Influence of arterial transit time delays on the differentiation between tumor progression and pseudoprogression in glioblastoma by arterial spin labeling magnetic resonance imaging.

Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) have shown potential for differentiating tumor progression from pseudoprogression. For pseudocontinuous ASL with a single postlabeling delay, the presence of delayed arterial transit times (ATTs) could affect the evaluation of ASL-MRI perfusion data. In this study, the influence of ATT artifacts on the perfusion assessment and differentiation between tumor progression and pseudoprogression were studied. This study comprised 66 adult patients (mean age 60 ± 13 years; 40 males) with a histologically confirmed glioblastoma who received postoperative radio (chemo)therapy. ASL-MRI and DSC-MRI scans were acquired at 3 months postradiotherapy as part of the standard clinical routine. These scans were visually scored regarding (i) the severity of ATT artifacts (%) on the ASL-MRI scans only, scored by two neuroradiologists; (ii) perfusion of the enhancing tumor lesion; and (iii) radiological evaluation of tumor progression versus pseudoprogression by one neuroradiologist. The final outcome was based on combined clinical and radiological follow-up until 9 months postradiotherapy. ATT artifacts were identified in all patients based on the mean scores of two raters. A significant difference between the radiological evaluation of ASL-MRI and DSC-MRI was observed only for ASL images with moderate ATT severity (30%-65%). The perfusion assessment showed ASL-MRI tending more towards hyperperfusion than DSC-MRI in the case of moderate ATT artifacts. In addition, there was a significant difference between the prediction of tumor progression with ASL-MRI and the final outcome in the case of severe ATT artifacts (McNemar test, p = 0.041). Despite using ASL imaging parameters close to the recommended settings, ATT artifacts frequently occur in patients with treated brain tumors. Those artifacts could hinder the radiological evaluation of ASL-MRI data and the detection of true disease progression, potentially affecting treatment decisions for patients with glioblastoma.

Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI): stakeholder views, objectives, and procedures.

Patient-reported outcomes (PROs), such as symptoms, functioning, and other health-related quality-of-life concepts are gaining a more prominent role in the benefit-risk assessment of cancer therapies. However, varying ways of analysing, presenting, and interpreting PRO data could lead to erroneous and inconsistent decisions on the part of stakeholders, adversely affecting patient care and outcomes. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) Consortium builds on the existing SISAQOL work to establish recommendations on design, analysis, presentation, and interpretation for PRO data in cancer clinical trials, with an expanded set of topics, including more in-depth recommendations for randomised controlled trials and single-arm studies, and for defining clinically meaningful change. This Policy Review presents international stakeholder views on the need for SISAQOL-IMI, the agreed on and prioritised set of PRO objectives, and a roadmap to ensure that international consensus recommendations are achieved.

First-line levetiracetam versus enzyme-inducing antiseizure medication in glioma patients with epilepsy.

OBJECTIVE: This study aimed to directly compare the effectiveness of first-line monotherapy levetiracetam (LEV) versus enzyme-inducing antiseizure medications (EIASMs) in glioma patients. METHODS: In this nationwide retrospective observational cohort study, Grade 2-4 glioma patients were included, with a maximum duration of follow-up of 36 months. Primary outcome was antiseizure medication (ASM) treatment failure for any reason, and secondary outcomes were treatment failure due to uncontrolled seizures and due to adverse effects. For estimation of the association between ASM treatment and ASM treatment failure, multivariate cause-specific cox proportional hazard models were estimated, adjusting for potential confounders. RESULTS: In the original cohort, a total of 808 brain tumor patients with epilepsy were included, of whom 109 glioma patients were prescribed first-line LEV and 183 glioma patients first-line EIASMs. The EIASM group had a significantly higher risk of treatment failure for any reason compared to LEV (adjusted hazard ratio [aHR] = 1.82, 95% confidence interval [CI] = 1.20-2.75, p = .005). Treatment failure due to uncontrolled seizures did not differ significantly between EIASMs and LEV (aHR = 1.32, 95% CI = .78-2.25, p = .300), but treatment failure due to adverse effects differed significantly (aHR = 4.87, 95% CI = 1.89-12.55, p = .001). SIGNIFICANCE: In this study, it was demonstrated that LEV had a significantly better effectiveness (i.e., less ASM treatment failure for any reason or due to adverse effects) compared to EIASMs, supporting the current neuro-oncology guideline recommendations to avoid EIASMs in glioma patients.

