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Background: Patients with glioblastoma have a poor prognosis and treatment is palliative in nature from diagnosis. It is therefore critical that the benefits and burdens of treatments are clearly discussed with patients and caregivers. Aim: To explore experiences and preferences around glioblastoma treatment communication in patients, family caregivers and healthcare professionals. Design: Qualitative design. A thematic analysis of semi-structured interviews. Setting/participants: A total of 15 adult patients with glioblastoma, 13 caregivers and 5 healthcare professionals were recruited from Leeds Teaching Hospitals NHS Trust. Results: Four themes were identified: (1) Communication practice and preferences. Risks and side-effects of anti-tumour treatments were explained clearly, with information layered and repeated. Treatment was often understood to be ‘the only option’. Understanding the impact of side-effects could be enhanced, alongside information about support services. (2) What matters most. Patients/caregivers valued being well-supported by a trusted treatment team, feeling involved, having control and quality of life. Healthcare professionals similarly highlighted trust, maintaining independence and emotional support as key. (3) Decision-making. With limited treatment options, trust and control are crucial in decision-making. Patients ultimately prefer to follow healthcare professional advice but want to be involved, consider alternatives and voice what matters to them. (4) Impact of COVID-19. During the pandemic, greater efforts to maintain good communication were necessary. Negative impacts of COVID-19 were limited, caregivers appeared most disadvantaged by pandemic-related restrictions. Conclusions: In glioblastoma treatment communication, where prognosis is poor and treatmentwill not result in cure, building trusting relationships, maintaining a sense of control and being well-informed are identified as critical.

Peer reviewed: True, INTRODUCTION: Primary brain tumours, specifically gliomas, are a rare disease group. The disease and treatment negatively impacts on patients and those close to them. The high rates of physical and cognitive morbidity differ from other cancers causing reduced health-related quality of life. Glioma trials using outcomes that allow holistic analysis of treatment benefits and risks enable informed care decisions. Currently, outcome assessment in glioma trials is inconsistent, hindering evidence synthesis. A core outcome set (COS) - an agreed minimum set of outcomes to be measured and reported - may address this. International initiatives focus on defining core outcomes assessments across brain tumour types. This protocol describes the development of a COS involving UK stakeholders for use in glioma trials, applicable across glioma types, with provision to identify subsets as required. Due to stakeholder interest in data reported from the patient perspective, outcomes from the COS that can be patient-reported will be identified. METHODS AND ANALYSIS: Stage I: (1) trial registry review to identify outcomes collected in glioma trials and (2) systematic review of qualitative literature exploring glioma patient and key stakeholder research priorities. Stage II: semi-structured interviews with glioma patients and caregivers. Outcome lists will be generated from stages I and II. Stage III: study team will remove duplicate items from the outcome lists and ensure accessible terminology for inclusion in the Delphi survey. Stage IV: a two-round Delphi process whereby the outcomes will be rated by key stakeholders. Stage V: a consensus meeting where participants will finalise the COS. The study team will identify the COS outcomes that can be patient-reported. Further research is needed to match patient-reported outcomes to available measures. ETHICS AND DISSEMINATION: Ethical approval was obtained (REF SMREC 21/59, Cardiff University School of Medicine Research Ethics Committee). Study findings will be disseminated widely through conferences and journal publication. The final COS will be adopted and promoted by patient and carer groups and its use by funders encouraged. PROSPERO REGISTRATION NUMBER: CRD42021236979.

IntroductionGliomas are the most common primary tumour of the central nervous system (CNS), with an estimated annual incidence of 6.6 per 100 000 individuals in the USA and around 14 deaths per day from brain tumours in the UK. The genomic and biological landscape of brain tumours has been increasingly defined and, since 2016, the WHO classification of tumours of the CNS incorporates molecular data, along with morphology, to define tumour subtypes more accurately. The Tessa Jowell BRAIN MATRIX Platform (TJBM) study aims to create a transformative clinical research infrastructure that leverages UK National Health Service resources to support research that is patient centric and attractive to both academic and commercial investors.Methods and analysisThe TJBM study is a programme of work with the principal purpose to improve the knowledge of glioma and treatment for patients with glioma. The programme includes a platform study and subsequent interventional clinical trials (as separate protocols). The platform study described here is the backbone data-repository of disease, treatment and outcome data from clinical, imaging and pathology data being collected in patients with glioma from secondary care hospitals. The primary outcome measure of the platform is time from biopsy to integrated histological–molecular diagnosis using whole-genome sequencing and epigenomic classification. Secondary outcome measures include those that are process centred, patient centred and framework based. Target recruitment for the study is 1000 patients with interim analyses at 100 and 500 patients.Ethics and disseminationThe study will be performed in accordance with the recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Association General Assembly, Helsinki, Finland and stated in the respective participating countries’ laws governing human research, and Good Clinical Practice. The protocol was initially approved on 18 February 2020 by West Midlands – Edgbaston Research Ethics Committee; the current protocol (v3.0) was approved on 15 June 2022. Participants will be required to provide written informed consent. A meeting will be held after the end of the study to allow discussion of the main results among the collaborators prior to publication. The results of this study will be disseminated through national and international presentations and peer-reviewed publications. Manuscripts will be prepared by the Study Management Group and authorship will be determined by mutual agreement.Trial registration numberNCT04274283, 18-Feb-2020;ISRCTN14218060, 03-Feb-2020.

Core Outcome Sets (COS) define minimum outcomes to be measured and reported in clinical effectiveness trials for a particular health condition/health area. Despite recognition as critical to clinical research design for other health areas, none have been developed for neuro-oncology. COS development projects should carefully consider: scope (how the COS should be used), stakeholders involved in development (including patients as both research partners and participants), and consensus methodologies used (typically a Delphi survey and consensus meeting), as well as dissemination plans. Developing COS for neuro-oncology is potentially challenging due to extensive tumor subclassification (including molecular stratification), different symptoms related to anatomical tumor location, and variation in treatment options. Development of a COS specific to tumor subtype, in a specific location, for a particular intervention may be too narrow and would be unlikely to be used. Equally, a COS that is applicable across a wider area of neuro-oncology may be too broad and therefore lack specificity. This review describes why and how a COS may be developed, and discusses challenges for their development, specific to neuro-oncology. The COS under development are briefly described, including: adult glioma, incidental/untreated meningioma, meningioma requiring intervention, and adverse events from surgical intervention for pediatric brain tumors.

IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two ‘Core Outcome Sets’ (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration numberCOMET study ID 1508

Background The Response Assessment in Neuro-Oncology Patient-Reported Outcome (RANO-PRO) working group aims to provide guidance on the use of PROs in brain tumor patients. PRO measures should be of high quality, both in terms of relevance and other measurement properties. This systematic review aimed to identify PRO measures that have been used in brain tumor studies to date. Methods A systematic literature search for articles published up to June 25, 2020 was conducted in several electronic databases. Pre-specified inclusion criteria were used to identify studies using PRO measures assessing symptoms, (instrumental) activities of daily living [(I)ADL] or health-related quality of life (HRQoL) in adult patients with glioma, meningioma, primary central nervous system lymphoma, or brain metastasis. Results A total of 215 different PRO measures were identified in 571 published and 194 unpublished studies. The identified PRO measures include brain tumor-specific, cancer-specific, and generic instruments, as well as instruments designed for other indications or multi- or single-item study-specific questionnaires. The most frequently used instruments were the EORTC QLQ-C30 and QLQ-BN20 (n = 286 and n = 247), and the FACT-Br (n = 167), however, the majority of the instruments were used only once or twice (150/215). Conclusion Many different PRO measures assessing symptoms, (I)ADL or HRQoL have been used in brain tumor studies to date. Future research should clarify whether these instruments or their scales/items exhibit good content validity and other measurement properties for use in brain tumor patients.

