SRS was compared to measurement prior to Gamma Knife (GK) or linear accelerator (LINAC) SRS. Reliable change indices with correction for practice effects were calculated to determine the percentage of neurocognitive decline (defined as decline on ≥ 2 test outcomes). Risk factors of neurocognitive decline were analyzed with binary logistic regression.ResultsOf 194 patients pre-SRS, 40 GK and 29 LINAC patients had data accessible at 6 months. Compared to baseline, 38% of GK patients declined at 3 months, and 23% declined at 6 months. GK patients declined on attention, executive functioning, verbal memory, and fine motor skill. Of LINAC patients, 10% declined at 3 months, and 24% at 6 months. LINAC patients declined on executive functioning, verbal memory, and fine motor skills. Risk factors of neurocognitive decline at 3 months were high age, low education level and type of SRS (GK or LINAC). At 6 months, high age was a risk factor. Karnofsky Performance Scale, BM volume, number of BM, tumor progression and neurocognitive impairment pre-SRS were no risk factors.ConclusionNeurocognitive decline occurs in a considerable proportion of patients with BM treated with GK or LINAC SRS. Overall, high age appears to be a risk factor for neurocognitive decline after SRS.
Project description:BackgroundStereotactic radiotherapy (SRT) is expected to have a less detrimental effect on neurocognitive functioning and health-related quality of life (HRQoL) than whole-brain radiotherapy. To evaluate the impact of brain metastases and SRT on neurocognitive functioning and HRQoL, we performed a prospective study.MethodsNeurocognitive functioning and HRQoL of 97 patients with brain metastases were measured before SRT and 1, 3, and 6 months after SRT. Seven cognitive domains were assessed. HRQoL was assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and BN20 questionnaires. Neurocognitive functioning and HRQoL over time were analyzed with linear mixed models and stratified for baseline Karnofsky performance status (KPS), total metastatic volume, and systemic disease.ResultsMedian overall survival of patients was 7.7 months. Before SRT, neurocognitive domain and HRQoL scores were lower in patients than in healthy controls. At group level, patients worsened in physical functioning and fatigue at 6 months, while other outcome parameters of HRQoL and cognition remained stable. KPS < 90 and tumor volume >12.6 cm(3) were both associated with worse information processing speed and lower HRQoL scores over 6 months time. Intracranial tumor progression was associated with worsening of executive functioning and motor function.ConclusionsPrior to SRT, neurocognitive functioning and HRQoL are moderately impaired in patients with brain metastases. Lower baseline KPS and larger tumor volume are associated with worse functioning. Over time, SRT does not have an additional detrimental effect on neurocognitive functioning and HRQoL, suggesting that SRT may be preferred over whole-brain radiotherapy.
Project description:Background & Objectives: Radiotherapy is standard treatment for patients with brain metastases (BMs), although it may lead to radiation-induced cognitive impairment. This review explores the impact of whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) on cognition.MethodsThe PRISMA guidelines were used to identify articles on PubMed and EmBase reporting on objective assessment of cognition before, and at least once after radiotherapy, in adult patients with nonresected BMs.ResultsOf the 867 records screened, twenty articles (14 unique studies) were included. WBRT lead to decline in cognitive performance, which stabilized or returned to baseline in patients with survival of at least 9-15 months. For SRS, a decline in cognitive performance was sometimes observed shortly after treatment, but the majority of patients returned to or remained at baseline until a year after treatment.ConclusionsThese findings suggest that after WBRT, patients can experience deterioration over a longer period of time. The cognitive side effects of SRS are transient. Therefore, this review advices to choose SRS as this will result in lowest risks for cognitive adverse side effects, irrespective of predicted survival. In an already cognitively vulnerable patient population with limited survival, this information can be used in communicating risks and aid in making educated decisions.
