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Abstract Background Cancer patients may experience a decrease in cognitive functioning before, during and after cancer treatment. So far, the Quality of Life Group of the European Organisation for Research and Treatment of Cancer (EORTC QLG) developed an item bank to assess self-reported memory and attention within a single, cognitive functioning scale (CF) using computerized adaptive testing (EORTC CAT Core CF item bank). However, the distinction between different cognitive functions might be important to assess the patients’ functional status appropriately and to determine treatment impact. To allow for such assessment, the aim of this study was to develop and psychometrically evaluate separate item banks for memory and attention based on the EORTC CAT Core CF item bank. Methods In a multistep process including an expert-based content analysis, we assigned 44 items from the EORTC CAT Core CF item bank to the memory or attention domain. Then, we conducted psychometric analyses based on a sample used within the development of the EORTC CAT Core CF item bank. The sample consisted of 1030 cancer patients from Denmark, France, Poland, and the United Kingdom. We evaluated measurement properties of the newly developed item banks using confirmatory factor analysis (CFA) and item response theory model calibration. Results Item assignment resulted in 31 memory and 13 attention items. Conducted CFAs suggested good fit to a 1-factor model for each domain and no violations of monotonicity or indications of differential item functioning. Evaluation of CATs for both memory and attention confirmed well-functioning item banks with increased power/reduced sample size requirements (for CATs ≥ 4 items and up to 40% reduction in sample size requirements in comparison to non-CAT format). Conclusion Two well-functioning and psychometrically robust item banks for memory and attention were formed from the existing EORTC CAT Core CF item bank. These findings could support further research on self-reported cognitive functioning in cancer patients in clinical trials as well as for real-word-evidence. A more precise assessment of attention and memory deficits in cancer patients will strengthen the evidence on the effects of cancer treatment for different cancer entities, and therefore contribute to shared and informed clinical decision-making.

Gliomas are highly heterogeneous and often include a nonenhancing component that is hyperintense on T 2 weighted MRI. This can often not be distinguished from secondary gliosis and surrounding edema. We hypothesized that the extent of these T 2 hyperintense areas can more accurately be determined on high-quality 7 T MRI scans. We investigated the extension, volume, and complexity (shape) of T 2 hyperintense areas in patients with glioma on high-quality 7 T MRI scans compared to clinical MRI scans. T 2 hyperintense areas of 28 patients were visually compared and manually segmented on 7 T MRI and corresponding clinical (1.5 T/3 T) MRI scans, and the volume and shape markers were calculated and subsequently compared between scans. We showed extension of the T 2 hyperintense areas via the corpus callosum to the opposite hemisphere in four patients on the 7 T scans that was not visible on the clinical scan. Furthermore, we found a significantly larger volume of the T 2 hyperintense areas on the 7 T scans compared with the clinical scans (7 T scans: 28 mL [12.5-59.1]; clinical scans: 11.9 mL [11.8-56.6]; p = 0.01). We also found a higher complexity of the T 2 hyperintense areas on the 7 T scans compared with the clinical scans (convexity, solidity, concavity index and fractal dimension [p < 0.001]). Our study suggests that high-quality 7 T MRI scans may show more detail on the exact extension, size, and complexity of the T 2 hyperintense areas in patients with a glioma. This information could aid in more accurate planning of treatment, such as surgery and radiotherapy., (© 2025 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Background: Neurocognitive impairments are common in patients with a brain tumour, and may negatively impact on functioning in daily life, particularly on instrumental activities of daily living (IADL). The EORTC IADL-BN32 questionnaire was developed to measure IADL in this patient population., Methods: In this international validation study, we evaluated the EORTC IADL-BN32 questionnaire on several psychometric properties in a large sample of patients with a primary or metastatic brain tumour. We administered the 32-item questionnaire three times: at 'baseline', after 2 weeks and after 3 months. Procedures were in accordance with EORTC Quality of Life Group module development guidelines., Results: In total, 326 patients participated in the study. A bifactor scale structure showed satisfactory model fit measures, with five multi-item scales and two single items, and an IADL sum score. The internal consistency of the multi-item scales ranged from good to excellent (range Cronbach's α: 0.86-0.97). We found significant differences in scale scores between patients with and without neurocognitive impairments or complaints, supporting the construct validity. Initial cross-cultural validity analyses showed indications of item response biases for certain items. Analyses indicated moderate to good test-retest agreement (intraclass correlation coefficient > 0.70) between baseline and the 2-week follow-up assessment for all but one scale. Deterioration of EORTC IADL-BN32 scale scores were consistent with clinically relevant deterioration on other functional measures with small to large effect sizes, however, subgroup sample sizes were small., Conclusion: Overall, the EORTC IADL-BN32 questionnaire exhibited adequate to excellent psychometric properties. Cross-cultural validity