Healthcare utilization and productivity loss in glioma patients and family caregivers: the impact of treatable psychological symptoms.

BACKGROUND: Gliomas are associated with significant healthcare burden, yet reports of costs are scarce. While many costs are unavoidable there may be treatable symptoms contributing to higher costs. We describe healthcare and societal costs in glioma patients at high risk for depression and their family caregivers, and explore relationships between costs and treatable symptoms. METHODS: Data from a multicenter randomized trial on effects of internet-based therapy for depressive symptoms were used (NTR3223). Costs of self-reported healthcare utilization, medication use, and productivity loss were calculated for patients and caregivers separately. We used generalized linear regression models to predict costs with depressive symptoms, fatigue, cognitive complaints, tumor grade (low-/high-grade), disease status (stable or active/progression), and intervention (use/non-use) as predictors. RESULTS: Multiple assessments from baseline through 12 months from 91 glioma patients and 46 caregivers were used. Mean overall costs per year were M = €20,587.53 (sd = €30,910.53) for patients and M = €5,581.49 (sd = €13,102.82) for caregivers. In patients, higher healthcare utilization costs were associated with more depressive symptoms; higher medication costs were associated with active/progressive disease. In caregivers, higher overall costs were linked with increased caregiver fatigue, cognitive complaints, and lower patient tumor grade. Higher healthcare utilization costs were related to more cognitive complaints and lower tumor grade. More productivity loss costs were associated with increased fatigue (all P < 0.05). CONCLUSIONS: There are substantial healthcare and societal costs for glioma patients and caregivers. Associations between costs and treatable psychological symptoms indicate that possibly, adequate support could decrease costs. TRIAL REGISTRATION: Netherlands Trial Register NTR3223.

The association between preoperative edema and postoperative cognitive functioning and health-related quality of life in WHO grade I meningioma patients.

BACKGROUND: Studies on the associations between preoperative cerebral edema, cognitive functioning, and health-related quality of life (HRQOL) in WHO grade I meningioma patients are virtually lacking. We studied the association between preoperative cerebral edema on postoperative cognitive functioning and HRQOL 6 months postoperatively in WHO grade I meningioma patients. METHODS: Twenty-one consecutive WHO grade I meningioma patients, who underwent surgery, were matched individually for age, gender, and educational level to healthy controls. Tumor and edema volume were assessed on preoperative T1- and T2-weighted MRI images, respectively. At least 5 months postoperatively, functional status, cognitive functioning, and HRQOL, using a cognitive test battery and the Short-Form Health Survey (SF-36), were determined. The correlation between preoperative tumor and cerebral edema volume with postoperative cognitive functioning and HRQOL was investigated using Kendall's tau coefficients. RESULTS: Compared to healthy controls, patients had lower verbal memory capacity (p = .012), whereas HRQOL was similar to matched healthy controls. In all cognitive domains, postoperative functioning was much lower in patients with preoperative cerebral edema than in those without. There were significant correlations between preoperative cerebral edema and tumor volume and postoperative cognitive functioning. Preoperative cerebral edema and/or tumor volume were not associated with HRQOL. CONCLUSIONS: Our results suggest that WHO grade I meningioma patients with larger volumes of preoperative cerebral edema are more at risk of experiencing limitations in longer-term cognitive functioning than patients with no or less edema preoperatively. This is an important knowledge for neurologists and neurosurgeons treating patients with a meningioma. More studies regarding the effect of peritumoral edema on cognitive functioning in meningioma patients are necessary.

Cognitive functioning and functional brain networks in postoperative WHO grade I meningioma patients.

INTRODUCTION: Meningioma patients often have subtle cognitive deficits that might be attributed to the tumor itself, to surgical treatment, or to the occurrence of seizures and their treatment. Magnetoencephalography (MEG) analysis of resting-state functional networks (RSNs) could help to understand the neurophysiological basis of cognitive impairment in these patients. We explored the correlation between RSN functional connectivity and topology of functional networks on the one hand, and cognition on the other hand in WHO grade I meningioma patients. METHODS: Twenty adult WHO grade I meningioma patients who had undergone tumor resection, as well as 20 healthy matched controls, were included. Neuropsychological assessment was done through a standardized test battery. MEG data were recorded, and projected to the anatomical space of the Automated Anatomical Labeling atlas. Functional connectivity (PLI), within the default mode network (DMN) and the bilateral frontoparietal networks were correlated to cognitive performance. Minimum spanning tree (MST) characteristics were correlated with cognitive functioning. RESULTS: Compared to healthy controls, meningioma patients had lower working memory capacity (p = 0.037). Within the patient group, lower working memory performance was associated with lower DMN connectivity and a lower maximum MST degree in the theta band (resp. p = 0.044 and p = 0.003). CONCLUSIONS: This study shows that cognitive functioning is correlated with functional connectivity in the default mode network and hub-pathology in WHO grade I meningioma patients. Future longitudinal studies are needed to corroborate these findings and to further investigate the pathophysiology of cognitive deficits and possible changes in functional brain networks in meningioma patients.

