Background This study aimed at investigating antiepileptic drug (AED) prescription preferences in patients with brain tumor-related epilepsy (BTRE) among the European neuro-oncology community, the... Show moreBackground This study aimed at investigating antiepileptic drug (AED) prescription preferences in patients with brain tumor-related epilepsy (BTRE) among the European neuro-oncology community, the considerations that play a role when initiating AED treatment, the organization of care, and practices with regard to AED withdrawal. Methods A digital survey containing 31 questions about prescription preferences of AEDs was set out among members of the European Association of Neuro-Oncology (EANO). Results A total of 198 respondents treating patients with BTRE participated of whom 179 completed the entire survey. Levetiracetam was the first choice in patients with BTRE for almost all respondents (90% [162/181]). Levetiracetam was considered the most effective AED in reducing seizure frequency (72% [131/181]) and having the least adverse effects (48% [87/181]). Common alternatives for levetiracetam as equivalent first choice included lacosamide (33% [59/181]), lamotrigine (22% [40/181]), and valproic acid (21% [38/181]). Most crucial factors to choose a specific AED were potential adverse effects (82% [148/181]) and interactions with antitumor treatments (76% [137/181]). In the majority of patients, neuro-oncologists were involved in the treatment of seizures (73% [132/181])). Other relevant findings were that a minority of respondents ever prescribe AEDs in brain tumor patients without epilepsy solely as prophylaxis (29% [53/181]), but a majority routinely considers complete AED withdrawal in BTRE patients who are seizure-free after antitumor treatment (79% [141/179]). Conclusions Our results show that among European professionals treating patients with BTRE levetiracetam is considered the first choice AED, with the presumed highest efficacy and least adverse effects. Show less
Background: Glioma patients may experience behavioral and personality changes (BPC), negatively impacting their lives and that of their relatives. However, there is no clear definition of BPC for... Show moreBackground: Glioma patients may experience behavioral and personality changes (BPC), negatively impacting their lives and that of their relatives. However, there is no clear definition of BPC for adult glioma patients, and here we aimed to determine which characteristics of BPC are relevant to include in this definition.Methods: Possible characteristics of BPC were identified in the literature and presented to patients and (former) caregivers in an online survey launched via the International Brain Tumour Alliance. Participants had to rate the relevance of each presented characteristic of BPC, the three characteristics with the most impact on their lives, and possible missing characteristics. A cluster analysis and discussions with experts provided input to categorize characteristics and propose a definition for BPC.Results: Completed surveys were obtained from 140 respondents; 35% patients, 50% caregivers, and 15% unknown. Of 49 proposed characteristics, 35 were reported as relevant by at least 25% (range: 7%-44%) of respondents. Patients and caregivers rated different characteristics as most important. Common characteristics included in the top 10 of both patients and caregivers were lack of motivation, change in being socially active, not able to finish things, and change in the level of irritation. No characteristics were reported missing by >= 5 respondents. Three categories of BPC were identified: (1) emotions, needs, and impulses (2) personality traits, and (3) poor judgement abilities.Conclusion: The work resulted in a proposed definition for BPC in glioma patients, for which endorsement from the neuro-oncological community will be sought. A next step is to identify or develop an instrument to evaluate BPC in glioma patients. Show less
Glioblastoma (GB) is the most common and most malignant primary brain tumour in adults. Despite much effort, gold standard therapy has not changed since the introduction of adjuvant temozolomide in... Show moreGlioblastoma (GB) is the most common and most malignant primary brain tumour in adults. Despite much effort, gold standard therapy has not changed since the introduction of adjuvant temozolomide in 2005 and prognosis remains poor. Despite this, there has been significant improvement in the surgical technology and technique, that has allowed for increased rates of safe maximal resection of the tumour. In addition, our increased knowledge of the biology of GB has revealed more potential targets, especially in the field of immunotherapy, which has been successful in revolutionising treatment of other cancers. We review the current best practice for the treatment of GB and explore some of the more recent advances in GB management from both a surgical and molecular therapeutic perspective. Show less
