Perioperative executive functioning in patients with low-grade gliomas near the Frontal Aslant Tract

Background A tract potentially involved in important executive cognitive processes is the Frontal Aslant Tract (FAT). In particular the right FAT has been associated with executive functioning (EF). In neurosurgery, it remains unclear if patients with tumors near the FAT demonstrate EF impairments after resection. This study investigated whether low grade gliomas (LGG) that affect the core white matter and/or structural integrity of the FAT predict preoperative and 3 months postoperative EF, when controlled for tumor volume and the integrity of other nearby tracts (SLF II and SLF III). Material and Methods Data was analyzed from patients with frontal and parietal LGG who underwent surgery between 2010-2021. Probabilistic tractography was performed prior to surgery to generate preoperative tracts of the FAT, SLF II and SLF III. The core of the FAT was defined as the white matter between the seed and the target region. Average mean diffusivity for each tract was taken as a measure of structural integrity. EF was assessed one day before and 3 months post-surgery with the following tests: Stroop test, symbol digit coding test (SDC), shifting attention test (SAT), and letter fluency test (LF). We performed linear mixed models and linear regression analyses to investigate the relationship between presurgical tumor overlap with the core of the FAT and FAT integrity with pre- and postsurgical executive test performances. Results Seventy-five patients were included (left tumor N=39, right tumor N=36). Mean pre-surgical Z-scores were within 0.5 standard deviation from a healthy control group for all tests, but with substantial variance between patients (Z-score range:-3.59 to 2.4). The results demonstrated that core overlap of the right FAT predicted preoperative performance on the SAT (p<.01, β= -.473), Stroop (p<.01, β= -.519), and SDC (p<.01, β= -.519). Right or left core overlap did not significantly predict performance three months after surgery. FAT integrity did not predict preoperative EF performance, whereas it did predict SAT performance at three months post-surgical (p<.01, β= -.694) when controlled for SLF II, III integrity and tumor volume. Conclusion Although patients with frontal or parietal LGG showed no dysfunction on tests of EF before surgery on group level, they demonstrated large variability between patients. Tumor overlap with the core of the right FAT predicted worse presurgical EF performances, but not short-term post-surgical performances. Right FAT integrity predicted short-term post-surgical performance on cognitive flexibility. These results are in line with previous findings that the right FAT is involved in EF and indicate that preoperative FAT integrity might predict which patients will perform worse after surgery

Group and individual change in cognitive functioning in patients with 1 to 10 brain metastases following Gamma Knife radiosurgery

Aims:  Stereotactic radiosurgery is increasingly used to treat multiple (four or more) brain metastases. Preserving cognitive functions is a highly relevant treatment goal because cognitive deteriorations may negatively affect a patient's quality of life. The aim of this study was to assess cognitive change, at the group and individual level, in patients with 1 to 10 brain metastases up to 9 months after Gamma Knife radiosurgery (GKRS). Materials and methods:  Ninety-two patients with 1 to 10 newly diagnosed brain metastases, expected survival >3 months and Karnofsky Performance Status (KPS) ≥70 and 104 non-cancer controls were included. A neuropsychological test battery was administered before GKRS (n = 92) and at 3 (n = 66), 6 (n = 52) and 9 (n = 41) months after GKRS. The course of test performances, while taking into account practice effects, was analysed using linear mixed models. Pre-GKRS predictors of cognitive trajectories were analysed. To determine proportions of individuals with cognitive changes, reliable change indices, with correction for practice effects, were calculated. Results:  At the group level, immediate memory, working memory and information processing speed significantly improved over 9 months after GKRS. There were no cognitive declines. Neither number nor volume of brain metastases influenced cognitive change over time. At the individual level, proportions of patients with stable, improved or declined performances were comparable with controls, except for information processing speed (more individuals with improvements in patients) and motor dexterity (more improvements and declines in patients). Conclusions:  Cognitive functioning in patients with 1 to 10 brain metastases was preserved, or improved, up to 9 months after GKRS. Neither number nor volume of brain metastases influenced cognitive performance