AIMS Trial registration supports unbiased reporting of research studies. Despite inconsistent use globally and sub-optimal completeness, registration is associated with publication of the same outcomes as defined in trial protocols, though these are not necessarily reported in published results. In the core outcomes in brain tumour trials (COBra) study a registry review was undertaken, alongside a systematic review of qualitative literature and semi-structured interviews, to develop a core outcome set (COS) outcome longlist. The study aims to identify all outcomes reported across all glioma trial registration data. METHOD Phase 3 interventional glioma trials involving patients aged 18 and over, registered on clinicaltrials.gov or the ISRCTN registry were included. Two researchers independently searched the databases and registered data and available protocols were retrieved. Two reviewers independently extracted basic trial data including primary and secondary outcomes. Outcomes were categorised according to an ontology developed through literature review. RESULTS 91 trials were identified. Primary outcome categories reported were survival (84%), disease activity (14%), symptoms (4%), adverse events (3%) and resource use (1%). Secondary outcome categories reported were survival (60%), adverse events (52%), quality of life (QoL, 41%), disease activity (30%), symptoms (20%), function (12%), resource use (7%), health status (7%), and economic (3%). The review contributed 15 unique outcomes to the final outcome longlist of 35. CONCLUSION Trial registries represent a pragmatic solution in COS development and enabled identification of outcomes not present in other data sources. Under half of registered glioma studies included QoL outcomes; a small minority included functional outcomes or economic evaluation.

AIMS To understand the current levels of Allied Health Professional (AHP) provision within adult neuro-oncology in the UK, gain insight into perceived gaps and any impact of the COVID-19 pandemic on this provision, from the Health Care Professional’s (HCP) perspective. METHOD In collaboration with brainstrust (a brain tumour charity) and the author, a mixed-methods, on-line survey of HCPs working within adult neuro-oncology was designed, tested and distributed to HCPs registered on the charity’s HCP database. Quantitative data was analysed using simple descriptive statistics. Qualitative data was analysed using thematic analysis. RESULTS 51 HCPs from multiple roles and teams across the UK responded. 66% (34) reported a service delivery gap, including a lack of specialist AHP support, with high geographical variability. During the COVID-19 pandemic, 60.8% (31) respondents identified a reduction in access to AHP support. 58.8% (30) respondents reported a change in appointment modality, with an increase in telephone and video appointments and a decrease in face-to-face appointments and home visits. This modality change was highlighted as a possible cause of reduced HCP awareness of symptom progression that was also reported. CONCLUSION There is paucity of data regarding AHP provision within adult neuro-oncology and the impact of the COVID-19 pandemic on this provision. This study highlights concerns regarding overall specialist AHP support which reduced further during the COVID-19 pandemic. The impact on patients is unknown and highlights a need for further research to inform development of national guidelines for specialist AHP provision and the use of telehealth for this complex patient group.

AIMS Glioma, the most common primary brain tumour, has variable survival rates. Existing evidence describes detriment to quality of life from persistent symptoms/side effects, functional loss and feelings of disconnection, particularly in glioblastoma; however, there remains limited focus on the experience of longer-term survivors. This study aimed to ascertain the lived experience of people with glioma and their caregivers, part of a larger study identifying outcomes for a core outcome set for use in glioma trials (COBra study). METHOD Semi-structured interviews with UK glioma patients, or patient-caregiver dyads, analysed using Thematic Analysis. RESULTS Nineteen interviews were undertaken. Patients and caregivers described living with uncertainty long after diagnosis and treatment, including prognostic uncertainty and anxiety surrounding recurrence and worsening symptoms. Patients described an inability to plan long-term, struggling to return to normal activities, either due to progressive tumour symptoms, and/or treatment side effects. Long-term physical and psychological side effects were highly impactful; patients felt left alone to cope, with support following treatment dropping off rapidly. Patients/caregivers sought self-directed ways to cope, focusing on routine and achieving some normality. However, the physical and neurological effects of glioma and its treatment affected all aspects of daily life and social interactions, impacting on sense of wellbeing and quality of life. CONCLUSION People with glioma, and their caregivers, struggle with loss of normality and living with uncertainty long after diagnosis. They proactively engage in self-directed approaches towards mitigating these effects, but experience gaps in support after treatment finishes. Clinical follow up should target these aspects of assessment and intervention.

ObjectivesTo assess whether recommendations of individually oriented lifestyle interventions (IOLIs) in guidelines from the National Institute for Health and Care Excellence (NICE) were underpinned by evidence of benefit, and whether harms and opportunity costs were considered.DesignCross sectional survey.SettingUK.Data sourcesNICE guidelines and supporting evidence.Eligibility criteriaAll NICE pathways for IOLI recommendations (ie, non-drug interventions that healthcare professionals administer to adults to achieve a healthier lifestyle and improve health) were searched systematically on 26 August 2020. One author screened all retrieved pathways for candidate guidelines, while a second author verified these judgments. Two authors independently and in duplicate screened all retrieved guidelines and recommendations for eligibility, extracted data, and evaluated the evidence cited and the outcomes considered. Disagreements were noted and resolved by consensus.ResultsWithin 57 guidelines, 379 NICE recommendations were found for IOLIs; almost all (n=374; 99%) recommended the lifestyle intervention and five (1%) recommended against the intervention. Of the 379 recommendations, 13 (3%) were supported by moderate or high certainty evidence of a beneficial effect on patient relevant outcomes (n=7; 2%) or surrogate outcomes (n=13; 3%). 19 (5%) interventions considered psychosocial harms, 32 (8%) considered physical harms, and one (ConclusionFew NICE recommendations of lifestyle interventions are supported by reliable evidence. While this finding does not contest the beneficial effects of healthy habits, guidelines recommending clinicians to try to change people’s lifestyle need to be reconsidered given the substantial uncertainty about the effectiveness, harms, and opportunity costs of such interventions.

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 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.

Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumor, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs; however, this ambition remains to be realized. In view of this lack of progress, the FDA–AACR–ASTRO Clinical Development of Drug–Radiotherapy Combinations Workshop was held in February 2018 to bring together stakeholders and opinion leaders from academia, clinical radiation oncology, industry, patient advocacy groups, and the FDA to discuss challenges to introducing new drug–radiotherapy combinations to the clinic. This Perspectives in Regulatory Science and Policy article summarizes the themes and action points that were discussed. Intelligent trial design is required to increase the number of studies that efficiently meet their primary outcomes; endpoints to be considered include local control, organ preservation, and patient-reported outcomes. Novel approaches including immune-oncology or DNA-repair inhibitor agents combined with radiotherapy should be prioritized. In this article, we focus on how the regulatory challenges associated with defining a new drug–radiotherapy combination can be overcome to improve clinical outcomes for patients with cancer.

Objective The aim of this study was to determine the experience of patients with brain tumors and their carers across distinct parts of their treatment pathway and identify their views on potential service gaps in need of addressing. Methods A structured survey was administered at patient workshops across the UK and online through a charity newsletter. Answers to closed questions were analyzed using descriptive statistics, and open questions were examined using techniques of inductive content analysis. Results A total of 136 survey responses were received, representing patients with a variety of diagnoses and geographical locations (30 counties). There was a wide range of opinions on the provision of current neuro-oncology services. Key themes identified included a perceived lack of information provision, a gap in postdischarge psychological and neuropsychological supports, and an unmet willingness for involvement in research. Conclusion This national survey enhances our knowledge of current patient and carer experience within neuro-oncology services. A number of areas of unmet clinical need are highlighted providing a basis for informing future patient-centered service improvements and research.