Internet-based guided self-help for glioma patients with depressive symptoms: a randomized controlled trial.

Depressive symptoms are common in glioma patients, and can negatively affect health-related quality of life (HRQOL). We performed a nation-wide randomized controlled trial to evaluate the effects of an online guided self-help intervention for depressive symptoms in adult glioma patients. Glioma patients with depressive symptoms were randomized to a 5-week online course based on problem-solving therapy, or a waiting list control group. After having received the intervention, the glioma patient groups combined were compared with patients with cancer outside the central nervous system (non-CNS cancer controls), who also received the intervention. Sample size calculations yielded 63 participants to be recruited per arm. The primary outcome [depressive symptoms (CES-D)] and secondary outcomes [fatigue (Checklist Individual Strength (CIS)) and HRQOL (Short Form-36)], were assessed online at baseline, post-intervention, and 3 and 12 months follow-up. In total, 89 glioma patients (intervention N = 45; waiting list N = 44) and 26 non-CNS cancer controls were included, of whom 35 and 54% completed the intervention, respectively. Recruitment could not be extended beyond 3.5 years due to funding. On depression, no statistically significant differences between the groups were found. Fatigue decreased post-treatment in the glioma intervention group compared with the waiting list group (p = 0.054, d = 0.306). At 12 months, the physical component summary (HRQOL) remained stable in glioma patients, while scores improved in non-CNS cancer controls (p = 0.035, d = 0.883). In this underpowered study, no evidence for the effectiveness of online guided self-help for depression or HRQOL in glioma patients was found, but it may improve fatigue. Trial registration Netherlands Trial Register NTR3223.

Evaluation of the psychometric properties of the EORTC chemotherapy-induced peripheral neuropathy questionnaire (QLQ-CIPN20).

PURPOSE: To investigate the scale structure and psychometrics of the EORTC chemotherapy-induced peripheral neuropathy module (QLQ-CIPN20). METHODS: Using confirmatory factor analyses (CFA), we tested two hypothesized scale structure models of the QLQ-CIPN20 in 473 patients with non-small cell lung cancer, 281 patients with heterogeneous cancer diagnoses, and 500 patients with colorectal cancer. We also modeled the two hypothesized models as bi-factor models. These included a general factor, in addition to the specific domain factors. Additional models were investigated with exploratory factor analysis (EFA). Known groups validity was evaluated where justified. RESULTS: CFA could not confirm the two hypothesized models (Model 1: CFI < 0.926; TLI < 0.914; RMSEA > 0.077 and Model 2: CFI < 0.906; TLI < 0.887; RMSEA > 0.105) in any of the three samples. Including a general factor to these two hypothesized models to produce a bi-factor model also did not yield satisfactory results. Using EFA, we identified four different factor structures in the three samples that were unstable due to cross loadings of the items. When scoring the QLQ-CIPN20 as a simple, additive checklist evidence was found for known groups validity in the first two samples based on Common Toxicity Criteria (CTC-AE), and in the third sample based on exposure to CIPN-inducing chemotherapy. CONCLUSIONS: Neither CFA nor EFA yielded support for a stable subscale structure for the QLQ-CIPN20. Scoring the questionnaire as a simple additive checklist results in acceptable validity.

Impact of neurocognitive deficits on patient-proxy agreement regarding health-related quality of life in low-grade glioma patients.