Healthcare utilization and costs among intracranial meningioma patients during long-term follow-up.

PURPOSE: Few studies have reported on healthcare utilization and costs for intracranial meningioma patients, while the tumor and its treatment profoundly affect patients' functioning and well-being. Here we evaluated healthcare utilization and costs, including their determinants. METHODS: A multicenter cross-sectional study of adult meningioma patients ≥ 5 years after intervention. Patients completed three validated patient-reported outcome measures (PROMs) assessing patients 'functioning and wellbeing (SF-36, EORTC QLQ-BN20, and HADS) and a study-specific questionnaire assessing healthcare utilization over the previous twelve months. Healthcare costs of the twelve months prior were calculated using reported healthcare utilization ≥ 5 years after intervention by the Dutch Manual for Economic Evaluation in Healthcare. Determinants for healthcare utilization and costs were determined with regression analyses. RESULTS: We included 190 patients with WHO grade I or II meningioma after a mean follow-up since intervention of 9.2 years (SD 4.0). The general practitioner (80.5%), physiotherapist (37.9%), and neurologist (25.4%) were visited most often by patients. Median annual healthcare costs were €871 (IQR €262-€1933). Main contributors to these costs were medication (45.8% of total costs, of which anti-seizure medication was utilized most [21.6%]), specialist care (17.7%), and physiotherapy (15.5%). Lower HRQoL was a significant determinant for higher healthcare utilization and costs. CONCLUSION: In patients with meningioma, medication costs constituted the largest expenditure of total healthcare costs, in particular anti-seizure medication. Particularly a lower HRQoL was a determinant for healthcare utilization and costs. A patient-specific approach aimed at improving patients' HRQoL and needs could be beneficial in reducing disease burden and functional recovery.

Impact of timing of antiseizure medication withdrawal on seizure recurrence in glioma patients: a retrospective observational study.

BACKGROUND: Withdrawal of antiseizure medication treatment (ASM) can be considered after completion of antitumour treatment in glioma patients who no longer suffer from seizures. We compared the risk for recurrent seizures after ASM withdrawal between patients with short-term, medium-term versus long-term seizure freedom after antitumour treatment. METHODS: In this retrospective observational study, the primary outcome was time to recurrent seizure, from the starting date of no ASM treatment up to 36 months follow-up. Cox proportional hazards models were used to study the effect of risk factors on time to recurrent seizure. Stratification was done with information known at baseline. Short-term seizure freedom was defined as ≥ 3 months, but < 12 months; medium-term as 12-24 months; and long-term as ≥ 24 months seizure freedom from the date of last antitumour treatment. RESULTS: This study comprised of 109 patients; 31% (34/109) were in the short-term, 29% (32/109) in the medium-term, and 39% (43/109) in the long-term group. A recurrent seizure was experienced by 47% (16/34) of the patients in the short-term, 31% (10/32) in the medium-term, and 44% (19/43) in the long-term group. Seizure recurrence risk was similar between patients in the short-term group as compared to the medium-term (cause-specific adjusted hazard ratio [aHR] = 0.65 [95%CI = 0.29-1.46]) and long-term group (cause-specific aHR = 1.04 [95%CI = 0.52-2.09]). CONCLUSIONS: Seizure recurrence risk is relatively similar between patients with short-term, medium-term, and long-term seizure freedom after completion of antitumour treatment.

Health-Related Quality of Life in Intracranial Meningioma: Current Evidence and Future Directions.

Historically, largely due to the good prognosis for survival, there has been little attention paid to the possible impact of meningiomas and their treatment on health-related quality of life (HRQoL). However, in the last decade there has been increasing evidence that patients with intracranial meningiomas suffer from long-term decreases in their HRQoL. Compared with controls and normative data, meningioma patients have worse HRQoL scores both before and after intervention and continuing long term (even after >4 years of follow-up). Overall, surgery results in improvements in many aspects of HRQoL. The limited available studies investigating the impact of radiotherapy suggest that this type of treatment decreases HRQoL scores, especially in the long term. There is however only limited evidence on additional determinants of HRQoL. Patients with anatomically complex skull base meningiomas and severe comorbidities, including epilepsy, report the lowest HRQoL scores. Other tumor and sociodemographic characteristics have shown weak associations with HRQoL. Furthermore, about one-third of caregivers of meningioma patients report caregiver burden, warranting interventions to improve caregiver HRQoL. As antitumor interventions may not improve HRQoL scores to be comparable to those of the general population, more attention should be paid to the development of integrative rehabilitation and supportive care programs for meningioma patients.