Project description:ObjectiveChildren with acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits, and examining individual variability is essential to understand these risks. This study evaluated latent longitudinal trajectories and risk factors of neurocognitive outcomes in childhood ALL.MethodsThere were 233 participants with ALL who were enrolled on a phase 3, risk-stratified chemotherapy-only clinical trial (NCT00137111) and who completed protocol-directed neurocognitive assessments [47.6% female, mean (SD) = 6.6 (3.7) years]. Measures of sustained attention, learning/memory, and parent ratings of attention were completed during and after treatment. Longitudinal latent class analyses were used to classify participants into distinct trajectories. Logistic regression was used to identify predictors of class membership.ResultsWithin the overall group, attention performance was below age expectations across time (Conners Continuous Performance Test detectability/variability, p < 0.01); memory performance and parent ratings were below expectations at later phases (California Verbal Learning Test learning slope, p < 0.05; Conners Parent Rating Scale, Revised attention/learning, p < 0.05). Most participants (80-89%) had stable neurocognitive profiles; smaller groups showed declining (3-6%) or improving (3-11%) trajectories. Older age (p = 0.020), female sex (p = 0.018), and experiencing sepsis (p = 0.047) were associated with greater attention problems over time. Lower baseline IQ was associated with improved memory (p = 0.035) and fewer ratings of attention problems (p = 0.013) over time.ConclusionsMost patients with ALL have stable neurocognitive profiles. Smaller groups have significant impairments shortly after diagnosis or have worsening performance over time. A tiered assessment approach, which includes consideration of individual and clinical risk factors, may be useful for monitoring neurocognitive functioning during treatment and survivorship.
Project description:Impairment of neurocognitive functioning is a common result of cerebral neoplasms and treatment, although there is substantial heterogeneity in the pattern and severity of neurocognitive dysfunction across individuals and tumour types. The effects of many clinical and patient characteristics on neurocognitive functioning have been documented, but little research has been devoted to understanding the effect of genetic variation on neurocognitive outcomes in patients with brain tumours. This Review highlights preliminary evidence that suggests an association between various genes and risk of adverse neurocognitive outcomes in patients with brain tumours. Studies include genes specific to neuronal function, and those associated with more systemic cellular regulation. Related scientific literature in other disease populations is briefly discussed to indicate additional candidate genes. We consider methodological issues central to the study of neurocognitive functioning and genetic associations for patients with brain tumours, and emphasise the need for future research integrating novel investigative techniques.
Project description:Whole brain radiation therapy (WBRT) is an effective treatment in brain metastases and, when combined with local treatments such as surgery and stereotactic radiosurgery, gives the best brain control. Nonetheless, WBRT is often omitted after local treatment due to its potential late neurocognitive effects. Publications on radiation-induced neurotoxicity have used different assessment methods, time to assessment, and definition of impairment, thus making it difficult to accurately assess the rate and magnitude of the neurocognitive decline that can be expected. In this context, and to help therapeutic decision making, we have conducted this literature review, with the aim of providing an average incidence, magnitude and time to occurrence of radio-induced neurocognitive decline. We reviewed all English language published articles on neurocognitive effects of WBRT for newly diagnosed brain metastases or with a preventive goal in adult patients, with any methodology (MMSE, battery of neurcognitive tests) with which baseline status was provided. We concluded that neurocognitive decline is predominant at 4 months, strongly dependant on brain metastases control, partially solved at later time, graded 1 on a SOMA-LENT scale (only 8% of grade 2 and more), insufficiently assessed in long-term survivors, thus justifying all efforts to reduce it through irradiation modulation.
Project description:Neurocognitive function (NCF) deficits are common in patients with brain metastases, occurring in up to 90% of cases. NCF deficits may be caused by tumor-related factors and/or treatment for the metastasis, including surgery, radiation therapy, chemotherapy, and immunotherapy. In recent years, strategies to prevent negative impact of treatments and ameliorate cognitive deficits for patients with brain tumors have gained momentum. In this review, we report on research that has established the efficacy of preventative and rehabilitative therapies for NCF deficits in patients with brain metastases. Surgical strategies include the use of laser interstitial thermal therapy and intraoperative mapping. Radiotherapy approaches include focal treatments such as stereotactic radiosurgery and tailored approaches such as hippocampal avoidant whole-brain radiotherapy (WBRT). Pharmacologic options include use of the neuroprotectant memantine to reduce cognitive decline induced by WBRT and incorporation of medications traditionally used for attention and memory problems. Integration of neuropsychology into the care of patients with brain metastases helps characterize cognitive patterns, educate patients and families regarding their management, and guide rehabilitative therapies. These and other strategies will become even more important for long-term survivors of brain metastases as treatment options improve.