BackgroundTrials of approved medications for new indications are becoming increasingly common (repurposing). SPRING – Seizure Prophylaxis IN Glioma is a trial of prophylactic Levetiracetam in adults without prior history of seizure versus no AED. Significant delays were encountered in the set up phase.IssuesLegal contracts between Sponsor and NIHR/UCB (£1.76m) were prolonged.UCB (Belgium) would only transfer drug when ethics had been granted and BREXIT loomed. Company to package levetiracetam required national procurement exercise.Conflicting IRAS advice (Ireland, Scotland, England). Inclusion criteria included patients must have capacity. As patients could lose capacity during study this required Adults with Incapacity REC (Essex), secondary review in Scotland and screening for capacity at each visit. MHRA – mandated monitoring for suicidal ideation at each visit, and detail on contraception during study. HRA – suggested changes to the Patient Information Leaflet and a Schedule of Events Cost Attribution Template – requiring multiple substantial amendments.Neurosurgical centres may feed several oncological departments - site contracts are complex. Electronic eCRF takes time to build and test.ConclusionsConsider planning for longer set up phase in grant submissions. Views expressed are those of the author(s) and not necessarily those of the NHS, NIHR or DOHSC.robin.grant@luht.scot.nhs.uk

Multiple studies have identified the prognostic relevance of extent of resection in the management of glioma. Different intraoperative technologies have emerged in recent years with unknown comparative efficacy in optimising extent of resection. One previous Cochrane Review provided low- to very low-certainty evidence in single trial analyses and synthesis of results was not possible. The role of intraoperative technology in maximising extent of resection remains uncertain. Due to the multiple complementary technologies available, this research question is amenable to a network meta-analysis methodological approach.To establish the comparative effectiveness and risk profile of specific intraoperative imaging technologies using a network meta-analysis and to identify cost analyses and economic evaluations as part of a brief economic commentary.We searched CENTRAL (2020, Issue 5), MEDLINE via Ovid to May week 2 2020, and Embase via Ovid to 2020 week 20. We performed backward searching of all identified studies. We handsearched two journals, Neuro-oncology and the Journal of Neuro-oncology from 1990 to 2019 including all conference abstracts. Finally, we contacted recognised experts in neuro-oncology to identify any additional eligible studies and acquire information on ongoing randomised controlled trials (RCTs).RCTs evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included fluorescence-guided surgery, intraoperative ultrasound, neuronavigation (with or without additional image processing, e.g. tractography), and intraoperative MRI.Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma.We identified four RCTs, using different intraoperative imaging technologies: intraoperative magnetic resonance imaging (iMRI) (2 trials, with 58 and 14 participants); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around winter 2020. We identified no published trials for intraoperative ultrasound. Network meta-analyses or traditional meta-analyses were not appropriate due to absence of homogeneous trials across imaging technologies. Of the included trials, there was notable heterogeneity in tumour location and imaging technologies utilised in control arms. There were significant concerns regarding risk of bias in all the included studies. One trial of iMRI found increased extent of resection (risk ratio (RR) for incomplete resection was 0.13, 95% confidence interval (CI) 0.02 to 0.96; 49 participants; very low-certainty evidence) and one trial of 5-ALA (RR for incomplete resection was 0.55, 95% CI 0.42 to 0.71; 270 participants; low-certainty evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants; therefore, the trial provided very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection. Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-certainty evidence). Overall, the proportion of reported events was low in most trials and, therefore, issues with power to detect differences in outcomes that may or may not have been present. Survival outcomes were not adequately reported, although one trial reported no evidence of improvement in overall survival with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07; 270 participants; low-certainty evidence). Data for quality of life were only available for one study and there was significant attrition bias (very low-certainty evidence).Intraoperative imaging technologies, specifically 5-ALA and iMRI, may be of benefit in maximising extent of resection in participants with high-grade glioma. However, this is based on low- to very low-certainty evidence. Therefore, the short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. Network and traditional meta-analyses were not possible due to the identified high risk of bias, heterogeneity, and small trials included in this review. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, one non-systematic review of economic studies suggested that, compared with standard surgery, use of image-guided surgery has an uncertain effect on costs and that 5-ALA was more costly. Further research, including completion of ongoing trials of ultrasound-guided surgery, is needed.En múltiples estudios se ha identificado la importancia pronóstica del alcance de la resección en el tratamiento del glioma. En los últimos años han surgido diferentes tecnologías intraoperatorias con una eficacia comparativa desconocida para optimizar el alcance de la resección. Una revisión Cochrane anterior proporcionó evidencia de certeza baja a muy baja en los análisis de un solo ensayo y no fue posible la síntesis de los resultados. La función de la tecnología intraoperatoria para maximizar el alcance de la resección aún no está clara. Debido a las múltiples tecnologías complementarias disponibles, esta pregunta de investigación se presta a un enfoque metodológico de metanálisis en red.Establecer el perfil comparativo de efectividad y riesgo de determinadas tecnologías de imagenología intraoperatorias mediante un metanálisis en red e identificar análisis de costos y evaluaciones económicas como parte de un breve comentario económico. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en CENTRAL (2020, número 5), MEDLINE vía Ovid hasta la semana 2 de mayo de 2020, y Embase vía Ovid hasta la semana 20 de 2020. Se realizó una búsqueda retrospectiva de todos los estudios identificados. Se hicieron búsquedas manuales en dos revistas, Neuro‐oncology y Journal of Neuro‐oncology, desde 1990 hasta 2019, y se incluyeron todos los resúmenes de congresos. Finalmente, se estableció contacto con expertos reconocidos en neurooncología para identificar cualquier estudio elegible adicional y obtener información sobre los ensayos controlados aleatorizados (ECA) en curso. CRITERIOS DE SELECCIÓN: ECA que evaluaron a personas de todas las edades con presuntos tumores gliales nuevos o recidivantes (de cualquier ubicación o histología) a partir del examen clínico y la imagenología (tomografía computarizada [TC] o imagenología de resonancia magnética [IRM], o ambas). Las modalidades adicionales de imagenología (p.ej., tomografía de emisión de positrones, espectroscopia de resonancia magnética) no fueron obligatorias. Las intervenciones incluyeron cirugía guiada por fluorescencia, ecografía intraoperatoria, neuronavegación (con o sin procesamiento adicional de las imágenes, p.ej., tractografía) e IRM intraoperatoria. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron los resultados de la búsqueda en cuanto a su relevancia, realizaron la evaluación crítica según las guías conocidas y extrajeron los datos mediante un formulario predeterminado.Se identificaron cuatro ECA, que utilizaron diferentes tecnologías de imagenología intraoperatorias: la resonancia magnética (IRM) intraoperatoria (dos ensayos, con 58 y 14 participantes); la cirugía guiada por fluorescencia con ácido 5‐aminolevulínico (5‐ALA) (un ensayo, 322 participantes); y la neuronavegación (un ensayo, 45 participantes). Se identificó un ensayo en curso que evaluó la IRM con un tamaño de la muestra planificado de 304 participantes, del que se espera la publicación de los resultados alrededor del invierno de 2020. No se han identificado ensayos publicados sobre la ecografía intraoperatoria. Los metanálisis en red o los metanálisis tradicionales no fueron apropiados debido a la falta de ensayos homogéneos en tecnologías de imagenología. De los ensayos incluidos, hubo una notable heterogeneidad en la localización de los tumores y en las tecnologías de imagenología utilizadas en los brazos control. Hubo inquietudes significativas con respecto al riesgo de sesgo en todos los estudios incluidos. Un ensayo de IRM encontró un aumento en la extensión de la resección (razón de riesgos [RR] para la resección incompleta 0,13; intervalo de confianza [IC] del 95%: 0,02 a 0,96; 49 participantes; evidencia de certeza muy baja) y un ensayo de 5‐ALA (RR para la resección incompleta 0,55; IC del 95%: 0,42 a 0,71; 270 participantes; evidencia de certeza baja). El otro ensayo que evaluó la IRM se interrumpió de forma temprana después de un análisis intermedio no planificado que incluyó 14 participantes; por lo tanto, el ensayo proporciona evidencia de calidad muy baja. El ensayo de neuronavegación no proporcionó datos suficientes para evaluar los efectos sobre el grado de resección. El informe de los eventos adversos fue incompleto e indicó la presencia de sesgo de informe significativo (evidencia de certeza muy baja). En general, la proporción de eventos informados fue baja en la mayoría de los ensayos y, por lo tanto, pueden haber estado presentes o no problemas relacionados con el poder estadístico suficiente para detectar diferencias en los desenlaces. No se informó adecuadamente sobre los desenlaces de supervivencia, aunque un ensayo no informó evidencia de mejora en la supervivencia general con 5‐ALA (cociente de riesgos instantáneos [CRI] 0,82; IC del 95%: 0,62 a 1,07; 270 participantes; evidencia de certeza baja). Solo hubo datos disponibles sobre la calidad de vida de un estudio, con un sesgo de desgaste significativo (evidencia de certeza muy baja).Las tecnologías de imagenología intraoperatoria, específicamente la IRM y el 5‐ALA, pueden ser beneficiosas para maximizar el grado de resección en los participantes con glioma de grado alto. Sin embargo, lo anterior se basa en evidencia de certeza baja a muy baja. Por lo tanto, los efectos neurológicos a corto y a largo plazo no están claros. No están claros los efectos de la cirugía guiada por imágenes sobre la supervivencia general, la supervivencia sin progresión ni la calidad de vida. No fue posible realizar metanálisis en red ni tradicionales debido al alto riesgo de sesgo identificado, a la heterogeneidad y a los ensayos pequeños incluidos en esta revisión. Un comentario económico breve encontró evidencia económica limitada sobre el uso equívoco de la IRM en comparación con la cirugía convencional. En cuanto a los costos, una revisión no sistemática de estudios económicos indicó que, en comparación con la cirugía estándar, el uso de la cirugía guiada por imágenes no tiene un efecto claro sobre los costos y que el ácido 5‐aminolevulínico fue más costoso. Se necesitan estudios de investigación adicionales, incluida la finalización de los ensayos en curso sobre la cirugía guiada por ecografía.