and responsiveness should be further explored., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Gliomas are primary brain tumours that are thought to develop from neural stem or progenitor cells that carry tumour-initiating genetic alterations. Based on microscopic appearance and molecular characteristics, they are classified according to the WHO classification of central nervous system (CNS) tumours and graded into CNS WHO grades 1-4 from a low to high grade of malignancy. Diffusely infiltrating gliomas in adults comprise three tumour types with distinct natural course of disease, response to treatment and outcome: isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted oligodendrogliomas with the best prognosis; IDH-mutant astrocytomas with intermediate outcome; and IDH-wild-type glioblastomas with poor prognosis. Pilocytic astrocytoma is the most common glioma in children and is characterized by circumscribed growth, frequent BRAF alterations and favourable prognosis. Diffuse gliomas in children are divided into clinically indolent low-grade tumours and high-grade tumours with aggressive behaviour, with histone 3 K27-altered diffuse midline glioma being the leading cause of glioma-related death in children. Ependymal tumours are subdivided into biologically and prognostically distinct types on the basis of histology, molecular biomarkers and location. Although surgery, radiotherapy and alkylating agent chemotherapy are the mainstay of glioma treatment, individually tailored strategies based on tumour-intrinsic dominant signalling pathways have improved outcome in subsets of patients., (© 2024. Springer Nature Limited.)

Background: Studies on the efficacy of rituximab in primary CNS lymphoma (PCNSL) reported conflicting results. Our international randomized phase 3 study showed that the addition of rituximab to high-dose methotrexate, BCNU, teniposide, and prednisolone (MBVP) in PCNSL was not efficacious in the short term. Here we present long-term results after a median follow-up of 82.3 months., Methods: One hundred and ninety-nine eligible newly diagnosed, nonimmunocompromised patients with PCNSL aged 18-70 years with WHO performance status 0-3 was randomized between treatment with MBVP chemotherapy with or without rituximab, followed by high-dose cytarabine consolidation in responding patients, and reduced-dose WBRT in patients aged ≤ 60 years. Event-free survival was the primary endpoint. Overall survival rate, neurocognitive functioning (NCF), and health-related quality of life (HRQoL) were additionally assessed, with the IPCG test battery, EORTC QLQ-C30 and QLQ-BN20 questionnaires, respectively., Results: For event-free survival, the hazard ratio was 0.85, 95% CI 0.61-1.18, P = .33. Overall survival rate at 5 years for MBVP and R-MBVP was 49% (39-59) and 53% (43-63) respectively. In total, 64 patients died in the MBVP arm and 55 in the R-MBVP arm, of which 69% were due to PCNSL. At the group level, all domains of NCF and HRQoL improved to a clinically relevant extent after treatment initiation, and remained stable thereafter up to 60 months of follow-up, except for motor speed which deteriorated between 24 and 60 months. Although fatigue improved initially, high levels persisted in the long term., Conclusions: Long-term follow-up confirms the lack of added value of rituximab in addition to MBVP and HD-cytarabine for PCNSL., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background: The clinical management of patients with incidental intracranial meningioma varies markedly and is often based on clinician choice and observational data. Heterogeneous outcome measurement has likely hampered knowledge progress by preventing comparative analysis of similar cohorts of patients. This systematic review aimed to summarize the outcomes measured and reported in observational studies., Methods: A systematic literature search was performed to identify published full texts describing active monitoring of adult cohorts with incidental and untreated intracranial meningioma (PubMed, EMBASE, MEDLINE, and CINAHL via EBSCO, completed January 24, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were de-duplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the "Core Outcome Measures in Effectiveness Trials" (COMET) initiative., Results: Thirty-three published articles and 1 ongoing study were included describing 32 unique studies: study designs were retrospective n  = 27 and prospective n  = 5. In total, 268 verbatim outcomes were reported, of which 77 were defined. Following de-duplication, 178 unique verbatim outcomes remained and were grouped into 53 standardized outcome terms. These were classified using the COMET taxonomy into 9 outcome domains and 3 core areas., Conclusions: Outcome measurement across observational studies of incidental and untreated intracranial meningioma is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a Core Outcome Set for use in future observational studies., Competing Interests: M.D.J. received a grant from the National Institute for Health Research Health Technology Assessment program for the Radiation versus Observation for Atypical Meningioma (ROAM) trial (NIHR ID: 12/173/14). M.D.J. and S.J.M. received a grant from the National Institute for Health Research Health Technology Assessment program for Surgeons Trial Of Prophylaxis for Epilepsy in seizure naïve patients with Meningioma (STOP’EM) (NIHR ID: NIHR129748). T.S. founded and leads the Anaplastic Meningioma International Consortium (AMiCo). T.S. and M.D.J. cofounded the British-Irish Meningioma Society (BIMS). A.G.M. is a National Institute for Health Research (NIHR) Senior Investigator and is also part-funded by NIHR ARC North West Coast. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. M.P. has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Servier. M.W. has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche and Sandoz., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Neuro-oncology patients and caregivers should have equitable access to rehabilitation, supportive-, and palliative care. To investigate existing issues and potential solutions, we surveyed neuro-oncology professionals to explore current barriers and facilitators to screening patients' needs and referral to services., Methods: Members of the European Association of Neuro-Oncology and the European Organisation for Research and Treatment of Cancer Brain Tumor Group (EORTC-BTG) were invited to complete a 39-item online questionnaire covering the availability of services, screening, and referral practice. Responses were analyzed descriptively; associations between sociodemographic/clinical variables and screening/referral practice were explored., Results: In total, 103 participants completed the survey (67% women and 57% medical doctors). Fifteen professions from 23 countries were represented. Various rehabilitation, supportive-, and palliative care services were available yet rated "inadequate" by 21-37% of participants. Most respondents with a clinical role ( n  = 94) declare to screen (78%) and to refer (83%) their patients routinely for physical/cognitive/emotional issues. Survey completers ( n  = 103) indicated the main reasons for not screening/referring were (1) lack of suitable referral options (50%); (2) shortage of healthcare professionals (48%); and (3) long waiting lists (42%). To improve service provision, respondents suggested there is a need for education about neuro-oncology-specific issues (75%), improving the availability of services (65%) and staff (64%), developing international guidelines (64%), and strengthening the existing evidence-base for rehabilitation (60%)., Conclusions: Detecting and managing neuro-oncology patients' and caregivers' rehabilitation, supportive,- and palliative care needs can be improved. Better international collaboration can help address healthcare disparities., Competing Interests: B.F.: No COI. D.L.: No COI. D.K.M.: No COI. F.J.: honoraria for lectures and consultations from the following for-profit companies: Novartis, Seagen. G.N.: received honoraria for lectures from Blue Earth Diagnostics and for advisory board participation from Telix Pharmaceuticals. K.B.: No COI. L.R.E.: has received a grant from Bristol Meyer Squibb and honoraria for lectures or advisory board from Bayer, Janssen, Leo Pharma, Pierre Fabre, Roche, Seattle Genetics and Servier. M.S.: No COI. M.G.: reports personal financial interests as an invited speaker for BrainLab and treasurer for the EORTC. N.E.: No COI. N.S.: No COI. P.M.: received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Böhringer-Ingelheim, Telix, Medscape. R.L.: No COI. R.R.: has received honoraria for lectures or consultation or advisory board from the following companies: UCB, Novocure, Bayer, Servier, Cure-Vac. R.I.: No COI. T.M.: No COI. W.A.: No COI. C.A. Research funding and honoraria from AstraZeneca, Benevolent AI, Duke Street Bio. S.C.S.: Honoraria from Bayer, Chimerix; laboratory project support from Apollomics, Blue Earth Diagnostics; consultancy fees from CeCaVa, Miltenyi, Tocagen, Servier; travel support from Blue Earth Diagnostics. K.P.: No COI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Meningioma clinical trials have assessed interventions including surgery, radiotherapy, and pharmacotherapy. However, agreement does not exist on what, how, and when outcomes of interest should be measured. To do so would allow comparative analysis of similar trials. This systematic review aimed to summarize the outcomes measured and reported in meningioma clinical trials., Methods: Systematic literature and trial registry searches were performed to identify published and ongoing intracranial meningioma clinical trials (PubMed, Embase, Medline, CINAHL via EBSCO, and Web of Science, completed January 22, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were deduplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the "Core Outcome Measures in Effectiveness Trials" (COMET) initiative., Results: Thirty published articles and 18 ongoing studies were included, describing 47 unique clinical trials: Phase 2 n  = 33, phase 3 n  = 14. Common interventions included: Surgery n  = 13, radiotherapy n  = 8, and pharmacotherapy n  = 20. In total, 659 verbatim outcomes were reported, of which 84 were defined. Following de-duplication, 415 unique verbatim outcomes remained and were grouped into 115 standardized outcome terms. These were classified using the COMET taxonomy into 29 outcome domains and 5 core areas., Conclusions: Outcome measurement across meningioma clinical trials is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a core outcome set for use in future meningioma clinical trials., Competing Interests: MDJ received a grant from the National Institute for Health Research Health Technology Assessment program for the Radiation versus Observation for Atypical Meningioma (ROAM) trial (NIHR ID: 12/173/14). MDJ and SJM received a grant from the National Institute for Health Research Health Technology Assessment program for Surgeons Trial Of Prophylaxis for Epilepsy in seizure naïve patients with Meningioma (STOP’EM; NIHR ID: NIHR129748). TS founded and leads the Anaplastic Meningioma International Consortium (AMiCo). TS and MDJ co-founded the British-Irish Meningioma Society (BIMS). AGM is a National Institute for Health Research (NIHR) Senior Investigator and is also part-funded by NIHR ARC North West Coast. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR, or the Department of Health and Social Care. MP has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Servier. MW has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche, and Sandoz., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