Background: Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic review, we... Show moreBackground: Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic review, we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma.Methods: Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched up to June 2020. Three different outcomes for both mono- and polytherapy were extracted from all eligible articles: (i) seizure freedom; (ii) >= 50% reduction in seizure frequency; and (iii) treatment failure. Weighted averages (WA) were calculated for outcomes at 6 and 12 months.Results: A total of 66 studies were included. Regarding the individual outcomes on the efficacy of monotherapy, the highest seizure freedom rate at 6 months was with phenytoin (WA = 72%) while at 12-month pregabalin (WA = 75%) and levetiracetam (WA = 74%) showed highest efficacy. Concerning >= 50% seizure reduction rates, levetiracetam showed highest efficacy at 6 and 12 months (WAs of 82% and 97%, respectively). However, treatment failure rates at 12 months were highest for phenytoin (WA = 34%) and pregabalin (41%). When comparing the described polytherapy combinations with follow-up of >= 6 months, levetiracetam combined with phenytoin was most effective followed by levetiracetam combined with valproic acid.Conclusion: Given the heterogeneous patient populations and the low scientific quality across the different studies, seizure rates need to be interpreted with caution. Based on the current limited evidence, with the ranking of AEDs being confined to the AEDs studied, levetiracetam, phenytoin, and pregabalin seem to be most effective as AED monotherapy in glioma patients with epilepsy, with levetiracetam showing the lowest treatment failure rate, compared to the other AEDs studied. Show less
Linden, S.D. van der; Rutten, G.J.M.; Dirven, L.; Taphoorn, M.J.B.; Satoer, D.D.; Dirven, C.M.F.; ... ; Gehring, K. 2021
Background Evidence-based cognitive rehabilitation programs for brain tumor patients are not widely available, despite the high need. We aimed to evaluate the effects of a tablet-based cognitive... Show moreBackground Evidence-based cognitive rehabilitation programs for brain tumor patients are not widely available, despite the high need. We aimed to evaluate the effects of a tablet-based cognitive rehabilitation program on cognitive performance, cognitive complaints, fatigue, and psychological distress in primary brain tumor patients following neurosurgery. Also, attrition, adherence and patient satisfaction with the program were evaluated. Methods Adults with presumed low-grade glioma and meningioma were recruited before surgery. Three months thereafter, participants were allocated to the intervention group or waiting-list control group using minimization. The 10-week eHealth app ReMind, based on the effective face-to-face intervention, consisted of psychoeducation, strategy-training and attention retraining. Performance-based cognitive outcomes and patient-reported outcomes were assessed before surgery and 3, 6 and 12 months thereafter. Mean scores, percentages of cognitively impaired individuals and reliable change indices (RCIs) were compared between groups. Results Sixty-two out of 183 eligible patients were randomized. Of the people who declined, 56% reported that participation would to be too burdensome. All participants found a tablet-app suitable for delivery of cognitive rehabilitation and 90% rated the program as "good" or "excellent". Performance-based cognitive outcomes and patient-reported outcomes did not significantly differ in group means over time nor RCIs between the intervention (final n = 20) and control group (final n = 25). Conclusions Recruitment at this early stage was difficult, resulting in limited statistical power. No significant effects were demonstrated, while adherence and satisfaction with the eHealth program were good. In clinical practice, ReMind may be helpful, if timing would be adapted to patients' needs. Show less
Meulen, M. van der; Dirven, L.; Habets, E.J.J.; Bakunina, K.; Smits, M.; Achterberg, H.C.; ... ; Bromberg, J.E.C. 2021
Background. To analyze the effect of treatment on neurocognitive functioning and the association of neurocognition with radiological abnormalities in primary central nervous system lymphoma (PCNSL)... Show moreBackground. To analyze the effect of treatment on neurocognitive functioning and the association of neurocognition with radiological abnormalities in primary central nervous system lymphoma (PCNSL).Methods. One hundred and ninety-nine patients from a phase Ill trial (HOVON 105/ALLG NHL 24), randomized to standard chemotherapy with or without rituximab, followed in patients <= 60 years old by 30-Gy whole-brain radiotherapy (WBRT), were asked to participate in a neuropsychological evaluation before and during treatment, and up to 2 years posttreatment. Scores were transformed into a standardized z-score; clinically relevant changes were defined as a change in z-score of >= SD.The effect of WBRT was analyzed in irradiated patients. All M Rls were centrally assessed for white matter abnormalities and cerebral atrophy, and their relation with neurocognitive scores over time in each domain was calculated.Results. 