Background Brain tumor patients are at high risk of impaired medical decision-making capacity (MDC), which can be ethically challenging because it limits their ability to give informed consent to medical treatments or participation in research. The European Association of Neuro-Oncology Palliative Care Multidisciplinary Task Force performed a systematic review to identify relevant evidence with respect to MDC that could be used to give recommendations on how to cope with reduced MDC in brain tumor patients. Methods A literature search in several electronic databases was conducted up to September 2019, including studies with brain tumor and other neurological patients. Information related to the following topics was extracted: tools to measure MDC, consent to treatment or research, predictive patient- and treatment-related factors, surrogate decision making, and interventions to improve MDC. Results A total of 138 articles were deemed eligible. Several structured capacity-assessment instruments are available to aid clinical decision making. These instruments revealed a high incidence of impaired MDC both in brain tumors and other neurological diseases for treatment- and research-related decisions. Incapacity appeared to be mostly determined by the level of cognitive impairment. Surrogate decision making should be considered in case a patient lacks capacity, ensuring that the patient’s “best interests” and wishes are guaranteed. Several methods are available that may help to enhance patients’ consent capacity. Conclusions Clinical recommendations on how to detect and manage reduced MDC in brain tumor patients were formulated, reflecting among others the timing of MDC assessments, methods to enhance patients’ consent capacity, and alternative procedures, including surrogate consent.

BACKGROUND Meningioma is the commonest primary brain tumour. 70% of patients are seizure-free at presentation, but approximately 12% will have seizures within 12 months of surgery. Seizures impact quality of life. Neurosurgeons administer prophylactic anti-epileptic drugs (AED) to prevent seizures despite a lack of evidence to support this. A meta-analysis of RCTs in brain tumours suggests that older AED may prevent seizures in the first week after surgery but not thereafter. There are no studies assessing newer AEDs in the prophylactic setting. RESEARCH QUESTION In patients with meningioma who have never had a seizure and are undergoing surgical resection, does prophylactic levetiracetam reduce the risk of developing seizures? DESIGN multi-centre, double-blind RCT in 20 UK centres. 1:1 randomisation of 14 days levetiracetam 500mg bd started one day before surgery compared to placebo. PRIMARY OBJECTIVE Determine whether 2 weeks prophylactic levetiracetam reduces the risk of developing seizures within 12 months of surgery compared to placebo. ECONOMIC OBJECTIVE Estimate cost-effectiveness of prophylactic levetiracetam. SECONDARY OBJECTIVES Determine effect of prophylaxis on time to first seizure and first convulsive seizure, whether prophylaxis affects quality of life and influences return to driving, safety of prophylaxis. POPULATION seizure-naïve meningioma undergoing surgery. SAMPLE SIZE seizure rate at 12 months is 12.3%. A 50% reduction is clinically beneficial. A two-group chi-squared test with 5% two-sided significance level will have 90% power to detect the difference between a Group 1 proportion of 0.12 and a Group 2 proportion of 0.06 when the sample size in each group is 477. Allowing for 5% dropout, 1004 patients will be recruited. FUNDING NIHR (£1.64M) award June 2020. Study opens March 2021. TRANSLATIONAL RESEARCH MRI, blood and tissue will be collected to explore risk factors for seizures. CONCLUSIONS study will provide class I evidence of the role of prophylactic levetiracetam in meningioma surgery.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To establish the comparative effectiveness and risk profile of specific intraoperative imaging technologies using a network meta‐analysis.