This narrative review provides an overview of the current knowledge on health-related quality of life (HRQOL), a relevant clinical outcome in patients with epilepsy. It shows that the most important factor determining HRQOL in this patient group is seizure frequency. In particular, seizure-freedom is associated with better HRQOL scores. Many other factors may impact perceived HRQOL aspects, but their interrelation is complex and requires further research. Novel analytical approaches, such as hierarchical cluster and symptom network analyses might shed further light on this, and may result in recommendations for interventions on the most 'central' factors influencing different aspects of HRQOL in patients with epilepsy. Next, an overview of the HRQOL tools and analytical methods currently used in epilepsy care, with a focus on clinical trials, is provided. The QOLIE-31 is the most frequently applied and best validated tool. Several other questionnaires focusing on specific aspects of HRQOL (e.g., mood, social impact) are less frequently used. We show some pitfalls that should be taken into account when designing study protocols including HRQOL endpoints. This includes standardized statistical analysis approaches and predefined reporting methods for HRQOL in epilepsy populations. It has been shown in other patient groups that the lack of such standardisation negatively impacts the quality and comparability of results. We conclude with a number of recommendations for future research., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Glioblastoma patients are at high risk of developing venous thromboembolism (VTE). Tumor-intrinsic features are considered to play a role, but the underlying pathophysiological mechanisms remain incompletely understood., Objectives: To identify tumor-expressed genes and signaling pathways that associate with glioblastoma-related VTE by using next generation RNA-sequencing (RNA-Seq)., Methods: The tumor gene expression profile of 23 glioblastoma patients with VTE and 23 glioblastoma patients without VTE was compared using an unpaired analysis. Ingenuity Pathway Analysis (IPA) core analysis was performed on the top 50 differentially expressed genes to explore associated functions and pathways. Based on full RNA-Seq data, molecular glioblastoma subtypes were determined by performing cluster analysis., Results: Of the 19,327 genes, 1246 (6.4 %) were differentially expressed between glioblastoma patients with and without VTE (unadjusted P < 0.05). The most highly overexpressed gene was GLI1, a classical target gene in the Sonic Hedgehog (Shh) signaling pathway (log2 fold change: 3.7; unadjusted P < 0.0001, adjusted P = 0.219). In line, Shh signaling was among the top canonical pathways and processes associated with VTE. The proportion of patients with the proneural/neural glioblastoma subtype was higher among those with VTE than controls., Conclusion: Shh signaling may be involved in the development of glioblastoma-related VTE., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: F.A.K. has received research support from Bayer, BMS, BSCI, MSD, Leo Pharma, Actelion, Farm-X, The Netherlands Organization for Health Research and Development, The Dutch Thrombosis Foundation, The Dutch Heart Foundation and the Horizon Europe Program, all paid to his institution and outside the submitted work. The other authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: Leptomeningeal disease (LMD) is associated with poor survival and health-related quality of life (HRQoL). There is an urgent need for clinical research in this area to improve the outcomes. The purpose of this study is to summarize the areas of active clinical research in LMD, identify the knowledge gap, and suggest future research directions., Methods: A narrative review of clinical trials in LMD was conducted based on a search in clinicatrials.gov using the search term "leptomeningeal" under "condition or disease". Clinical trials in patients with LMD arising from solid malignancy that were labelled as "not yet recruiting", "recruiting", "enrolling by invitation" or "active, not recruiting" were included. Studies which were deemed to have significant impact on future research direction in LMD were selected for discussion., Key Content and Findings: A total of 38 clinical trials were included. Of these 38 trials, 19 are discussed in this review, with focus on their research questions and impact on future research directions. Most of the studies that were not selected for discussion focused on biomarker-driven interventions. Four key areas of research were identified, namely the (I) diagnosis, response assessment or molecular profiling of LMD (n=2); (II) advances in radiotherapy (n=3); (III) intrathecal treatment (n=13); (IV) novel drug carrier for systemic treatment (n=1). The research questions in the 19 discussed clinical trials included the tumour microenvironment of LMD, the role of novel molecular techniques in LMD, combination of radiotherapy with drugs, and cell-based immunotherapy. Among these 19 studies, 11 were phase 1 trials, 3 were phase 2 or phase 1/2 trials, 2 were phase 3 or phase 2/3 trials and the study phase was not reported in the remaining 3 studies. The existing knowledge gaps are discussed, including the lack of primary site-specific prognostic tools, cost-effectiveness studies, dedicated HRQoL assessment tools for LMD and sequencing of treatment., Conclusions: The current clinical trials in LMD offer the promise to improve the diagnosis and treatment outcomes of patients with LMD. More research is needed to overcome the potential hurdles in the current treatment and bridge the knowledge gaps as identified in this review, to improve patients' quantity and quality of survival.