Is the EORTC QLQ-C30 emotional functioning scale appropriate as an initial screening measure to identify brain tumour patients who may possibly have a mood disorder?

BACKGROUND: Screening glioma patients regularly for possible mood disorders may facilitate early identification and referral of patients at risk. This study evaluated if the EORTC QLQ-C30 Emotional Functioning (EF) scale could be used as an initial screening measure to identify patients possibly having a mood disorder. METHODS: EORTC QLQ-C30 EF and Hospital Anxiety and Depression Scale (HADS) scores were collected as part of a study assessing the impact of timing of patient-reported outcome assessments on actual health-related quality of life outcomes (N = 99). Spearman correlations and Mann-Whitney U tests were used to determine the association between the EF and HADS (sub)scales. Receiver Operating Characteristic analyses were performed to determine optimal cut-off EF scores to identify patients possibly having a mood disorder (i.e. HADS subscale score ≥8 points). RESULTS: EF and HADS (sub)scales correlated moderately (HADS-A: r = -0.65; HADS-D: r = -0.52). Significant EF score differences were found between patients with HADS ≥8 versus <8 points (HADS-A: mean difference (MD) = 32 and HADS-D: MD = 23). The EF scale had excellent (HADS-A; AUC = 0.88) and borderline excellent (HADS-D; AUC = 0.78) distinguishing capabilities. A statistically optimal (EF score <80) and a most inclusive (sensitivity of 100%, corresponding to an EF score <97) EF cut-off score correctly identified 88.0% and 96.0% of patients with a possible mood disorder, respectively. CONCLUSION: EORTC QLQ-C30 EF scale seems to be an appropriate screening measure to identify glioma patients possibly having a mood disorder in need of further assessment.

Developing an e-learning course on the use of PRO measures in oncological practice: health care professionals' preferences for learning content and methods.

PURPOSE: Implementation of patient-reported outcome measures (PROMs) in clinical routine requires knowledge and competences regarding their use. In order to facilitate implementation, an e-learning course for health care professionals (HCPs) on the utilisation of European Organisation for Research and Treatment of Cancer (EORTC) PROMs in oncological clinical practice is being developed. This study aimed to explore future users' educational needs regarding content and learning methods. METHODS: The sequential mixed methods approach was applied. A scoping literature review informed the guideline for qualitative interviews with HCPs with diverse professional backgrounds in oncology and cancer advocates recruited using a purposive sampling strategy. An international online survey was conducted to validate the qualitative findings. RESULTS: Between December 2019 and May 2020, 73 interviews were conducted in 9 countries resulting in 8 topic areas (Basic information on PROs in clinical routine, Benefits of PRO assessments in clinical practice, Implementation of PRO assessments in clinical routine, Setup of PRO assessments for clinical application, Interpretation of PRO data, Integration of PROs into the communication with patients, Use of PROs in clinical practice, Self-management recommendations for patients based on PROs) subsequently presented in the online survey. The online survey (open between 3 June and 19 July 2020) was completed by 233 HCPs from 33 countries. The highest preference was indicated for content on interpretation of PRO data (97%), clinical benefits of assessing PRO data (95.3%) and implementation of routine PRO data assessment (94.8%). Regarding learning methods, participants indicated a high preference for practical examples that use a mixed approach of presentation (written, audio, video and interactive). CONCLUSION: Educational needs for an integration of PROs in communication in clinical care and coherent implementation strategies became evident. These results inform the development of an e-learning course to support HCPs in the clinical use of EORTC PRO measures.

Neurocognitive impairment and patient-proxy agreement on health-related quality of life evaluations in recurrent high-grade glioma patients.