BACKGROUND: Brain tumours are recognised as one of the most difficult cancers to diagnose because presenting symptoms, such as headache, cognitive symptoms, and seizures, may be more commonly attributable to other, more benign conditions. Interventions to reduce the time to diagnosis of brain tumours include national awareness initiatives, expedited pathways, and protocols to diagnose brain tumours, based on a person's presenting symptoms and signs; and interventions to reduce waiting times for brain imaging pathways. If such interventions reduce the time to diagnosis, it may make it less likely that people experience clinical deterioration, and different treatment options may be available.OBJECTIVES: To systematically evaluate evidence on the effectiveness of interventions that may influence: symptomatic participants to present early (shortening the patient interval), thresholds for primary care referral (shortening the primary care interval), and time to imaging diagnosis (shortening the secondary care interval and diagnostic interval). To produce a brief economic commentary, summarising the economic evaluations relevant to these interventions.SEARCH METHODS: For evidence on effectiveness, we searched CENTRAL, MEDLINE, and Embase from January 2000 to January 2020; Clinicaltrials.gov to May 2020, and conference proceedings from 2014 to 2018. For economic evidence, we searched the UK National Health Services Economic Evaluation Database from 2000 to December 2014.SELECTION CRITERIA: We planned to include studies evaluating any active intervention that may influence the diagnostic pathway, e.g. clinical guidelines, direct access imaging, public health campaigns, educational initiatives, and other interventions that might lead to early identification of primary brain tumours. We planned to include randomised and non-randomised comparative studies. Included studies would include people of any age, with a presentation that might suggest a brain tumour.DATA COLLECTION AND ANALYSIS: Two review authors independently assessed titles identified by the search strategy, and the full texts of potentially eligible studies. We resolved discrepancies through discussion or, if required, by consulting another review author.MAIN RESULTS: We did not identify any studies for inclusion in this review. We excluded 115 studies. The main reason for exclusion of potentially eligible intervention studies was their study design, due to a lack of control groups. We found no economic evidence to inform a brief economic commentary on this topic.AUTHORS' CONCLUSIONS: In this version of the review, we did not identify any studies that met the review inclusion criteria for either effectiveness or cost-effectiveness. Therefore, there is no evidence from good quality studies on the best strategies to reduce the time to diagnosis of brain tumours, despite the prioritisation of research on early diagnosis by the James Lind Alliance in 2015. This review highlights the need for research in this area.

Background:\ud A glioblastoma is a fatal type of brain tumour for which the standard of care is maximum surgical resection followed by chemoradiotherapy, when possible. Age is an important consideration in this disease, as older age is associated with shorter survival and a higher risk of treatment‐related toxicity.\ud \ud Objectives:\ud To determine the most effective and best‐tolerated approaches for the treatment of elderly people with newly diagnosed glioblastoma. To summarise current evidence for the incremental resource use, utilities, costs and cost‐effectiveness associated with these approaches.\ud \ud Search methods:\ud We searched electronic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase to 3 April 2019, and the NHS Economic Evaluation Database (EED) up to database closure. We handsearched clinical trial registries and selected neuro‐oncology society conference proceedings from the past five years.\ud \ud Selection criteria:\ud Randomised trials (RCTs) of treatments for glioblastoma in elderly people. We defined ‘elderly' as 70+ years but included studies defining ‘elderly' as over 65+ years if so reported.\ud \ud Data collection and analysis:\ud We used standard Cochrane methods for study selection and data extraction. Where sufficient data were available, treatment options were compared in a network meta‐analysis (NMA) using Stata software (version 15.1). For outcomes with insufficient data for NMA, pairwise meta‐analysis were conducted in RevMan. The GRADE approach was used to grade the evidence.\ud \ud Main results:\ud We included 12 RCTs involving approximately 1818 participants. Six were conducted exclusively among elderly people (either defined as 65 years or older or 70 years or older) with newly diagnosed glioblastoma, the other six reported data for an elderly subgroup among a broader age range of participants. Most participants were capable of self‐care. Study quality was commonly undermined by lack of outcome assessor blinding and attrition. NMA was only possible for overall survival; other analyses were pair‐wise meta‐analyses or narrative syntheses.\ud \ud Seven trials contributed to the NMA for overall survival, with interventions including supportive care only (one trial arm); hypofractionated radiotherapy (RT40; four trial arms); standard radiotherapy (RT60; five trial arms); temozolomide (TMZ; three trial arms); chemoradiotherapy (CRT; three trial arms); bevacizumab with chemoradiotherapy (BEV_CRT; one trial arm); and bevacizumab with radiotherapy (BEV_RT). Compared with supportive care only, NMA evidence suggested that all treatments apart from BEV_RT prolonged survival to some extent.\ud \ud Overall survival:\ud \ud High‐certainty evidence shows that CRT prolongs overall survival (OS) compared with RT40 (hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.56 to 0.80) and low‐certainty evidence suggests that CRT may prolong overall survival compared with TMZ (TMZ versus CRT: HR 1.42, 95% CI 1.01 to 1.98). Low‐certainty evidence also suggests that adding BEV to CRT may make little or no difference (BEV_CRT versus CRT: HR 0.83, 95% CrI 0.48 to 1.44). We could not compare the survival effects of CRT with different radiotherapy fractionation schedules (60 Gy/30 fractions and 40 Gy/15 fractions) due to a lack of data. When treatments were ranked according to their effects on OS, CRT ranked higher than TMZ, RT and supportive care only, with the latter ranked last. BEV plus RT was the only treatment for which there was no clear benefit in OS over supportive care only. \ud \ud One trial comparing tumour treating fields (TTF) plus adjuvant chemotherapy (TTF_AC) with adjuvant chemotherapy alone could not be included in the NMA as participants were randomised after receiving concomitant chemoradiotherapy, not before. Findings from the trial suggest that the intervention probably improves overall survival in this selected patient population.\ud \ud We were unable to perform NMA for other outcomes due to insufficient data. Pairwise analyses were conducted for the following.\ud \ud Quality of life:\ud \ud Moderate‐certainty narrative evidence suggests that overall, there may be little difference in QoL between TMZ and RT, except for discomfort from communication deficits, which are probably more common with RT (1 study, 306 participants, P = 0.002). Data on QoL for other comparisons were sparse, partly due to high dropout rates, and the certainty of the evidence tended to be low or very low.\ud \ud Progression‐free survival:\ud \ud High‐certainty evidence shows that CRT increases time to disease progression compared with RT40 (HR 0.50, 95% CI 0.41 to 0.61); moderate‐certainty evidence suggests that RT60 probably increases time to disease progression compared with supportive care only (HR 0.28, 95% CI 0.17 to 0.46), and that BEV_RT probably increases time to disease progression compared with RT40 alone (HR 0.46, 95% CI 0.27 to 0.78). Evidence for other treatment comparisons was of low‐ or very low‐certainty.\ud \ud Severe adverse events:\ud \ud Moderate‐certainty evidence suggests that TMZ probably increases the risk of grade 3+ thromboembolic events compared with RT60 (risk ratio (RR) 2.74, 95% CI 1.26 to 5.94; participants = 373; studies = 1) and also the risk of grade 3+ neutropenia, lymphopenia, and thrombocytopenia. Moderate‐certainty evidence also suggests that CRT probably increases the risk of grade 3+ neutropenia, leucopenia and thrombocytopenia compared with hypofractionated RT alone. Adding BEV to CRT probably increases the risk of thromboembolism (RR 16.63, 95% CI 1.00 to 275.42; moderate‐certainty evidence).\ud \ud Economic evidence:\ud \ud There is a paucity of economic evidence regarding the management of newly diagnosed glioblastoma in the elderly. Only one economic evaluation on two short course radiotherapy regimen (25 Gy versus 40 Gy) was identified and its findings were considered unreliable.\ud \ud Authors' conclusions:\ud For elderly people with glioblastoma who are self‐caring, evidence suggests that CRT prolongs survival compared with RT and may prolong overall survival compared with TMZ alone. For those undergoing RT or TMZ therapy, there is probably little difference in QoL overall. Systemic anti‐cancer treatments TMZ and BEV carry a higher risk of severe haematological and thromboembolic events and CRT is probably associated with a higher risk of these events. Current evidence provides little justification for using BEV in elderly patients outside a clinical trial setting. Whilst the novel TTF device appears promising, evidence on QoL and tolerability is needed in an elderly population. QoL and economic assessments of CRT versus TMZ and RT are needed. More high‐quality economic evaluations are needed, in which a broader scope of costs (both direct and indirect) and outcomes should be included.