Project description:IntroductionIn seizure-naive brain tumor patients, the efficacy of perioperative prophylactic antiepileptic drug treatment remains controversial. In case of administration, the common preferred drug is levetiracetam (LEV) because of its favorable pharmacological profile. Research to date has not sufficiently determined how LEV affects cognition in the short term, as is the case in the perioperative period. The objective of this prospective study was to examine the neurocognitive functioning of seizure-naive brain tumor patients after receiving LEV perioperatively.MethodsFortythree patients with supratentorial brain tumor scheduled for surgery received LEV three days before until six days after surgery as seizure prophylaxis. Cognitive functioning (NeuroCogFX), LEV plasma-levels, hematotoxicity, side-effects, as well as health-related quality of life (HRQoL, Qolie31), were recorded preoperatively before (Baseline) and after onset of LEV (Pre-Op), 4-6 days postoperatively (Post-Op) and 21 days postoperatively (Follow-Up).ResultsNo significant changes in cognitive functioning and HRQoL were seen after onset of preoperative LEV. There was a significant improvement of NeuroCogFX total-score at Follow-Up (p = 0.004) compared to Baseline. The overall-score Qolie31 showed simultaneous improvement patterns as cognitive functioning (p < 0.001). The most frequent side effect related to study drug was somnolence (in 28.6% of patients).ConclusionsA significant improvement of cognitive functioning, as well as an improvement in HRQoL, were detected postoperatively. This is presumably due to the debulking effect of the surgery. Nevertheless, LEV has no detrimental effect on cognitive functioning in the perioperative phase in seizure-naive brain tumor patients.Trial registrationThis study was registered prospectively (Date: 25/11/2015; EudraCT: 2015-003,916-19).
Project description:BackgroundWhole-brain radiotherapy (WBRT) used to be standard of care for patients suffering from melanoma brain metastases (MBM) and may still be applicable in selected cases. Deterioration of neurocognitive function (NCF) is commonly seen during and after WBRT. Knowledge on long-term effects in melanoma patients is limited due to short survival rates. With the introduction of immune checkpoint inhibitors, patients may experience ongoing disease control, emphasizing the need for paying more attention to potential long-term adverse effects.MethodsIn this single-center study, we identified in a period of 11 years all long-term survivors of MBM who received WBRT at least 1 year prior to inclusion. NCF was assessed by Neuropsychological Assessment Battery (NAB) screening and detailed neurological exam; confounders were documented.ResultsEight patients (median age 55 years) could be identified with a median follow-up of 5.4 years after WBRT. Six patients reported no subjective neurological impairment. NAB screening revealed an average-range score in 5/8 patients. In 3/8 patients a NAB score below average was obtained, correlating with subjective memory deficits in 2 patients. In these patients, limited performance shown in modalities like memory function, attention, and spatial abilities may be considerably attributed to metastasis localization itself. Six out of 8 patients were able to return to their previous work.ConclusionFive of 8 long-term survivors with MBM after WBRT experienced little to no restriction in everyday activities. In 3 out of 8 patients, cognitive decline was primarily explained by localization of the metastases in functionally relevant areas of the brain. The results of our small patient cohort do not support general avoidance of WBRT for treatment of brain metastases. However, long-term studies including pretreatment NCF tests are needed to fully analyze the long-term neurocognitive effects of WBRT.
Project description:PURPOSE:Information on predictive factors of cognitive functioning in patients with (multiple) brain metastases (BM) selected for radiosurgery may allow for more individual care and may play a role in predicting cognitive outcome after radiosurgery. The aim of this study was to evaluate cognitive performance, and predictors thereof, in patients with 1-10 BM before radiosurgery. METHODS:Cognition was measured before radiosurgery using a standardized neuropsychological test battery in patients with 1-10 BM (expected survival > 3 months; KPS ≥ 70; no prior BM treatment). Regression formulae were constructed to calculate sociodemographically corrected z scores. Group and individual cognitive functioning was analyzed. Multivariable regression was used to explore potential predictors. RESULTS:Patients (N = 92) performed significantly worse than controls (N = 104) on all 11 test variables (medium-large effect sizes for 8 variables). Percentages of impairment were highest for information processing (55.3%), dexterity (43.2%) and cognitive flexibility (28.7%). 62% and 46% of patients had impairments in at least two, or three test variables, respectively. Models including combinations of clinical and psychological variables were predictive of verbal memory, psychomotor speed, information processing and dexterity. Neither number nor volume of metastases predicted patients' test performance. CONCLUSIONS:Already before radiosurgery, almost half of the patients suffered from severe cognitive deficits in at least three test variables. At group and individual level, information processing, cognitive flexibility, and dexterity were most affected. These cognitive impairments may impair daily functioning and patients' ability to make (shared) treatment decisions. Both clinical (symptomatic BM; timing of BM diagnosis) and psychological (mental fatigue) characteristics influenced cognitive performance. CLINICAL TRIAL INFORMATION:Cognition and Radiation Study A (CAR-Study A; ClinicalTrials.gov Identifier: NCT02953756; Medical Ethics Committee file number: NL53472.028.15/P1515).