PURPOSE: The rate of missing data on patient-reported health-related quality of life (HRQOL) in brain tumor clinical trials is particularly high over time. One solution to this issue is the use of proxy (i.e., partner, relative, informal caregiver) ratings in lieu of patient-reported outcomes (PROs). In this study we investigated patient-proxy agreement on HRQOL outcomes in high-grade glioma (HGG) patients. METHODS: Generic and disease-specific HRQOL were assessed using the EORTC QLQ-C30 and QLQ-BN20 in a sample of 501 patient-proxy dyads participating in EORTC trials 26101 and 26091. Patients were classified as impaired or intact, based on their neurocognitive performance. The level of patient-proxy agreement was measured using Lin's concordance correlation coefficient (CCC) and the Bland-Altman limit of agreement. The Wilcoxon signed-rank test was used to evaluate differences between patients' and proxies' HRQOL. RESULTS: Patient-proxy agreement in all HGG patients (N = 501) ranged from 0.082 to 0.460. Only 18.8% of all patients were neurocognitively intact. Lin's CCC ranged from 0.088 to 0.455 in cognitively impaired patients and their proxies and from 0.027 to 0.538 in cognitively intact patients and their proxies. CONCLUSION: While patient-proxy agreement on health-related quality of life outcomes is somewhat higher in cognitively intact patients, agreement in high-grade glioma patients is low in general. In light of these findings, we suggest to cautiously consider the use of proxy's evaluation in lieu of patient-reported outcomes, regardless of patient's neurocognitive status.

Meningioma systematic reviews and meta-analyses: an assessment of reporting and methodological quality.

INTRODUCTION: Systematic reviews (SR) and systematic reviews with meta-analysis (SRMA) can constitute the highest level of research evidence. Such evidence syntheses are relied upon heavily to inform the clinical knowledge base and to guide clinical practice for meningioma. This review evaluates the reporting and methodological quality of published meningioma evidence syntheses to date. METHODS: Eight electronic databases/registries were searched to identify eligible meningioma SRs with and without meta-analysis published between January 1990 and December 2020. Articles concerning spinal meningioma were excluded. Reporting and methodological quality were assessed against the following tools: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2), and Risk Of Bias in Systematic reviews (ROBIS). RESULTS: 116 SRs were identified, of which 57 were SRMAs (49.1%). The mean PRISMA score for SRMA was 20.9 out of 27 (SD 3.9, 77.0% PRISMA adherence) and for SR without meta-analysis was 13.8 out of 22 (SD 3.4, 63% PRISMA adherence). Thirty-eight studies (32.8%) achieved greater than 80% adherence to PRISMA. Methodological quality assessment against AMSTAR 2 revealed that 110 (94.8%) studies were of critically low quality. Only 21 studies (18.1%) were judged to have a low risk of bias against ROBIS. CONCLUSION: The reporting and methodological quality of meningioma evidence syntheses was poor. Established guidelines and critical appraisal tools may be used as an adjunct to aid methodological conduct and reporting of such reviews, in order to improve the validity and transparency of research which may influence clinical practice.

First-line antiepileptic drug treatment in glioma patients with epilepsy: Levetiracetam vs valproic acid.

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 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.

MMSE is an independent prognostic factor for survival in primary central nervous system lymphoma.

INTRODUCTION: To assess the value of the Mini-Mental State Examination (MMSE)-score at baseline in predicting survival in adult primary central nervous system lymphoma (PCNSL) patients. METHODS: In the HOVON 105/ ALLG NHL 24 phase III study patients with newly-diagnosed PCNSL were randomized between high-dose methotrexate-based chemotherapy with or without rituximab. Data on potential (MMSE-score), and known baseline prognostic factors (age, performance status, serum LDH, cerebrospinal fluid total protein, involvement of deep brain structures, multiple cerebral lesions, and the IELSG-score) were collected prospectively. Multivariable stepwise Cox regression analyses were used to assess the prognostic value of all factors on progression-free survival (PFS) and overall survival (OS) among patients with available MMSE score at baseline. Age was analyzed as continuous variable, the MMSE-score both as a continuous and as a categorical variable. RESULTS: In univariable analysis, age, MMSE-score and whether the patient received rituximab were statistically significantly prognostic factors for PFS. Age and MMSE-score were statistically significantly associated with OS. In a multivariable analysis of the univariately significant factors only MMSE-score was independently associated with the survival endpoints, as a continuous variable (HR for PFS 1.04, 95% CI 1.01-1.08; OS 1.06 (95% CI 1.02-1.10) and as categorical variable HR (< 27 versus ≥ 27 for PFS 1.55 (1.02-2.35); OS 1.68 (1.05-2.70). In our population, performance status, serum LDH, and CSF protein level were not of prognostic value. CONCLUSION: Neurocognitive disturbances, measured with the MMSE at baseline, are an unfavorable prognostic factor for both PFS and OS in adult PCNSL patients up to 70 years-old.

Effect of antiepileptic drugs in glioma patients on self-reported depression, anxiety, and cognitive complaints.

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 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.

The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide.

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 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.

eHealth cognitive rehabilitation for brain tumor patients: results of a randomized controlled trial.