In 2016 there were 5250 brain cancer deaths in the UK. Standard treatment is surgical resection followed by chemo-radiotherapy. In most cases of diffuse glioma, complete tumour resection is not feasible. Many chemotherapy drugs have untested penetration through the blood brain barrier, potentially leading to sub-therapeutic concentrations in the tumour. There is need to refine current treatment strategies in relation to the understanding of tumour biology, and rapidly introduce and evaluate novel therapeutic approaches and agents through delivering rigorous clinical trials. The TESSA JOWELL BRAIN MATRIX Study will evaluate the feasibility of delivering precision medicine for brain cancer patients within the NHS. A multicentre, platform feasibility study of 1200 patients with diffuse glioma will build on the 100,000 genome project to develop and evaluate an infrastructure to collect and integrate: 1) real time comprehensive integrated molecular analysis, including whole genome sequencing and epigenetic classification; 2) serial sampling and annotation of tumours; 3) collection of matched clinical data; 4) assessment of patient quality of life; 5) centralised radiological review and response assessment as per RANO criteria. Once developed this will allow rapid introduction of therapeutic trials to specific patient groups. Secondary objectives include: understanding the association between extent of resection and molecular stratification to refine the role of surgery; optimisation and harmonisation of protocols to best collect, manage and store tissue, clinical data, and radiological images in order to provide a resource for researchers, both within and outside of the study. Improve patient recruitment by identifying and removing recruitment barriers and improve the information and consent processes for patients. Promote the development of a national network with expertise in brain cancer. Enrolment of the first patient is expected in late 2019. For further information, please contact the Brain Matrix Trial Office BrainMatrix@trials.bham.ac.uk.

The National Cancer Research Institute (NCRI) is a partnership of charity and government research funders whose purpose is to improve health and quality of life by accelerating progress in cancer-related research through collaboration. Under this umbrella, the NCRI Brain Tumor Clinical Studies Group is focused on improving clinical outcomes for adult patients with brain and central nervous system tumors, including those with brain metastasis from other primary sites. This document discusses the current state of clinical brain tumor research in the United Kingdom and the challenges to increasing study and trial opportunities for patients. The clinical research priorities are defined along with a strategy to strengthen the existing brain tumor research network, improve access to tissue and imaging and to develop the future leadership for brain tumor research in the United Kingdom. This strategy document may serve as a framework for other organizations and countries.

Background The diagnosis and treatment of a brain or spinal cord tumour can have a huge impact on the lives of patients and their families with family caregiving often resulting in considerable burden and distress. Meeting the support needs of family caregivers is critical to maintain their emotional and physical health. Although support for caregivers is becoming more widely available, large‐scale implementation is hindered by a lack of high‐quality evidence for its effectiveness in the neuro‐oncology caregiver population. Objectives To assess the effectiveness of supportive interventions at improving the well‐being of caregivers of people with a brain or spinal cord tumour. To assess the effects of supportive interventions for caregivers in improving the physical and emotional well‐being of people with a brain or spinal cord tumour and to evaluate the health economic benefits of supportive interventions for caregivers. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 7), MEDLINE via Ovid, and Embase via Ovid. We also handsearched relevant published conference abstracts (previous five years), publications in the two main journals in the field (previous year), searched for ongoing trials via ClinicalTrials.gov, and contacted research groups in the field. The initial search was in March 2017 with an update in August 2018 (handsearches completed in January 2019). Selection criteria We included all randomised controlled trials (RCTs) where caregivers of neuro‐oncology patients constituted more than 20% of the sample and which evaluated changes in caregiver well‐being following any supportive intervention. Data collection and analysis Two review authors independently selected studies and carried out risk of bias assessments. We aimed to extract data on the outcomes of psychological distress, burden, mastery, quality of patient–caregiver relationship, quality of life, and physical functioning. Main results In total, the search identified 2102 records, of which we reviewed 144 in full text. We included eight studies. Four interventions focused on patient–caregiver dyads and four were aimed specifically at the caregiver. Heterogeneity of populations and methodologies precluded meta‐analysis. Risk of bias varied, and all studies included only small numbers of neuro‐oncology caregivers (13 to 56 participants). There was some evidence for positive effects of caregiver support on psychological distress, mastery, and quality of life (low to very low certainty of evidence). No studies reported significant effects on caregiver burden or quality of patient–caregiver relationship (low to very low certainty of evidence). None of the studies assessed caregiver physical functioning. For secondary outcomes (patient emotional or physical well‐being; health economic effects), we found very little to no evidence for the effectiveness of caregiver support. We identified five ongoing trials. Authors' conclusions The eight small‐scale studies included employed different methodologies across different populations, with low certainty of evidence overall. It is not currently possible to draw reliable conclusions regarding the effectiveness of supportive interventions aimed at improving neuro‐oncology caregiver well‐being. More high‐quality research is needed on support for family caregivers of people diagnosed, and living, with a brain or spinal cord tumour.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:\ud \ud To determine the most effective and best‐tolerated approaches for the treatment of elderly people with newly diagnosed glioblastoma.\ud \ud To summarise current evidence for the incremental resource use, utilities, costs and cost‐effectiveness associated with the different management strategies for newly diagnosed glioblastoma among adults aged over 70 years.

This chapter, ‘Patient and caregiver advocacy’, examines the context for advocacy for people who are living with a brain tumour, why it is different, how it manifests itself, and what advocacy looks like. It explores the challenges that come with living with a brain tumour and how advocacy can alleviate these challenges. The different advocacy roles are reviewed, including an exploration of how some patients can become advocates for others, while others do not. Underpinning this however is a need to be responsive and agile throughout what can be a very fluid, dynamic, and complex journey. Anyone who finds themselves supporting someone who is living with a brain tumour will find this chapter useful.

The diagnosis of a brain tumour is one of the most shocking pieces of news that people can receive. Brain tumours know no geographic boundaries. They strike people of all ages with equal ferocity—from tiny babies to the elderly. They intersect three major disease areas

Daily interactions with patients and caregivers who are living with a brain tumour reveal that self-management practices, whilst being provided routinely in some places, tend to be on an ad hoc basis, reactive and unplanned. Patients do not know what support is available to them, where to seek help or what questions they should be asking. A shift to being empowered begins at the point of diagnosis, with a collaborative and interactive relationship between patients and healthcare professionals, which empowers patients to take on responsibility for their condition with the appropriate clinical support. This chapter explores why shared engagement is a prerequisite for optimised clinical care, what this looks like and how to achieve it so that it becomes the cornerstone of every communication between people living with a brain tumour and their clinical team.

BACKGROUND Fatigue is common and disabling for brain tumour patients. We studied the feasibility of two innovative lifestyle coaching interventions for high fatigue. METHODS Multi-centre phase II feasibility RCT (ISRCTN17883425). Adult primary brain tumour outpatients reporting significant fatigue (Brief Fatigue Inventory [BFI] score 4+), were randomised to one of three arms: Control; Health Coaching (“HC”, comprising eight structured coaching sessions on lifestyle behaviours); or HC plus Activation Coaching (“HC+AC”, adding two structured interviews targeting motivation to change). Outcomes were measured at baseline (T0), after interventions (T1), and at 16 weeks (T2). The primary outcome of feasibility was required for both recruitment (aim: average n= 5 fatigued patients recruited/month) and retention (aim: minimum 60% retention at T2). Secondary pilot outcomes included change in fatigue, depressive symptom, and QOL measures. RESULTS Over a nine-month recruitment period, n= 46 fatigued brain tumour patients were recruited (average n=5.1/month) and n= 34 were retained to endpoint (retention at T2= 73%), meeting the primary outcome of feasibility. Surprisingly, fatigue reduced significantly after HC (T1 mean change in BFI score from T0 baseline, relative to the equivalent change in control group: HC= -2.3 points [95%CI -3.4/-0.3]; HC+AC= -2.0 [-2.9/+0.1]; ANOVA p= 0.02) and was reduced in magnitude in both intervention groups at T2 (p= N.S). Both interventions also improved depressive symptoms (T1 mean change in HADS-Depression: HC= -2.0 points [-5.6/-0.1]; HC+AC= -2.9 [-6.5/-1.0]; Kruskal-Wallis p= 0.02). Patient-nominated QOL outcomes improved persistently after HC+AC (T2 mean change in PSYCHLOPS score: HC= -2.4 points [-5.4/+2.8]; HC+AC= -6.1 [-9.2/-0.8]; ANOVA p= 0.01). CONCLUSION Innovative coaching interventions, focused on lifestyle factors, are feasible to deliver to fatigued brain tumour patients. Preliminary signals suggest that these non-drug approaches may benefit several mediators of quality of life and warrant further study.