Background: Distinguishing true tumor progression (TP) from treatment-induced abnormalities (eg, pseudo-progression (PP) after radiotherapy) on conventional MRI scans remains challenging in patients with a glioblastoma. We aimed to establish brain MRI phenotypes of glioblastomas early after treatment by combined analysis of structural and perfusion tumor characteristics and assessed the relation with recurrence rate and overall survival time., Methods: Structural and perfusion MR images of 67 patients at 3 months post-radiotherapy were visually scored by a neuroradiologist. In total 23 parameters were predefined and used for hierarchical clustering analysis. Progression status was assessed based on the clinical course of each patient 9 months after radiotherapy (or latest available). Multivariable Cox regression models were used to determine the association between the phenotypes, recurrence rate, and overall survival., Results: We established 4 subgroups with significantly different tumor MRI characteristics, representing distinct MRI phenotypes of glioblastomas: TP and PP rates did not differ significantly between subgroups. Regression analysis showed that patients in subgroup 1 (characterized by having mostly small and ellipsoid nodular enhancing lesions with some hyper-perfusion) had a significant association with increased mortality at 9 months (HR: 2.6 (CI: 1.1-6.3); P  = .03) with a median survival time of 13 months (compared to 22 months of subgroup 2)., Conclusions: Our study suggests that distinct MRI phenotypes of glioblastomas at 3 months post-radiotherapy can be indicative of overall survival, but does not aid in differentiating TP from PP. The early prognostic information our method provides might in the future be informative for prognostication of glioblastoma patients., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: The proportion of women among healthcare and biomedical research professionals in neuro-oncology is growing. With changes in cultural expectations and work-life balance considerations, more men aspire to nonfull-time jobs, yet, leadership positions remain dominated by men., Methods: The European Association of Neuro-Oncology (EANO) disparity committee carried out a digital survey to explore gender balance and actions suitable to promote gender equality. The survey was distributed among EANO members in 2021, with responses analyzed descriptively., Results: In total, 262 participants completed the survey (141 women, 53.8%; median age 43). Respondents were neurosurgeons (68, 26.0%); neurologists (67, 25.6%), medical oncologists (43, 16.4%), or other healthcare or research professionals; 208 participants (79.4%) worked full-time. Positive action to enforce the role of women in neuro-oncology was deemed necessary by 180 participants (68.7%), but only 28 participants (10.7%) agreed that women only should be promoted until gender balance is reached. A majority of respondents (162, 61.8%) felt that women with an equivalent CV should be prioritized over men to reach gender balance. If in the future the balance favored women at higher positions, 112 respondents (42.7%) agreed to apply positive action for men. The top indicators considered relevant to measure gender balance were: salary for similar positions (183/228, 80.3%), paid overtime (176/228, 77.2%), number of permanent positions (164/228, 71.9%), protected time for research (161/227, 70.9%), and training opportunities (157/227, 69.2%)., Conclusions: Specific indicators may help to measure and promote gender balance and should be considered for implementation among healthcare professionals in neuro-oncology., Competing Interests: E.L.R. reports personal financial interests as an advisory board member for Bayer, Janssen, Leo Pharma, Pierre Fabre, and Seattle Genetics; institutional funding from BMS. F.B. has no conflict of interest to declare. G.M. reports personal financial interests as an invited speaker for BrainLab and treasurer for the European Organisation for Research and Treatment of Cancer; institutional funding from AstraZeneca. N.G. has received honoraria for lectures from Blue Earth Diagnostics and for advisory board participation from Telix Pharmaceuticals. M.T. has no conflict of interest to declare. K.P. has no conflict of interest to declare. R.R. reports personal financial interests for advisory board membership for GENENTA, expert testimony for Novocure, and as an invited speaker for Bayer and UCB. Personal financial interests as an independent data monitoring committee member for Novocure, Servier, and CureVac. S.N. has no conflict of interest to declare. M.G. has no conflict of interest to declare. M.P. reports personal financial interests for advisory board membership for Abbvie, Adastra, AstraZeneca, Bayer, BMJ Journals, Bristol-Myers