125/199 patients consented to neurocognitive evaluation. Statistically significant improvements in neurocognition were seen in all domains. A clinically relevant improvement was seen only in the motor speed domain, without differences between the arms. In the follow-up of irradiated patients (n = 43), no change was observed in any domain score, compared to after WBRT. Small but significant inverse correlations were found between neurocognitive scores over time and changes in white matter abnormalities (regression coefficients: -0.048 to -0.347) and cerebral atrophy (-0.212 to -1.774).Conclusions. Addition of rituximab to standard treatment in PCNSL patients did not impact neurocognitive functioning up to 2 years posttreatment, nor did treatment with 30-Gy WBRT in patients <= 60 years old. Increased white matter abnormalities and brain atrophy showed weak associations with neurocognition. Show less
Opijnen, M.P. van; Meer, P.B. van der; Dirven, L.; Fiocco, M.; Kouwenhoven, M.C.M.; Bent, M.J. van den; ... ; Koekkoek, J.A.F. 2021
Purpose Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently... Show morePurpose Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide. Methods In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2-4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity. Results We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI 26-51%) versus 30% (95%CI 20-41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI 0.46-1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. Conclusion Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy. Show less
Opijnen, M.P. van; Meer, P.B. van der; Dirven, L.; Fiocco, M.; Kouwenhoven, M.C.M.; Bent, M.J. van den; ... ; Koekkoek, J.A.F. 2021
Purpose Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently... Show morePurpose Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide. Methods In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2-4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity. Results We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI 26-51%) versus 30% (95%CI 20-41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI 0.46-1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. Conclusion Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy. Show less
Background. EORTC study 22033-26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone... Show moreBackground. EORTC study 22033-26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of RT on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning.Methods. Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model, memory functioning was compared between treatment arms and over time.Results. Neuropsychological assessment was performed in 98 patients (53 RT, 46 TMZ). At 12 months, compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, sex, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (P = 0.017) and total number of words recalled (Total Recall; P < 0.001, albeit with delayed improvement in RT patients (group by time; P = 0.011). Memory functioning was not associated with RT gross, clinical, or planned target volumes.Conclusion. In patients with high-risk low-grade glioma there is no indication that in the first year after treatment, RT has a deleterious effect on memory function compared with TMZ chemotherapy. Show less
Meer, P.B. van der; Koekkoek, J.A.F.; Bent, M.J. van den; Dirven, L.; Taphoorn, M.J.B. 2021
Introduction AEDs have been associated with depression, anxiety, and cognitive impairment, all frequent complications of glioma and its subsequent treatment, with considerable morbidity and an... Show moreIntroduction AEDs have been associated with depression, anxiety, and cognitive impairment, all frequent complications of glioma and its subsequent treatment, with considerable morbidity and an adverse effect on health-related quality of life. This study aimed to determine the independent association between AED use and self-reported depression, anxiety, and subjective cognitive impairment in glioma patients. Methods In this multicenter cross-sectional study, depression and anxiety were assessed with the HADS and subjective cognitive impairment was assessed with the MOS-CFS. Univariable logistic regression analyses were performed on all potential confounding predictor variables. Potential confounders were included in the multivariable analyses if p-value < 0.1, to evaluate whether use of AEDs was independently related to depression, anxiety, and/or subjective cognitive impairment. Results A total of 272 patients were included. Prevalence of depression differed