Factors associated with the local control of brain metastases:A systematic search and machine learning application

Background: Enhancing Local Control (LC) of brain metastases is pivotal for improving overall survival, which makes the prediction of local treatment failure a crucial aspect of treatment planning. Understanding the factors that influence LC of brain metastases is imperative for optimizing treatment strategies and subsequently extending overall survival. Machine learning algorithms may help to identify factors that predict outcomes. Methods: This paper systematically reviews these factors associated with LC to select candidate predictor features for a practical application of predictive modeling. A systematic literature search was conducted to identify studies in which the LC of brain metastases is assessed for adult patients. EMBASE, PubMed, Web-of-Science, and the Cochrane Database were searched up to December 24, 2020. All studies investigating the LC of brain metastases as one of the endpoints were included, regardless of primary tumor type or treatment type. We first grouped studies based on primary tumor types resulting in lung, breast, and melanoma groups. Studies that did not focus on a specific primary cancer type were grouped based on treatment types resulting in surgery, SRT, and whole-brain radiotherapy groups. For each group, significant factors associated with LC were identified and discussed.. As a second project, we assessed the practical importance of selected features in predicting LC after Stereotactic Radiotherapy (SRT) with a Random Forest machine learning model. Accuracy and Area Under the Curve (AUC) of the Random Forest model, trained with the list of factors that were found to be associated with LC for the SRT treatment group, were reported.Results: The systematic literature search identified 6270 unique records. After screening titles and abstracts, 410 full texts were considered, and ultimately 159 studies were included for review. Most of the studies focused on the LC of the brain metastases for a specific primary tumor type or after a specific treatment type. Higher SRT radiation dose was found to be associated with better LC in lung cancer, breast cancer, and melanoma groups. Also, a higher dose was associated with better LC in the SRT group, while higher tumor volume was associated with worse LC in this group. The Random Forest model predicted the LC of brain metastases with an accuracy of 80% and an AUC of 0.84. Conclusion: This paper thoroughly examines factors associated with LC in brain metastases and highlights the translational value of our findings for selecting variables to predict LC in a sample of patients who underwent SRT. The prediction model holds great promise for clinicians, offering a valuable tool to predict personalized treatment outcomes and foresee the impact of changes in treatment characteristics such as radiation dose.<br/

Cognitive complaints in patients with untreated obstructive sleep apnea versus patients with neurological and respiratory diseases:Prevalence, severity and risk factors

PurposeLittle is known about cognitive complaints (self-reported problems in cognitive functioning) in patients with Obstructive Sleep Apnea (OSA). We compared the prevalence and severity of cognitive complaints in patients with untreated OSA to patients with neurological and respiratory diseases. We also studied risk factors for cognitive complaints across these diseases, including OSA.MethodsWe used a convenience sample to compare untreated OSA patients (N = 86) to patients with stroke (N = 166), primary brain tumor (N = 197) and chronic obstructive pulmonary disease (COPD, N = 204) on cognitive complaints (Cognitive Failure Questionnaire, CFQ), anxiety and depression (Hospital Anxiety and Depression Scale, HADS) and cognitive impairments using neuropsychological tests. We combined all patient groups (OSA, stroke, brain tumor and COPD) and studied potential risk factors (demographic variables, anxiety, depression and cognitive impairments) for cognitive complaints across all patient groups using regression analysis.ResultsThe prevalence of cognitive complaints was higher in OSA patients and complaints of forgetfulness and distractibility were more severe compared to stroke and primary brain tumor patients, but similar to or lower than COPD patients. Regression analysis for the combined sample of all patient groups showed that cognitive complaints were most strongly associated with symptoms of anxiety and depression.ConclusionA high rate of OSA reported clinically significant cognitive complaints, comparable to other respiratory and neurological patients. Symptoms of anxiety and depression are important risk factors for cognitive complaints in patients with various neurological and respiratory diseases. Future studies should examine the relation between anxiety, depression and cognitive complaints in patients with OSA