Squibb (BMS), CMC Contrast, Daiichi Sankyo, Gan & Lee Pharmaceuticals, Gerson Lehrman, GlaxoSmithKline (GSK), Lilly, Medahead, MedMedia, Merck Sharp & Dohme (MSD), Mundipharma, Novartis, Roche, Sanofi and Tocagen; institutional funding as coordinating principal investigator for PharmaMar and institutional research grants from Abbvie, Boehringer-Ingelheim, BMS, Daiichi Sankyo, GSK, MSD, Novocure and Roche. He reports non-financial interests as Past President of the European Association of Neuro-Oncology, Brain Tumor Group Chair for the European Organisation for Research and Treatment of Cancer, and as a member of the Multi-Site Guideline Advisory Group for the American Society of Clinical Oncology. M.W. reports personal financial interests as an advisory board member from Bayer, Curevac, Merck (EMD), Novartis, Novocure, and Philogen; personal financial interests as an independent data monitoring committee member for Orbus; institutional research grants from Quercis and Versameb. He also reports non-financial interests from a leadership role for the European Organisation for Research and Treatment of Cancer. S.C.S. received honoraria for lectures, advisory boards, or consultation from Bayer, Blue Earth, Tocagen, CeCaVa, and research grant funding from Apollomics. L.D. has no conflict of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Objectives: This review addresses the common problem of missing patient-reported outcome (PRO) data in clinical trials by assessing the current practice of their statistical handling as reported in publications of randomized controlled trials (RCTs) in patients with breast cancer., Study Design and Setting: We searched PubMed to identify RCTs evaluating biomedical treatments in breast cancer patients with at least one PRO endpoint published between January 2019 and February 2022. Two reviewers independently assessed the eligibility of the publications for this scoping review and extracted prespecified information on missing PRO data and related statistical practices., Results: Of 1,598 publications identified, 118 trials met the inclusion criteria. Eighty-eight (74.6%) trials reported the extent of missing data, with 11 (9.3%) not containing any missing PRO data. Twenty-one (19.6%) trials explicitly stated the statistical approach for handling missing data, with a preference for single imputation over multiple imputation approaches (57.2%/19.0%). Only six (5.6%) trials reported a sensitivity analysis to examine the extent to the results being affected by changes in assumptions made about missing PRO data., Conclusion: International efforts to raise awareness of the importance of accurately reporting state-of-the-art handling of missing PRO data are not yet fully reflected in the current literature of breast cancer RCTs., Competing Interests: Declaration of competing interest FE had a consultancy or advisory role for AbbVie, Incyte, Janssen, and Syros outside the submitted work. The other authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Routine assessment of patient-reported outcomes (PROs) in oncology has shown to improve the quality of the delivered care and to prolong survival. However, for successful implementation of routine assessment of PROs, more knowledge on their usability in clinical practice is needed., Objective: This study aimed to cross-sectionally assess the perspective of patients and clinicians on the practicality of routinely measuring PROs in clinical practice for glioma patients., Methods: Semistructured interviews were conducted evaluating the role of healthcare professionals (HCP) in discussing results of PRO measures (PROMs), and the preferred topics, methods and frequency of PRO assessment. Glioma patients, their proxies and HCPs involved in the treatment of glioma patients from eight centres in the Netherlands were included., Results: Twenty-four patients, 16 proxies and 35 HCPs were interviewed. The majority of patients, proxies and HCPs (92%, 81% and 80%, respectively) were willing to discuss PRO results during consultations. Although HCPs prefer that results are discussed with the nurse specialist, only one-third of patients/proxies agreed. Functioning of daily life was considered important in all three groups. Most participants indicated that discussion of PROM results should take place during standard follow-up visits, and completed at home about 1 week in advance. On group level, there was no preference for administration of questionnaires on paper or digitally. Lastly, all centres had staff available to send questionnaires on paper., Conclusion: This study shows that routine assessment of PROs is desired by patients, proxies and HCP's in neuro-oncological care in Dutch hospitals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023. The Author(s).)