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 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.

Determinants and predictors for the long-term disease burden of intracranial meningioma patients.

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 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.

Development of an EORTC questionnaire measuring instrumental activities of daily living (IADL) in patients with brain tumours: phase I-III.

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 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 (α = 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.

Glioma patient-reported outcome assessment in clinical care and research: a Response Assessment in Neuro-Oncology collaborative report.

Clinical trials of treatments for high-grade gliomas have traditionally relied on measures of response or time-dependent metrics; however, these endpoints have limitations because they do not characterise the functional or symptomatic effect of the condition on the person. Including clinical outcome assessments, such as patient- reported outcomes (PROs), to determine net clinical benefit of a treatment strategy is needed because of the substantial burden of symptoms and impaired functioning in this patient population. The US National Cancer Institute convened a meeting to review previous recommendations and existing PRO measures of symptoms and function that can be applied to current trials and clinical practice for high-grade gliomas. Measures were assessed for relevance, relationship to disease and therapy, sensitivity to change, psychometric properties, response format, patient acceptability, and use of self-report. The group also relied on patient input including the results of an online survey, a literature review on available clinical outcomes, expert opinion, and alignment with work done by other organisations. A core set of priority constructs was proposed that allows more comprehensive evaluation of therapies and comparison of outcomes among studies, and enhances efforts to improve the measurement of these core clinical outcomes. The proposed set of constructs was then presented to the Society for Neuro-Oncology Response Assessment in Neuro-Oncology Working Group and feedback was solicited.

The impact of current treatment modalities on the outcomes of patients with melanoma brain metastases: A systematic review.

Patients with melanoma brain metastases (MBM) still have a very poor prognosis. Several treatment modalities have been investigated in an attempt to improve the management of MBM. This review aimed to evaluate the impact of current treatments for MBM on patient- and tumor-related outcomes, and to provide treatment recommendations for this patient population. A literature search in the databases PubMed, Embase, Web of Science and Cochrane was conducted up to January 8, 2019. Original articles published since 2010 describing patient- and tumor-related outcomes of adult MBM patients treated with clearly defined systemic therapy were included. Information on basic trial demographics, treatment under investigation and outcomes (overall and progression-free survival, local and distant control and toxicity) were extracted. We identified 96 eligible articles, comprising 95 studies. A large variety of treatment options for MBM were investigated, either used alone or as combined modality therapy. Combined modality therapy was investigated in 71% of the studies and resulted in increased survival and better distant/local control than monotherapy, especially with targeted therapy or immunotherapy. However, neurotoxic side-effects also occurred more frequently. Timing appeared to be an important determinant, with the best results when radiotherapy was given before or during systemic therapy. Improved tumor control and prolonged survival can be achieved by combining radiotherapy with immunotherapy or targeted therapy. However, more randomized controlled trials or prospective studies are warranted to generate proper evidence that can be used to change the standard of care for patients with MBM.

Prediagnostic symptoms and signs of adult glioma: the patients' view.

BACKGROUND: Little is known about the symptoms glioma patients experience in the year before diagnosis, either or not resulting in health care usage. This study aimed to determine the incidence of symptoms glioma patients experienced in the year prior to diagnosis, and subsequent visits to a general practitioner (GP). METHODS: Glioma patients were asked to complete a 30-item study-specific questionnaire focusing on symptoms they experienced in the 12 months before diagnosis. For each indicated symptom, patients were asked whether they consulted the GP for this issue. RESULTS: Fifty-nine patients completed the questionnaires, 54 (93%) with input of a proxy. The median time since diagnosis was 4 months (range 1-12). The median number of symptoms experienced in the year before diagnosis was similar between gliomas with favourable and poor prognosis, i.e. 6 (range 0-24), as were the five most frequently mentioned problems: fatigue (n = 34, 58%), mental tiredness (n = 30, 51%), sleeping disorder (n = 24, 41%), headache (n = 23, 39%) and stress (n = 20, 34%). Twenty-six (44%) patients visited the GP with at least one issue. Patients who did consult their GP reported significantly more often muscle weakness (11 vs 3, p = 0.003) than patients who did not, which remained significant after correction for multiple testing, which was not the case for paralysis in hand/leg (10 vs 4), focussing (11 vs 6) or a change in awareness (9 vs 4). CONCLUSIONS: Glioma patients experience a range of non-specific problems in the year prior to diagnosis, but only patients who consult the GP report more often neurological problems.