Health-related quality of life in adult patients with brain metastases after stereotactic radiosurgery:A systematic, narrative review

Purpose A growing number of patients with brain metastases (BM) are being treated with stereotactic radiosurgery (SRS), and the importance of evaluating the impact of SRS on the health-related quality of life (HRQoL) in these patients has been increasingly acknowledged. This systematic review summarizes the current knowledge about the HRQoL of patients with BM after SRS. Methods We searched EMBASE, Medline Ovid, Web-of-Science, the Cochrane Database, PsycINFO Ovid, and Google Scholar up to November 15, 2018. Studies in patients with BM in which HRQoL was assessed before and after SRS and analyzed over time were included. Studies including populations of several types of brain cancer and/or several types of treatments were included if the results for patients with BM and treatment with SRS alone were described separately. Results Out of 3638 published articles, 9 studies met the eligibility criteria and were included. In 4 out of 7 studies on group results, overall HRQoL of patients with BM remained stable after SRS. In small study samples of longer-term survivors, overall HRQoL remained stable up to 12 months post-SRS. Contradictory results were reported for physical and general/global HRQoL, which might be explained by the different questionnaires that were used. Conclusions In general, SRS does not have significant negative effects on patients’ overall HRQoL over time. Future research is needed to analyze different aspects of HRQoL, differences in individual changes in HRQoL after SRS, and factors that influence these changes. These studies should take into account several methodological issues as discussed in this review

Feasibility of a home-based exercise intervention with remote guidance for patients with stable grade II and III gliomas:A pilot randomized controlled trial

Objective: In this pilot study, we investigated the feasibility of a home-based, remotely guided exercise intervention for patients with gliomas. Design: Pilot randomized controlled trial (RCT) with randomization (2:1) to exercise or control group. Subjects: Patients with stable grade II and III gliomas. Intervention: The six-month intervention included three home-based exercise sessions per week at 60%–85% of maximum heart rate. Participants wore heart rate monitors connected to an online platform to record activities that were monitored weekly by the physiotherapist. Main measures: Accrual, attrition, adherence, safety, satisfaction, patient-reported physical activity, VO2 peak (by maximal cardiopulmonary exercise testing) and body mass index (BMI) at baseline and at six-month follow-up. Results: In all, 34 of 136 eligible patients (25%) were randomized to exercise training (N = 23) or the control group (N = 11), of whom 19 and 9, respectively, underwent follow-up. Mean adherence to prescribed sessions was 79%. Patients’ experiences were positive. There were no adverse events. Compared to the control group, the exercise group showed larger improvements in absolute VO2 peak (+158.9 mL/min; 95% CI: −44.8 to 362.5) and BMI (−0.3 kg/m²; 95% CI: −0.9 to 0.2). The median increase in physical activity was 1489 metabolic equivalent of task (MET) minutes higher in the exercise group. The most reported reasons for non-participation were lack of motivation or time. Conclusion: This innovative and intensive home-based exercise intervention was feasible in a small subset of patients with stable gliomas who were interested in exercising. The observed effects suggest that the programme may improve cardiorespiratory fitness. These results support the need for large-scale trials of exercise interventions in brain tumour patients. Keywords: Glioma, brain tumour, exercise, physical training, physical fitnes

Multidimensional assessment of fatigue in patients with brain metastases before and after Gamma Knife radiosurgery