Background: Glioma interventional studies should collect data aligned with patient priorities, enabling treatment benefit assessment and informed decision-making. This requires effective data synthesis and meta-analyses, underpinned by consistent trial outcome measurement, analysis, and reporting. Development of a core outcome set (COS) may contribute to a solution., Methods: A 5-stage process was used to develop a COS for glioma trials from the UK perspective. Outcome lists were generated in stages 1: a trial registry review and systematic review of qualitative studies and 2: interviews with glioma patients and caregivers. In stage 3, the outcome lists were de-duplicated with accessible terminology, in stage 4 outcomes were rated via a 2-round Delphi process, and stage 5 comprised a consensus meeting to finalize the COS. Patient-reportable COS outcomes were identified., Results: In Delphi round 1, 96 participants rated 35 outcomes identified in stages 1 and 2, to which a further 10 were added. Participants (77/96) rated the resulting 45 outcomes in round 2. Of these, 22 outcomes met a priori threshold for inclusion in the COS. After further review, a COS consisting of 19 outcomes grouped into 7 outcome domains (survival, adverse events, activities of daily living, health-related quality of life, seizure activity, cognitive function, and physical function) was finalized by 13 participants at the consensus meeting., Conclusions: A COS for glioma trials was developed, comprising 7 outcome domains. Additional research will identify appropriate measurement tools and further validate this COS., Competing Interests: RG: funding: NIHR, UCB Pharma. OLA: funding: NIHR Birmingham BRC, NIHR ARC WM, UKRI, Health Foundation, Janssen, Gilead, GlaxoSmithKline. Personal fees: Gilead Sciences, Merck, GlaxoSmithKline. LD: funding: Innovative Medicines Initiative, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group, Brain Tumour Charity. Neuro Oncology Journal Associate Editor. MC: Birmingham Health Partners Centre for Regulatory Science and Innovation and CPROR Director, NIHR senior investigator. Funding: NIHR, UKRI, NIHR Birmingham BRC, NIHR ARC WM, UK SPINE, European Regional Development Fund-Demand Hub and Health Data Research UK at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Innovate UK (part of UKRI), Macmillan Cancer Support, UCB Pharma, Janssen, GlaxoSmithKline, Gilead. Personal fees: Astellas, Aparito, CIS Oncology, Halfloop, Takeda, Merck, Daiichi Sankyo, Glaukos, GlaxoSmithKline, Patient-Centered Outcomes Research Institute. A relative owns GlaxoSmithKline shares., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Purpose: The purpose of this study is to develop a European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) questionnaire that captures the full range of physical, mental, and social health-related quality of life (HRQOL) issues relevant to disease-free cancer survivors. In this phase III study, we pretested the provisional core questionnaire (QLQ-SURV111) and aimed to identify essential and optional scales., Methods: We pretested the QLQ-SURV111 in 492 cancer survivors from 17 countries with one of 11 cancer diagnoses. We applied the EORTC QLG decision rules and employed factor analysis and item response theory (IRT) analysis to assess and, where necessary, modify the hypothesized questionnaire scales. We calculated correlations between the survivorship scales and the QLQ-C30 summary score and carried out a Delphi survey among healthcare professionals, patient representatives, and cancer researchers to distinguish between essential and optional scales., Results: Fifty-four percent of the sample was male, mean age was 60 years, and, on average, time since completion of treatment was 3.8 years. Eleven items were excluded, resulting in the QLQ-SURV100, with 12 functional and 9 symptom scales, a symptom checklist, 4 single items, and 10 conditional items. The essential survivorship scales consist of 73 items., Conclusions: The QLQ-SURV100 has been developed to assess comprehensively the HRQOL of disease-free cancer survivors. It includes essential and optional scales and will be validated further in an international phase IV study., Implications for Cancer Survivors: The availability of this questionnaire will facilitate a standardized and robust assessment of the HRQOL of disease-free cancer survivors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Early guidelines for minimally important differences (MIDs) for the EORTC QLQ-C30 proposed ≥10 points change as clinically meaningful for all scales. Increasing evidence that MIDs can vary by scale, direction of change, cancer type and estimation method has raised doubt about a single global standard. This paper identifies MID patterns for interpreting group-level change in EORTC QLQ-C30 scores across nine cancer types., Methods: Data were obtained from 21 published EORTC Phase III trials that enroled 13,015 patients across nine cancer types (brain, colorectal, advanced breast, head/neck, lung, mesothelioma, melanoma, ovarian, and prostate). Anchor-based MIDs for within-group change and between-group differences in change over time were obtained via mean change method and linear regression, respectively. Separate MIDs were estimated for improvements and deteriorations. Distribution-based estimates were derived and compared with anchor-based MIDs., Results: Anchor-based MIDs mostly ranged from 5 to 10 points. Differences in MIDs for improvement vs deterioration, for both within-group and