significantly between patients not using (10%) and using AEDs (21%, unadjusted Odds Ratio [uOR] = 2.29 [95%CI 1.05-4.97], p = 0.037), but after correction for confounders the statistical significant difference was no longer apparent (adjusted Odds Ratio [aOR] = 1.94 [95%CI 0.83-4.50], p = 0.125). Prevalences of anxiety (aOR = 1.17 [95%CI 0.59-2.29], p = 0.659) and subjective cognitive impairment (aOR = 0.83 [95%CI 0.34-2.04], p = 0.684) did not differ significantly before or after adjustment of confounders between patients not using (19% and 16%, respectively) and using AEDs (26% and 21%, respectively). Conclusions Our results indicate AED use was not independently associated with concurrent depression, anxiety, or subjective cognitive impairment in glioma patients. Alternative factors seem to have a greater contribution to the risk of developing neuropsychiatric symptoms in glioma patients. Show less
Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that... Show moreSomatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1(R132H) mutations. Patients harbouring IDH1(R132H) mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H IDH1/2 mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1(R132H) have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1(R132H) mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication. Show less
Meer, P.B. van der; Dirven, L.; Fiocco, M.; Vos, M.J.; Kouwenhoven, M.C.M.; Bent, M.J. van den; ... ; Koekkoek, J.A.F. 2021
Objective This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first-line monotherapy levetiracetam vs valproic acid in glioma patients with... Show moreObjective This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first-line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy.Methods In this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Maximum duration of follow-up was 36 months.Results In total, 776 patients using levetiracetam and 659 using valproic acid were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure for any reason was significantly lower for levetiracetam compared to valproic acid (12 months: 33% [95% confidence interval (CI) 29%-38%] vs 50% [95% CI 45%-55%]; P < .001). When looking at specific reasons of treatment failure, treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95% CI 12%-19%] vs 28% [95% CI 23%-32%]; P < 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95% CI 11%-18%] vs 15% [95% CI 11%-18%]; P = .636).Significance Our results suggest that levetiracetam may have favorable efficacy compared to valproic acid, whereas level of toxicity seems similar. Therefore, levetiracetam seems to be the preferred choice for first-line AED treatment in patients with glioma. Show less
Roth, P.; Pace, A.; Rhun, E. le; Weller, M.; Ay, C.; Moyal, E.C.J.; ... ; ESMO Guidelines Comm 2021
Purpose Being able to function independently in society is an important aspect of quality of life. This ability goes beyond self-care, requires higher order cognitive functioning, and is typically... Show morePurpose Being able to function independently in society is an important aspect of quality of life. This ability goes beyond self-care, requires higher order cognitive functioning, and is typically measured with instrumental activities of daily living (IADL) questionnaires. Cognitive deficits are frequently observed in brain tumour patients, however, IADL is almost never assessed because no valid and reliable IADL measure is available for this patient group. Therefore, this measure is currently being developed. Methods This international multicentre study followed European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group module development guidelines. Three out of four phases are completed: phases (I) generation of items, (II) construction of the item list, and (III) pre-testing. This paper reports the item selection procedures and preliminary psychometric properties of the questionnaire. Brain tumour patients (gliomas and brain metastases), their informal caregivers, and health care professionals (HCPs) were included. Results Phase I (n = 44 patient-proxy dyads and 26 HCPs) generated 59 relevant and important activities. In phase II, the activities were converted into items. In phase III (n = 85 dyads), the 59 items were pre-tested. Item selection procedures resulted in 32 items. Exploratory factor analysis revealed a preliminary dimensional structure consisting of five scales with acceptable to excellent internal consistency (alpha = 0.73-0.94) and two single items. For three scales, patients with cognitive impairments had significantly more IADL problems than patients without impairments. Conclusion A phase IV validation study is needed to confirm the psychometric properties of the EORTC IADL-BN32 questionnaire in a larger international sample. Show less
Najafabadi, A.H.Z.; Meer, P.B. van der; Boele, F.W.; Taphoorn, M.J.B.; Klein, M.; Peerdeman, S.M.; ... ; Dutch Meningioma Consortium 2021