PURPOSE: Clinical trials in glioma patients with neurocognitive deficits face challenges due to lacking or unreliable patient self-reports on their health-related quality of life (HRQOL). Patient-proxy data could help solve this issue. We determined whether patient-proxy concordance levels were affected by patients' neurocognitive functioning. METHODS: Patient and patient-by-proxy HRQOL ratings were assessed via SF-36 and EORTC QLQ-BN20, respectively, in 246 patients. Data on neurocognitive functioning were collected on a subgroup of 195 patients. Patient-proxy agreement was measured using the Bland-Altman limit of agreement, the mean difference, the concordance correlation coefficient (CCC), and the percentage difference (PD, ±0, 5, or 10 points). We defined patients to be cognitively impaired (n = 66) or cognitively intact (n = 129) based on their neurocognitive performance. RESULTS: Patients rated their physical function and general health to be better than their proxies did, while at the same time, patients reported more visual disorders, communication deficits, itchy skin, and problems with bladder control. The cognitively impaired subgroup reported poorer physical functioning, more visual disorders, headaches, itchy skin, and issues with bladder control. In the cognitively intact group, no statistical significant differences were observed between patients and proxies. Not surprisingly, Bland-Altman plots revealed a high agreement between the patient and patient-by-proxy rating in all HRQOL domains ranging from 95 to 99 %. The CCC was fairly high in all HRQOL domains (0.37-0.80), and the percentage of perfect agreement (PD ± 0) ranged from 8.5 to 76.8 %. In the cognitively impaired patients, the mean difference between patients and proxies was overall larger, and accordingly, agreement based on Bland-Altman plots was lower. CONCLUSIONS: The level of agreement between patient and patient-by-proxy ratings of low-grade glioma patients' HRQOL is generally high. However, patient-proxy agreement is lower in patients with neurocognitive deficits than in patients without neurocognitive deficits.

Seizure reduction is a prognostic marker in low-grade glioma patients treated with temozolomide.

We aimed to analyze the value of seizure reduction and radiological response as prognostic markers of survival in patients with low-grade glioma (LGG) treated with temozolomide (TMZ) chemotherapy. We retrospectively reviewed adult patients with a progressive LGG and uncontrolled epilepsy in two hospitals (VUmc Amsterdam; MCH The Hague), who received chemotherapy with TMZ between 2002 and 2014. End points were a ≥50 % seizure reduction and MRI response 6, 12 and 18 months (mo) after the start of TMZ, and their relation with progression-free survival (PFS) and overall survival (OS). We identified 53 patients who met the inclusion criteria. Seizure reduction was an independent prognostic factor for both PFS (HR 0.38; 95 % CI 0.19-0.73; p = 0.004) and OS (HR 0.39; 95 % CI 0.18-0.85; p = 0.018) after 6mo, adjusting for age and histopathological diagnosis, as well as after 12 and 18mo. Patients with an objective radiological response showed a better OS (median 87.5mo; 95 % CI 62.0-112.9) than patients without a response (median 34.4mo; 95 % CI 26.1-42.6; p = 0.046) after 12mo. However, after 6 and 18mo OS was similar in patients with and without a response on MRI. Seizure reduction is an early and consistent prognostic marker for survival after treatment with TMZ, that seems to precede the radiological response. Therefore, seizure reduction may serve as a surrogate marker for tumor response.

Antiepileptic drug treatment in the end-of-life phase of glioma patients: a feasibility study.

BACKGROUND: During the end-of-life (EOL) phase of glioma patients, a rapid deterioration in neurological functioning may interfere with the oral intake of antiepileptic drugs (AEDs). We aimed to assess the feasibility of non-oral AED treatment in an out-of-hospital setting according to an expert-based guideline. METHODS: Glioma patients with a history of epilepsy, in whom further antitumor therapy was considered to be no longer meaningful, were recruited at two Dutch hospitals. As soon as swallowing difficulties developed, the patient's caregiver administered prophylactic treatment with buccal clonazepam. Acute seizures were treated with intranasal midazolam. We evaluated the adherence to the study medication, seizure prevalence, and caregiver's satisfaction. RESULTS: Of the 34 patients who were approached, 25 gave consent to participate and 23 had died at the end of the study. Thirteen of 19 patients (68.4 %) who had developed swallowing difficulties showed adherence to the study protocol. Thirteen patients used prophylactic buccal clonazepam, of which eight patients remained seizure-free until death. Six patients received treatment with intranasal midazolam at least once. In all patients, seizure control was reached. None of the patients needed to be transferred to the hospital due to recurrent seizures. All caregivers were to some degree satisfied with the use of the study medication. CONCLUSIONS: Our results demonstrate that it is feasible to treat seizures with a combination of non-oral benzodiazepines in the EOL phase of glioma patients, as it seems to provide an important level of comfort among caregivers to be able to manage seizures at home.

Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment.

Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O (6) -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-naïve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.

Seizure reduction in a low-grade glioma: more than a beneficial side effect of temozolomide.

BACKGROUND: Seizures are a common symptom in patients with low-grade glioma (LGG), negatively influencing quality of life, if uncontrolled. Besides antiepileptic drugs, antitumour treatment might contribute to a reduction in seizure frequency. The aim of this study was to determine the effect of temozolomide (TMZ) chemotherapy on seizure frequency, to identify factors associated with post-treatment seizure reduction and to analyse the prognostic value of seizure reduction for survival. METHODS: We retrospectively reviewed adult patients with supratentorial LGG and epilepsy who received chemotherapy with TMZ as initial treatment or for progressive disease in two hospitals (VUmc Amsterdam; MCH The Hague) between 2002 and 2012. RESULTS: We identified 104 patients with LGG with epilepsy who had received TMZ. Uncontrolled epilepsy in the 3 months preceding chemotherapy was present in 66 of 104 (63.5%) patients. A ≥ 50% reduction in seizure frequency after 6 months occurred in 29 of 66 (43.9%) patients. Focal symptoms at presentation (OR 6.55; 95% CI 1.45 to 32.77; p = 0.015) appeared to be positively associated with seizure reduction. Seizure reduction was an independent prognostic factor for progression-free survival (HR 0.32; 95% CI 0.15 to 0.66; p = 0.002) and overall survival (HR 0.33; 95% CI 0.14 to 0.79; p = 0.013), along with a histological diagnosis of oligodendroglioma (HR 0.38; 95% CI 0.17 to 0.86; p = 0.021). Objective responses on MRI were similar for patients with and without seizure reduction. CONCLUSIONS: TMZ may contribute to an important reduction in seizure frequency in patients with LGG. Seizure reduction following TMZ treatment has prognostic significance and may serve as an important clinical outcome measure in patients with LGG.

Epilepsy surgery outcome and functional network alterations in longitudinal MEG: a minimum spanning tree analysis.

Seizure freedom after resective epilepsy surgery is not obtained in a substantial number of patients with medically intractable epilepsy. Functional neural network analysis is a promising technique for more accurate identification of the target areas for epilepsy surgery, but a better understanding of the correlations between changes in functional network organization due to surgery and postoperative seizure status is required. We explored these correlations in longitudinal magnetoencephalography (MEG) recordings of 20 lesional epilepsy patients. Resting-state MEG recordings were obtained at baseline (preoperatively; T0) and at 3-7 (T1) and 9-15months after resection (T2). We assessed frequency-specific functional connectivity and performed a minimum spanning tree (MST) network analysis. The MST captures the most important connections in the network. We found a significant positive correlation between functional connectivity in the lower alpha band and seizure frequency at T0, especially in regions where lesions were located. MST leaf fraction, a measure of integration of information in the network, was significantly increased between T0 and T2, only for the seizure-free patients. This is in line with previous work, which showed that lower functional network integration in lesional epilepsy patients is related to higher epilepsy burden. Finally, eccentricity and betweenness centrality, which are measures of hub-status, decreased between T0 and T2 in seizure free patients, also in regions that were anatomically close to resection cavities. Our results increase insight into functional network changes in successful epilepsy surgery and might eventually be utilized for optimization of neurosurgical approaches.

Measuring health-related quality of life in high-grade glioma patients at the end of life using a proxy-reported retrospective questionnaire.

To develop, validate, and report on the use of a retrospective proxy-reported questionnaire measuring health-related quality of life (HRQoL) in the end-of-life (EOL) phase of high-grade glioma (HGG) patients. Items relevant for the defined construct were selected using existing questionnaires, topics identified as important in literature, and expert opinion (experienced neuro-oncologists and EOL experts). Psychometric properties, content validity and internal consistency, were determined and the questionnaire was subsequently adapted. Proxy-reported HRQoL data of HGG patients in the EOL, including changes over time, were analyzed. Twenty-nine items were selected covering seven domains; physical comfort, physical and cognitive functioning, psychological, social and spiritual well-being, and overall quality of life. Relatives of 83 deceased HGG patients completed the questionnaire. Content validity was assessed to be adequate. Internal consistency in the domains varied from reasonable to good. Two items were excluded due to poor psychometric properties. Symptom burden increased (p < 0.01), except for nausea (p = 0.058), as death approached. Cognitive, physical and psychological functioning deteriorated over time (all p < 0.01). Acceptance of disease seemed to increase slightly towards death, but this was not significant (p = 0.058). Participating in social activities and family life was rated as poor (≤ 50), whereas received support from their social environment and dying with dignity were rated as good (>50). Overall quality of life was rated as poor, mean (SD) of 29 (26). Measuring HRQoL at the EOL of HGG patients with a retrospective, proxy-reported questionnaire was feasible, yielding a validated instrument. HRQoL was reported as poor and deteriorated as death approached.