between-group, were mostly within a 2-points range. Larger differences between within-group and between-group MIDs were observed for several scales in ovarian, lung and head/neck cancer. Most anchor-based MIDs ranged between 0.3 SD and 0.5 SD distribution-based estimates., Conclusions: Our results reinforce recent claims that no single MID can be applied to all EORTC QLQ-C30 scales and disease settings. MIDs varied by scale, improvement/deterioration, within/between comparisons and by cancer type. Researchers applying commonly used rules of thumb must be aware of the risk of dismissing changes that are clinically meaningful or underpowering analyses when smaller MIDs apply., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of interests SR is a current employee of Pfizer and a former employee of Novartis Pharma. JC, PC, and JR are current employees of Pfizer. VP and IG are current employees of EMD Serono. MS is a current employee of Merk. GV has received consulting fees or payment from or related to the following organisations: Pfizer, Eisai, Roche, Novartis, AstraZeneca, Sanofi, Seattle Genetics, the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group, and the EORTC Board. KO's organisation has received sponsorship funding or grants for various annual programmes and activities from Bristol Myers Squibb, Novocure, Pfizer, Bayer, Novartis, Northwest Biotherapeutics, Karyopharm, MagForce, Medac, Photonamic, Apogenix, Elekta, and GW Pharmaceuticals/Jazz Pharmaceuticals; consulting fees from Bristol Myers Squibb and Novartis; and honoraria from Sanofi, Sharing Progress in Cancer Care, and Seagen. KO participated in an advisory board for Novartis, Novocure, Seagen, Eisai, Bristol Myers Squibb, and Sanofi, and has leadership roles in a number of organisations. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Patients' reduced awareness of neurocognitive functioning (NCF) may negatively affect the reliability of patient-reported outcomes (PROs) and clinical decision-making. This study evaluated cognitive awareness, defined as the association between NCF and neurocognitive complaints, over the disease course of patients with recurrent high-grade glioma (HGG)., Methods: We assessed NCF using the EORTC core clinical trial battery and neurocognitive complaints using the Medical Outcome Study questionnaire. Patients were categorised as impaired or intact, based on their neurocognitive performance. Spearman's rank correlations were calculated between NCF and neurocognitive complaints at baseline and each 12 weeks, until 36. The association between changes in NCF and neurocognitive complaints scores between these follow-up assessments was determined using Pearson's correlation., Results: A total of 546 patients were included. Neurocognitively impaired patients (n = 437) had more neurocognitive complaints (range: 10.51 [p < 0.001] to 13.34 [p = 0.001]) than intact patients (n = 109) at baseline, at 12 and 24 weeks. In intact patients, NCF and neurocognitive complaints were correlated for only one domain at baseline (0.202, p = 0.036), while in impaired patients correlations were more frequently found in various domains and time points (range: 0.164 [p = 0.001] to 0.334 [p = 0.011]). Over the disease course, NCF and neurocognitive complaints were correlated for only one domain at baseline (0.357, p = 0.014) in intact patients while in impaired patients they were correlated for more domains and time points (range: 0.222 [p < 0.001] to 0.366 [p < 0.001])., Conclusion: Neurocognitively impaired patients with recurrent HGG are aware of their neurocognitive limitations at study entry and during follow-up, which should be considered in clinical decision-making and when interpreting PRO results., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Fatigue is a commonly reported and severe symptom in primary brain tumor patients, but the exact occurrence in meningioma patients is unknown. This study aimed to determine the frequency and severity of fatigue in meningioma patients as well as associations between the level of fatigue and patient-, tumor-, and treatment-related factors., Methods: In this multicenter cross-sectional study, meningioma patients completed questionnaires on fatigue (MFI-20), sleep (PSQI), anxiety and depression (HADS), tumor-related symptoms (MDASI-BT), and cognitive functioning (MOS-CFS). Multivariable regression models were used to evaluate the independent association between fatigue and each patient-, tumor-, and treatment-related factor separately, corrected for relevant confounders., Results: Based on predetermined in- and exclusion criteria, 275 patients, on average 5.3 (SD = 2.0) year since diagnosis, were recruited. Most patients had undergone resection (92%). Meningioma patients reported higher scores on all fatigue subscales compared to normative data and 26% were classified as fatigued. Having experienced a complication due to resection (OR 3.6, 95% CI: 1.8-7.0), having received radiotherapy (OR 2.4, 95% CI: 1.2-4.8), a higher number of comorbidities (OR 1.6, 95% CI: 1.3-1.9) and lower educational level (low level as reference; high level OR 0.3, 95% CI: 0.2-0.7) were independently associated with more fatigue., Conclusions: Fatigue is a frequent problem in meningioma patients even many years after treatment. Both patient- and treatment-related factors were determinants of fatigue, with the treatment-related factors being the most likely target for intervention in this patient population., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)