Purpose  Fatigue is a common and distressing symptom in cancer patients which negatively affects patients' daily functioning and health-related quality of life. The aim of this study was to assess multidimensional fatigue in patients with brain metastases (BM) before, and after Gamma Knife radiosurgery (GKRS).  Methods  Patients with BM, an expected survival > 3 months, and a Karnofsky Performance Status >= 70 and 104 Dutch non-cancer controls were recruited. The Multidimensional Fatigue Inventory (MFI), measuring general fatigue, physical fatigue, mental fatigue, reduced activity and reduced motivation, was used. Baseline levels of fatigue between patients and controls were compared using independent-samples t-tests. The course of fatigue over time, and clinical and psychological predictors thereof, were analyzed using linear mixed models (within-group analyses).  Results  Ninety-two, 67 and 53 patients completed the MFI at baseline, and 3 and 6 months after GKRS. Before GKRS, patients with BM experienced significantly higher levels of fatigue on all subscales compared to controls (medium to large effect sizes). Over 6 months, general and physical fatigue increased significantly (p = .009 and p <.001), and levels of mental fatigue decreased significantly (p = .027). No significant predictors of the course of fatigue over time could be identified.  Conclusions  Fatigue is a major problem for patients with BM. Different patterns over time were observed for the various aspects of fatigue in patients with BM. Information on the various aspects of fatigue is important because fatigue may negatively affect patients' functional independence, health-related quality of life, and adherence to therapy

Cognitive effects of stereotactic radiosurgery in adult patients with brain metastases:A systematic review

Purpose:  Stereotactic radiation surgery (SRS) is increasingly applied in patients with brain metastases (BM) and is expected to have fewer adverse effects on cognitive functioning than whole brain radiation therapy (WBRT). Patients with BM are often confronted with a relatively short life expectancy, and the prevention or delay of cognitive decline to maintain quality of life is a clinically and highly relevant treatment goal. This review systematically and specifically evaluates the current literature on the cognitive effects of SRS in patients with BM. Methods and materials:  Published trials on SRS alone or in combination with WBRT, including objective assessment of cognitive functioning, were identified through a systematic search of the PubMed database up to March 2018. Results:  Of the 241 records screened, 14 studies matched the selection criteria: 2 pilot studies, 7 single-group/observational trials (1 study update), and 5 randomized trials (1 secondary analysis). Conclusions:  In general, the results show little to no objective cognitive decline up to 4 months after SRS compared with WBRT. However, most trials suffered from methodologic limitations that hindered reliable conclusions. Most importantly, few studies investigated the specific cognitive effects of SRS alone or versus WBRT. Furthermore, disentangling the cognitive effects of SRS from the effects of the disease itself and from the effects of other treatments remains very difficult. By presenting this comprehensive review, we aim to encourage researchers to probe deeper into this area and to do so in a standardized and methodologically optimal manner. The ultimate objective of this line of research is to inform both doctors and patients more precisely about the cognitive effects they can expect from treatment. This study is expected to improve the quality of decision-making and maximize clinical outcomes for each individual patient

Subjective cognitive functioning in patients with a meningioma:Its course and association with objective cognitive functioning and psychological symptoms

Objective: Although meningioma patients show deficits in objective cognitive functioning (OCF) measured with neuropsychological tests, subjective cognitive functioning (SCF) has received little attention. We investigate SCF from pre- to post-surgery and its associations with OCF, psychological, sociodemographic, and clinical characteristics.Methods: SCF was measured using the Cognitive Failures Questionnaire (CFQ) one day before (T0), and three (T3) and twelve months (T12) after surgery. Patients' scores were compared to normative data and changes over time were assessed. The neuropsychological battery CNS Vital Signs and the Hospital Anxiety and Depression Scale were administered. Correlations of SCF with OCF, psychological, sociodemographic, and clinical characteristics were explored.Results: Patients reported significantly better SCF as compared with controls at T0 (N=54) and T3 (N=242), but not at T12 (N=50). A significant decrease in group level SCF was observed from T0 to T12 (n=24, p&lt;.001). SCF was associated with anxiety at all time points (rs=-0.543 to -0.352) and with depression at T3 and T12 (r=-0.338 and -0.574), but not with OCF, sociodemographic, or clinical characteristics (rs=-0.202 to 0.288).Conclusions: Meningioma patients experienced better SCF as compared to controls before and three months after surgery, which might be the result of phenomena related to disease and recovery. As the findings suggest that cognitive symptoms might increase later on, future studies should further investigate the course of SCF in meningioma patients. In clinical practice, measurements of SCF should be combined with those of OCF and psychological distress in order to determine whether and which interventions are needed.</p