Internet-based guided self-help for glioma patients with depressive symptoms: design of a randomized controlled trial.

BACKGROUND: Among glioma patients, depression is estimated to be more prevalent than in both the general population and the cancer patient population. This can have negative consequences for both patients and their primary informal caregivers (e.g., a spouse, family member or close friend). At present, there is no evidence from randomized controlled trials for the effectiveness of psychological treatment for depression in glioma patients. Furthermore, the possibility of delivering mental health care through the internet has not yet been explored in this population. Therefore, a randomized controlled trial is warranted to evaluate the effects of an internet-based, guided self-help intervention for depressive symptoms in glioma patients. METHODS/DESIGN: The intervention is based on problem-solving therapy. An existing 5-week course is adapted for use by adult glioma patients with mild to moderate depressive symptoms (Center for Epidemiology Studies Depression Scale score ≥12). Sample size calculations yield 126 glioma patients to be included, who are randomly assigned to either the intervention group or a waiting list control group. In addition, we aim to include 63 patients with haematological cancer in a non-central nervous system malignancy control group. Assessments take place at baseline, after 6 and 12 weeks, and after 6 and 12 months. Primary outcome measure is the change in depressive symptoms. Secondary outcome measures include health-related quality of life, fatigue, costs and patient satisfaction. In addition, all patients are asked to assign a primary informal caregiver, who does not participate in the intervention but who is asked to complete similar assessments. Their mood, health-related quality of life and fatigue is evaluated as well. DISCUSSION: This is the first study to evaluate the effects of problem-solving therapy delivered through the internet as treatment for depressive symptoms in glioma patients. If proven effective, this treatment will contribute to the mental health care of glioma patients in clinical practice. TRIAL REGISTRATION: Netherlands Trial Register NTR3223.

Withdrawal of antiepileptic drugs in glioma patients after long-term seizure freedom: design of a prospective observational study.

BACKGROUND: Epilepsy is common in patients with a glioma. Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment, but may cause side effects and may negatively impact neurocognitive functioning and quality of life. Besides antiepileptic drugs, anti-tumour treatment, which currently consists of surgery, radiotherapy and/or chemotherapy, may contribute to seizure control as well. In glioma patients with seizure freedom after anti-tumour therapy the question emerges whether AEDs should be continued, particularly in the case where anti-tumour treatment has been successful. We propose to explore the possibility of AED withdrawal in glioma patients with long-term seizure freedom after anti-tumour therapy and without signs of tumour progression. METHODS/DESIGN: We initiate a prospective, observational study exploring the decision-making process on the withdrawal or continuation of AEDs in low-grade and anaplastic glioma patients with stable disease and prolonged seizure freedom after anti-tumour treatment, and the effects of AED withdrawal or continuation on seizure freedom. We recruit participants through the outpatient clinics of three tertiary referral centers for brain tumour patients in The Netherlands. The patient and the treating physician make a shared decision to either withdraw or continue AED treatment. Over a one-year period, we aim to include 100 glioma patients. We expect approximately half of the participants to be willing to withdraw AEDs. The primary outcome measures are: 1) the outcome of the shared-decision making on AED withdrawal or continuation, and decision related arguments, and 2) seizure freedom at 12 months and 24 months of follow-up. We will also evaluate seizure type and frequency in case of seizure recurrence, as well as neurological symptoms, adverse effects related to AED treatment or withdrawal, other anti-tumour treatments and tumour progression. DISCUSSION: This study addresses two issues that are currently unexplored. First, it will explore the willingness to withdraw AEDs in glioma patients, and second, it will assess the risk of seizure recurrence in case AEDs are withdrawn in this specific patient population. This study aims to contribute to a more tailored AED treatment, and prevent unnecessary and potentially harmful use of AEDs in glioma patients.