BACKGROUND BT-LIFE is a multi-centre RCT of novel lifestyle coaching treatments for fatigued brain tumour patients. To our knowledge it is also the first example of ‘multi-sectoral research’ to combine healthcare, private, and charity sectors in this population. To maximise learning, the trial team devised a structured reflection opportunity to ask, “What went well and what would we do differently next time?” METHOD After trial closedown we convened a six-hour ‘focus group’ for management, principle investigators, research assistants, interventionists, qualitative researchers, trial statisticians, and the funder. Discussion was structured using a ‘timeline’ wall-chart which attendees freely populated with post-it notes summarising learning points from the trial. Minutes were taken in duplicate. RESULTS In total n=19 team members contributed. Many points were study-specific and will be used internally to plan a larger trial. Among points of wider interest, examples of success included: using regular teleconferences to co-ordinate a cohesive and highly collaborative team; obtaining secure nhs.net email addresses to facilitate multi-sectoral communication; and the clear value of employing one part-time research assistant per centre instead of relying on busy clinical staff to recruit. General future learning points included: speak to the prospective sponsor and ethical committees when writing the grant application to avoid pitfalls and facilitate faster opening if funding is secured; consider preceding emails with a phone call to ‘lay the ground’ in time-sensitive situations; identify staff training requirements as early as possible and cascade aggressively; and be sensitive to the fact that inter-sectoral attitudes and practices may vary widely and need actively monitored and managed. Therefore frequent and secure communication, pro-active problem-spotting, and inter-sectoral value alignment appear critical for success. CONCLUSION BT-LIFE provides many useful lessons for anyone interested in running multi-sectoral research.

INTRODUCTION: There is no consensus regarding the utility of prophylactic anti-Epileptic Drugs (AED) given to patients with supratentorial glioma before surgery, who have not had seizures. Newer AEDs have fewer adverse effects but their efficacy in preventing new onset seizures remains to be proven. In 2016, we surveyed all members of the Society of British Neurosurgeons (SBNS) to determine current practice and establish whether a randomised controlled trial (RCT) of AED vs no AED would be feasible. METHODS: Survey of neurosurgeons/centres dealing with glioma patients in the UK regarding:(i) routine use of AED in patients with glioma(ii) preferred AED (iii) willingness to participate in a RCT of prophylactic AED(iv) were patients seen in a dedicated specialist neurosurgical clinic before surgery. A four point scale was used regarding usage of AEDs “almost always”, “usually”, “rarely”, “almost never” to avoid centering bias. RESULTS: 71% of 35 respondents almost never prescribed AEDs while 14% almost always prescribed AEDs. 51.4% would use Levetiracetam, 11.4% phenytoin and 37.1% not applicable. 74.3% would be interested in participating in a RCT. 60% of patients were seen in a dedicated specialist neurosurgical clinic before surgery. Conclusions: Based on responses of the survey a UK RCT trial of Levetiracetam vs no AED was considered feasible and a proposal (Seizure Prophylaxis IN Glioma - SPRING) was submitted to NIHR HTA. The application was successful. SPRING will start recruiting patients over three years from Jan 2019 in 15 neurosurgical centres across the UK. ACKNOWLEDGEMENTS: National Institute of Health Research for funding, (NIHR), and UCB for supplying AED.

BACKGROUND: brainstrust recognised a need to develop the conversation about cancer data beyond traditional indicators. METHODS: Since 2015, brainstrust has worked with the National Cancer Registration and Analysis Service (NCRAS) to: Explore data in new ways to address important questions for the brain tumour community. Establish a process that can be used by other cancer sites. NCRAS produced Pilot Standard Output Tables for brain tumours covering incidence, diagnosis routes, treatment and survival. brainstrust explored the findings of this first data release and identified four themes on which to report, the first being Non Malignant Brain Tumours (NMBTs). RESULTS: 1. NMBTs are a diverse group of tumours, including meningiomas, schwannomas, pituitary adenomas and other tumours. 2. About 9,000 primary brain tumours are diagnosed every year. 50% are non-malignant. 3. Over 1 in 10 people with a NMBT will not survive the first year (over 500 deaths annually). 4. When crude[1] and net[2] survival data is considered, there is no difference in the > 49 age cohorts and the difference is smaller than 0.6% in the > 69 age cohorts. 5. 30% of people with a NMBT are diagnosed through A and E. CONCLUSION: Key recommendations: 1. A need for public understanding, resources and information. 2. Support for people with a NMBT should be stratified more effectively according to a clear set of determinants. 3. Relevant and timely models of support should be developed, including high quality information and involvement of palliative support. 4. There must be parity of voice between non-malignant and malignant brain tumour community. [1] Probability of death in the real world where you may die of other causes before the cancer kills you. [2] Probability of death in a hypothetical world where the cancer under study is the only possible cause of death

BACKGROUND Glioma patients may experience behavioral and personality changes (BPC), which have a negative impact on the lives of both brain tumor patients and their relatives. The extent of BPC is currently unknown, and it is unclear if available assessment tools cover all aspects of BPC that are relevant for glioma patients. This study aimed to determine which characteristics of BPC are relevant for glioma patients. METHODS Possible characteristics of BPC were identified in the literature and based on expert opinion. Next, these 49 items were presented to patients and caregivers/former caregivers in an online survey launched via the International Brain Tumour Alliance. Participants were requested to indicate the relevance for each characteristic on a 4-point Likert scale ranging from ‘not at all’ to ‘very much’. In addition, they had to indicate which three characteristics had most impact on their daily life, and if characteristics were missing. RESULTS Completed surveys were obtained from 141 respondents, of which 36% were patients, 50% caregivers and 14% unknown. Most patients had grade II or IV glioma (29% vs 38%). Of 49 characteristics, 35 were reported as relevant in at least 25% (range all characteristics: 7–44%). Patients (n=50) and caregivers (n=70) rated different characteristics as most important. Common characteristics were lack of motivation, change in being socially active, not able to finish things and change in level of irritation. There were no characteristics reported to be missing by ≥5 respondents. CONCLUSION The majority of characteristics were rated as relevant in >25% of respondents, and patients and caregivers differed in which were most relevant. A clear definition based on these results is therefore difficult to establish. A next step would be to perform a cluster analysis of patients and caregivers separately, and discuss the results with experts, to reach consensus on an appropriate definition.