BACKGROUND: Many intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention.OBJECTIVE: To assess the long... Show moreBACKGROUND: Many intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention.OBJECTIVE: To assess the long-term (>= 5 yr) disease burden of meningioma patients.METHODS: In this multicenter cross-sectional study, patients >= 5 yr after intervention (including active magnetic resonance imaging (MRI) surveillance) were included and assessed for HRQoL (Short-Form Health Survey 36), neurocognitive functioning (neuropsychological assessment), anxiety and depression (Hospital Anxiety and Depression Scale), and work productivity (Short Form-Health and Labour Questionnaire). Multivariable and propensity score regression analyses were used to compare patients and controls, and different treatment strategies corrected for possible confounders. Clinically relevant differences were reported.RESULTS: At amedian of 9 yr follow-up after intervention, meningioma patients (n = 190) reported more limitations due to physical (difference 12.5 points, P = .008) and emotional (13.3 points, P = .002) health problems compared with controls. Patients also had an increased risk to suffer from anxiety (odds ratio [OR]: 2.6, 95% CI: 1.2-5.7) and depression (OR: 3.7, 95% CI: 1.3-10.5). Neurocognitive deficits were found in 43% of patients. Although postoperative complications, radiotherapy, and reresection were associated with worse verbal memory, attention, and executive functioning when compared to patients resected once, the only clinically relevant association was between reresection and worse attention (-2.11, 95% CI: -3.52 to -0.07). Patients of working age less often had a paid job (48%) compared with the working-age Dutch population (72%) and reported more obstacles at work compared with controls.CONCLUSION: In the long term, a large proportion of meningioma patients have impaired HRQoL, neurocognitive deficits, and high levels of anxiety or depression. Patients treated with 1 resection have the best neurocognitive functioning. Show less
Weller, M.; Bent, M. van den; Preusser, M.; Rhun, E. le; Tonn, J.C.; Minniti, G.; ... ; Wick, W. 2020
In response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need... Show moreIn response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy - Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers.Herein, the European Association of Neuro-Oncology (EANO) provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. These evidence-based guidelines incorporate major changes in diagnostic algorithms based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System as well as on evidence from recent large clinical trials. Show less
Simple Summary: Health-related quality of life (HRQoL) is an important outcome in glioma patients, as it reflects the patient's perspective on their functioning and wellbeing through the disease... Show moreSimple Summary: Health-related quality of life (HRQoL) is an important outcome in glioma patients, as it reflects the patient's perspective on their functioning and wellbeing through the disease course. The aim of our systematic review was to provide an overview of how HRQoL data is currently analyzed and interpreted in glioma studies. We found that the number of studies including HRQoL data increased in the past decade, but that assessment and analytical methods were highly variable. Ways to maximize information obtained with HRQoL questionnaires include appropriate and complementary analyses at both the group and individual level, comprehensive reporting of HRQoL results, and adherence to existing guidelines on the assessment, analysis, reporting and interpretation of patient-reported outcomes. This may ultimately result in high quality information that is relevant to inform physicians, patients and their relatives about the impact of the disease and its treatment on the patients' functioning and well-being.Background: Health-related quality of life (HRQoL) has become an increasingly important patient-reported outcome in glioma studies. Ideally, collected HRQoL data should be exploited to the full, with proper analytical methods. This systematic review aimed to provide an overview on how HRQoL data is currently evaluated in glioma studies, focusing on the research objectives and statistical analyses of HRQoL data. Methods: A systematic literature search in the databases PubMed, Embase, Web of Science and Cochrane was conducted up to 5 June 2020. Articles were selected based on predetermined inclusion criteria and information on study design, HRQoL instrument, HRQoL research objective and statistical methods were extracted. Results: A total of 170 articles describing 154 unique studies were eligible, in which 17 different HRQoL instruments were used. HRQoL was the primary outcome in 62% of the included articles, and 51% investigated >= 1 research question with respect to HRQoL, for