The end-of-life phase of high-grade glioma patients: a systematic review.

BACKGROUND: High-grade gliomas (HGG) are rare and incurable; yet, these neoplasms result in a disproportionate share of cancer morbidity and mortality. Treatment of HGG patients is directed not merely towards prolonging life but also towards quality of life, which becomes the major goal in the end of life (EOL). The latter has received increasing attention over the last decade. METHODS: We reviewed the literature related to the EOL phase of HGG patients from 1966 up to April 2012. Articles were retrieved from PubMed, Embase, Cinahl, PsycINFO and Cochrane database. We then selected papers for analysis using pre-determined inclusion criteria and subtracted information on the topics of interest. RESULTS: The search yielded 695 articles, of which 17 were classified eligible for analysis according to pre-defined inclusion criteria. Reviewed topics were symptoms and signs, quality of life and quality of dying, caregiver burden, organization and location of palliative care, supportive treatment, and EOL decision making. Nearly all identified studies were observational, with only two non-randomized intervention studies. Symptom burden is high in the EOL phase and affects the quality of life of both patient and carer. Palliative care services are more intensively used compared to other cancer patients. Cognitive deficits increase as the disease progresses, hampering communication and decision making. CONCLUSION: The EOL phase of HGG is substantially different from other patient groups, and more clinical studies in HGG on supportive medication, advance care planning and decision making are required. The organization of care, development of guidelines and interventions to decrease caregiver burden in the EOL phase are critical as well.

Health-related quality of life in high-grade glioma patients.

Gliomas are malignant primary brain tumors and yet incurable. Palliation and the maintenance or improvement of the patient's quality of life is therefore of main importance. For that reason, health-related quality of life (HRQoL) has become an important outcome measure in clinical trials, next to traditional outcome measures such as overall and progression-free survivals, and radiological response to treatment. HRQoL is a multidimensional concept covering physical, psychological, and social domains, as well as symptoms induced by the disease and its treatment. HRQoL is assessed by using self-reported, validated questionnaires. Various generic HRQoL questionnaires, which can be supplemented with a brain tumor- specific module, are available. Both the tumor and its treatment can have a negative effect on HRQoL. However, treatment with surgery, radiotherapy, chemotherapy, and supportive treatment may also improve patients' HRQoL, in addition to extending survival. It is expected that the impact of HRQoL measurements in both clinical trials and clinical practice will increase. Hence, it is important that HRQoL data are collected, analyzed, and interpreted correctly. Methodological issues such as selection bias and missing data may hamper the interpretation of HRQoL data and should therefore be accounted. In clinical trials, HRQoL can be used to assess the benefits of a new treatment strategy, which should be weighed carefully against the adverse effects of that treatment. In daily clinical practice, HRQoL assessments of an individual patient can be used to inform physicians about the impact of a specific treatment strategy, and it may facilitate the communication between the physicians and the patients.

The end-of-life phase of high-grade glioma patients: dying with dignity?

BACKGROUND: In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient's personal dignity. We aimed to (a) assess the proportion of HGG patients dying with dignity as perceived by their relatives and (b) identify disease and care factors correlated with dying with dignity in HGG patients. METHODS: We approached relatives of a cohort of 155 deceased HGG patients for the study. Participants completed a questionnaire concerning the EOL phase of the patient, covering several subthemes: (a) symptoms and signs, (b) health-related quality of life, (c) decision making, (d) place and quality of EOL care, and (e) dying with dignity. RESULTS: Relatives of 81 patients participated and 75% indicated that the patient died with dignity. These patients had fewer communication deficits, experienced fewer transitions between health care settings in the EOL phase, and more frequently died at their preferred place of death. Relatives were more satisfied with the physician providing EOL care and reported that the physician adequately explained treatment options. Multivariate analysis identified satisfaction with the physician, the ability to communicate, and the absence of transitions between settings as most predictive of a dignified death. CONCLUSIONS: Physicians caring for HGG patients in the EOL phase should timely focus on explaining possible treatment options, because patients experience communication deficits toward death. Physicians should strive to allow patients to die at their preferred place and avoid transitions during the last month of life.

Health-related quality of life of significant others of patients with malignant CNS versus non-CNS tumors: a comparative study.