BACKGROUND: Extent of resection is considered to be a prognostic factor in neuro‐oncology. Intraoperative imaging technologies are designed to help achieve this goal. It is not clear whether any of these sometimes very expensive tools (or their combination) should be recommended as standard care for people with brain tumours. We set out to determine if intraoperative imaging technology offers any advantage in terms of extent of resection over standard surgery and if any one technology was more effective than another. OBJECTIVES: To establish the overall effectiveness and safety of intraoperative imaging technology in resection of glioma. To supplement this review of effects, we also wished to identify cost analyses and economic evaluations as part of a Brief Economic Commentary (BEC). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 7, 2017), MEDLINE (1946 to June, week 4, 2017), and Embase (1980 to 2017, week 27). We searched the reference lists of all identified studies. We handsearched two journals, the Journal of Neuro‐Oncology and Neuro‐oncology, from 1991 to 2017, including all conference abstracts. We contacted neuro‐oncologists, trial authors, and manufacturers regarding ongoing and unpublished trials. SELECTION CRITERIA: Randomised controlled trials evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included intraoperative MRI (iMRI), fluorescence‐guided surgery, ultrasound, and neuronavigation (with or without additional image processing, e.g. tractography). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma. MAIN RESULTS: We identified four randomised controlled trials, using different intraoperative imaging technologies: iMRI (2 trials including 58 and 14 participants, respectively); fluorescence‐guided surgery with 5‐aminolevulinic acid (5‐ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around autumn 2018. We identified no trials for ultrasound. Meta‐analysis was not appropriate due to differences in the tumours included (eloquent versus non‐eloquent locations) and variations in the image guidance tools used in the control arms (usually selective utilisation of neuronavigation). There were significant concerns regarding risk of bias in all the included studies. All studies included people with high‐grade glioma only. Extent of resection was increased in one trial of iMRI (risk ratio (RR) of incomplete resection 0.13, 95% confidence interval (CI) 0.02 to 0.96; 1 study, 49 participants; very low‐quality evidence) and in the trial of 5‐ALA (RR of incomplete resection 0.55, 95% CI 0.42 to 0.71; 1 study, 270 participants; low‐quality evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants, therefore the trial provides very low‐quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection. Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low‐quality evidence). Overall, reported events were low in most trials. There was no clear evidence of improvement in overall survival with 5‐ALA (hazard ratio 0.83, 95% CI 0.62 to 1.07; 1 study, 270 participants; low‐quality evidence). Progression‐free survival data were not available in an appropriate format for analysis. Data for quality of life were only available for one study and suffered from significant attrition bias (very low‐quality evidence). AUTHORS' CONCLUSIONS: Intra‐operative imaging technologies, specifically iMRI and 5‐ALA, may be of benefit in maximising extent of resection in participants with high grade glioma. However, this is based on low to very low quality evidence, and is therefore very uncertain. The short‐ and long‐term neurological effects are uncertain. Effects of image‐guided surgery on overall survival, progression‐free survival, and quality of life are unclear. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, a non‐systematic review of economic studies suggested that compared with standard surgery use of image‐guided surgery has an uncertain effect on costs and that 5‐aminolevulinic acid was more costly. Further research, including studies of ultrasound‐guided surgery, is needed.

Glioblastoma is the commonest malignant brain tumor in adults. Most patients develop progressive disease before they die. However, survival after developing progressive disease is infrequently reported. We identified patients with histologically proven disease who were treated with concurrent chemoradiotherapy during 2006–2013. We analyzed overall survival (OS), progression-free survival and postprogression survival (PPS) in relation to age, O6-methylguanine-DNA methyltransferase promoter methylation and extent of surgical resection. We identified 166 patients. Median survival was 13.5 months; 2-year OS was 21.7%. Median progression-free survival and PPS were 7.03 and 4.53 months, respectively. Age and extent of surgical resection were correlated with OS. Only the extent of surgical resection was associated with PPS. Our work suggests that the established prognostic factors for glioblastoma do not appear to help predict PPS.

Background Despite increasing international interest, there is a lack of evidence about the most efficient, effective and acceptable ways to implement patient and public involvement (PPI) in clinical trials. Objective To identify the priorities of UK PPI stakeholders for methodological research to help resolve uncertainties about PPI in clinical trials. Design A modified Delphi process including a two round online survey and a stakeholder consensus meeting. Participants In total, 237 people registered of whom 219 (92%) completed the first round. One hundred and eighty‐seven of 219 (85%) completed the second; 25 stakeholders attended the consensus meeting. Results Round 1 of the survey comprised 36 topics; 42 topics were considered in round 2 and at the consensus meeting. Approximately 96% of meeting participants rated the top three topics as equally important. These were as follows: developing strong and productive working relationships between researchers and PPI contributors; exploring PPI practices in selecting trial outcomes of importance to patients; and a systematic review of PPI activity to improve the accessibility and usefulness of trial information (eg participant information sheets) for participants. Conclusions The prioritized methodological research topics indicate important areas of uncertainty about PPI in trials. Addressing these uncertainties will be critical to enhancing PPI. Our findings should be used in the planning and funding of PPI in clinical trials to help focus research efforts and minimize waste.

International audience; Patients with glioma present with complex palliative care needs throughout their disease trajectory. The life-limiting nature of gliomas and the presence of specific symptoms related to neurological deterioration necessitate an appropriate and early palliative care approach. The multidisciplinary palliative care task force of the European Association of Neuro-Oncology did a systematic review of the available scientific literature to formulate the best possible evidence-based recommendations for the palliative care of adult patients with glioma, with the aim to reduce symptom burden and improve the quality of life of patients and their caregivers, particularly in the end-of-life phase. When recommendations could not be made because of the scarcity of evidence, the task force either used evidence from studies of patients with systemic cancer or formulated expert opinion. Areas of palliative care that currently lack evidence and thus deserve attention for further research are fatigue, disorders of behaviour and mood, interventions for the needs of caregivers, and timing of advance care planning.

Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016.To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue.For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials.We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings.Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes.The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT.There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.

Neurocognitive deficits are common with brain tumors. If assessed at presentation using detailed neurocognitive tests, problems are detected in 80 % of cases. Neurocognition may be affected by the tumor, its treatment, associated medication, mood, fatigue, and insomnia. Interpretation of neurocognitive problems should be considered in the context of these factors. Early post-operative neurocognitive rehabilitation for brain tumor patients will produce rehabilitation outcomes (e.g., quality of life, improved physical function, subjective neurocognition) equivalent to stroke, multiple sclerosis, and head injury, but the effect size and duration of benefit needs further research. In stable patients treated with radiotherapy +/- chemotherapy, the most frequent causes of distress include neurocognitive problems, psychological factors of anxiety, depression, fatigue, and sleep. Exercise, neurocognitive training, neurocognitive behavioral therapy, and medications to treat fatigue, behavior, memory, mood, and removal of drugs that may be associated with neurocognitive side effects (e.g., anti-epileptic drugs) all show promise in helping patients to manage the effects of their neurocognitive impairments better. As these are complex symptoms, multidisciplinary expertise is necessary to evaluate the influence of each variable to plan appropriate support and intervention. Neurocognitive rehabilitation should therefore occur in parallel with disease-centered, medical management from the outset. It should not occur in series, as a restricted phase in a patient's pathway. It should be considered in the pre- and post-operative period where there are good prospects of recovery, as one would for any brain-injured patient, so that the person may reach their optimal physical, sensory, intellectual, psychological, and social functional level. Yet the identification and selection of patients for early neurological rehabilitation and routine evaluation of cognition is uncommon in neurosurgical wards.

BACKGROUND Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39-58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. METHODS/DESIGN A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. TRIAL REGISTRATION ISRCTN71502099 on 19 May 2014.