which various analytical methods were used. In only 42% of the articles analyzing HRQoL results over time, the minimally clinical important difference was reported and interpreted. Eighty-six percent of articles reported HRQoL results at a group level only, and not at the individual patient level. Conclusion: Currently, the assessment and analysis of HRQoL outcomes in glioma studies is highly variable. Opportunities to maximize information obtained with HRQoL data include appropriate and complementary analyses at both the group and individual level, comprehensive reporting of HRQoL results in separate articles or supplementary material, and adherence to existing guidelines about the assessment, analysis and reporting of patient-reported outcomes. Show less
Background. Different analytical methods may lead to different conclusions about the impact of treatment on health-related quality of life (HRQoL). This study aimed to examine 3 different methods... Show moreBackground. Different analytical methods may lead to different conclusions about the impact of treatment on health-related quality of life (HRQoL). This study aimed to examine 3 different methods to evaluate change in HRQoL and to study whether these methods result in different conclusions.Methods. HRQoL data from 15 randomized clinical trials were combined (CODAGLIO project). Change in HRQoL scores, measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and BN20 questionnaires, was analyzed in 3 ways: (1) at the group level, comparing mean changes in scale/item scores between treatment arms, (2) at the patient level per scale/item, calculating the percentage of patients that deteriorated, improved, or remained stable per scale/item, and (3) at the individual patient level, combining all scales/items.Results. Baseline and first follow-up HRQoL data were available for 3727 patients. At the group scale/item level, only the item "hair loss" showed a significant and clinically relevant change (ie, >= 10 points) over time, whereas change scores on the other scales/items were statistically significant only (all P <.001; range in change score, 0.1-6.2). Although a large proportion of patients had stable HRQoL over time (range, 27%-84%) on the patient level per scale/item, many patients deteriorated (range, 6%-43%) or improved (range, 8%-32%) on a specific scale/item. At the individual patient level, the majority of patients (86%) showed both deterioration and improvement, whereas only 1% remained stable on all scales.Conclusions. Different analytical methods of changes in HRQoL result in distinct conclusions of treatment effects, all of which may be relevant for informing clinical decision making. Show less
Najafabadi, A.H.Z.; Meer, P.B. van der; Boele, F.W.; Taphoorn, M.J.B.; Klein, M.; Peerdeman, S.M.; ... ; Dirven, L. 2020
Introduction Meningioma is a heterogeneous disease and patients may suffer from long-term tumor- and treatment-related sequelae. To help identify patients at risk for these late effects, we first... Show moreIntroduction Meningioma is a heterogeneous disease and patients may suffer from long-term tumor- and treatment-related sequelae. To help identify patients at risk for these late effects, we first assessed variables associated with impaired long-term health-related quality of life (HRQoL) and impaired neurocognitive function on group level (i.e. determinants). Next, prediction models were developed to predict the risk for long-term neurocognitive or HRQoL impairment on individual patient-level. Methods Secondary data analysis of a cross-sectional multicenter study with intracranial WHO grade I/II meningioma patients, in which HRQoL (Short-Form 36) and neurocognitive functioning (standardized test battery) were assessed. Multivariable regression models were used to assess determinants for these outcomes corrected for confounders, and to build prediction models, evaluated with C-statistics. Results Data from 190 patients were analyzed (median 9 years after intervention). Main determinants for poor HRQoL or impaired neurocognitive function were patients' sociodemographic characteristics, surgical complications, reoperation, radiotherapy, presence of edema, and a larger tumor diameter on last MRI. Prediction models with a moderate/good ability to discriminate between individual patients with and without impaired HRQoL (C-statistic 0.73, 95% CI 0.65 to 0.81) and neurocognitive function (C-statistic 0.78, 95%CI 0.70 to 0.85) were built. Not all predictors (e.g. tumor location) within these models were also determinants. Conclusions The identified determinants help clinicians to better understand long-term meningioma disease burden. Prediction models can help early identification of individual patients at risk for long-term neurocognitive or HRQoL impairment, facilitating tailored provision of information and allocation of scarce supportive care services to those most likely to benefit. Show less