It is often assumed that brain tumor patients' significant others (SOs: partners, other family members or close friends) may face greater stress than those of patients with malignancies not involving the central nervous system (CNS), due to progressive changes in neurological and cognitive functioning. We compared health-related quality of life (HRQOL) of SOs of patients with high-grade glioma (HGG) and low-grade glioma (LGG) with that of SOs of patients with non-CNS tumors with similar prognosis and at a similar phase in the disease trajectory (i.e. non-small cell lung cancer (NSCLC) and low-grade hematological malignancies (NHL/CLL), respectively). HRQOL of SOs and patients was assessed using the Short Form-36 (SF-36) Health Survey. Patients' neurological functioning was indexed and they underwent comprehensive neurocognitive testing. SOs of 213 LGG patients, 99 NHL/CLL patients, 55 HGG patients and 29 NSCLC patients participated. The SOs of LGG and NHL/CLL patients reported similar levels of HRQOL. SOs of HGG patients reported significantly lower mental health scores (MCS; p = 0.041) and social functioning (p = 0.028) than those of NSCLC patients. Mental health scores (MCS) of HGG and NSCLC patients were associated significantly with the mental health of their SOs (p = 0.013 and p < 0.001, respectively). Surprisingly, HGG patients' cognitive and neurological functioning were not predictive of SOs' mental health at the multivariate level. SOs of patients with highly malignant CNS tumors in the acute phase are at increased risk of compromised HRQOL compared to those of patients with systemic tumors without CNS involvement and a comparable life expectancy.

Enhancing quality of life and mastery of informal caregivers of high-grade glioma patients: a randomized controlled trial.

High-grade gliomas (HGG) are serious primary brain tumors that may prevent the patient from functioning normally in social, emotional and cognitive respect. Often the partner's role will convert to that of informal caregiver. Consequently, they may experience significant stress and reductions in caregiver mastery, negatively affecting their health-related quality of life (HRQOL). We aimed at (1) determining factors that impact HRQOL and mastery of caregivers of HGG patients, and (2) investigate if a structured intervention consisting of psychoeducation and cognitive behavioral therapy leads to improvements in the mental component of HRQOL and mastery of caregivers. Fifty-six patient-caregiver dyads were randomly assigned to the intervention group or the care as usual group. The intervention program consisted of six one-hour sessions with a psychologist. Participants completed questionnaires concerning their perceptions of the patients' HRQOL (SF-36), neurological functioning (BN20), and cognitive functioning (MOS), and concerning their own HRQOL (SF-36) and feelings of caregiver mastery (CMS) both at baseline (i.e. before randomization) and every 2 months thereafter until 8 months later, five times in total. Patients' HRQOL and neurological functioning were found to be related to HRQOL and feelings of mastery of the informal caregiver at baseline. The intervention helped caregivers in maintaining a stable level of HRQOL and improved feelings of mastery over an 8 month period. Our findings suggest that informal caregivers can benefit from a psychological intervention as it is a helpful tool in maintaining a stable level of mental functioning and caregiver mastery.

Epilepsy in patients with a brain tumour: focal epilepsy requires focused treatment.

Brain tumours frequently cause epileptic seizures. Medical antiepileptic treatment is often met with limited success. Pharmacoresistance, drug interactions and adverse events are common problems during treatment with antiepileptic drugs. The unpredictability of epileptic seizures and the treatment-related problems deeply affect the quality of life of patients with a brain tumour. In this review, we focus on both clinical and basic aspects of possible mechanisms in epileptogenesis in patients with a brain tumour. We provide an overview of the factors that are involved in epileptogenesis, starting focally at the tumour and the peritumoral tissue and eventually extending to alterations in functional connectivity throughout the brain. We correlate this knowledge to the known mechanisms of antiepileptic drugs. We conclude that the underlying mechanisms of epileptogenesis in patients with a brain tumour are poorly understood. The currently available antiepileptic drugs have little to no influence on the known epileptogenic mechanisms that could contribute to the poor efficacy. Better understanding of focal changes that are involved in epileptogenesis may provide new tools for optimal treatment of both the seizures and the underlying tumour. In our opinion, therapy for every patient with a brain tumour suffering from epilepsy should first and foremost aim at eliminating the tumour as well as the epileptic focus through resection combined with postoperative treatment, and only if this strategy does not result in adequate seizure control should medical antiepileptic treatment be intensified. If this strategy, however, results in sustained seizure freedom, tapering of antiepileptic drugs should be considered in the long term.