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William Sage,1 Rocío Fernández-Méndez,1 Anna Crofton,2 Michael J Gifford,3 Alexey Bannykh,3 Constantinos Chrysaphinis,4 Emma Tingley,4 Helen Bulbeck,5 Mita Brahmbhatt,1 John D Pickard,1 Fiona M Walter,6 Andrew Brodbelt,2 Stephen J Price,1 Alexis J Joannides1 1Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 2Department of Neurosurgery, The Walton Centre, Liverpool, UK; 3Mountain Hare Consulting, London, UK; 4The Brain Tumour Charity, Farnborough, UK; 5Brainstrust, Cowes, Isle of Wight, UK; 6Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK 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. Keywords: patient experience, brain cancer, brain tumors, neuro-oncology pathway

Purpose: Image-based data mining (IBDM) is a voxel-based analysis technique to investigate dose-response. Most often, IBDM uses radiotherapy planning CTs because of their broad accessibility, however, it was unknown whether CT provided sufficient soft tissue contrast for brain IBDM. This study evaluates whether MR-based IBDM improves upon CT-based IBDM for studies of children with brain tumours., Methods: We compared IBDM pipelines using either CT- or MRI-based spatial normalisation in 128 children (ages 3.3-19.7 years) who received photon radiotherapy for primary brain tumours at a single institution. We quantified spatial-normalisation accuracy using contour comparison measures (centre-of-mass separation, average contour distance-to-agreement (DT avg ), and Hausdorff distance) at multiple anatomic loci. We performed an end-to-end test of CT- and MRI-IBDM using modified clinical dose distributions and simulated effect labels to detect associations in pre-defined anatomic loci. Accuracy was assessed via sensitivity and specificity., Results: Spatial normalisation accuracy was comparable for both modalities, with a significant but small improvement for MRI compared to CT in all structures except the brainstem. The median (range) difference between the DT avg for the two pipelines was 0.37 (0.00-2.91) mm. The end-to-end test revealed no significant difference in sensitivity of the IBDM-identified regions for the two pipelines. Specificity slightly improved for MR-IBDM at the 99% significance level., Conclusion: CT-based IBDM was comparable to MR-based IBDM, despite a small advantage in spatial normalisation accuracy with MRI. The use of CT-IBDM over MR-IBDM is useful for multi-institutional retrospective IBDM studies, where the availability of standardised MRI data can be limited., 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 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Glioblastoma is the deadliest primary malignant brain tumor in adults with limited treatment options and an average survival time of 12-18 months in the United Kingdom. In addition, glioblastoma has a highly detrimental impact on physical, cognitive, and emotional well-being, leaving substantial unmet needs for patients and caregivers. This study aimed to identify unmet needs in people with newly diagnosed glioblastoma and opportunities to mitigate them., Methods: Utilizing Delphi methodology, an initial roundtable discussion with patient advocacy experts from 5 brain tumor organizations in the United Kingdom informed the development of 2 rounds of surveys across 9 domains (diagnosis, treatment, integrated care, support beyond treatment, quality of life, access to new treatments, access to trials, measures to ease the burden, and impact of COVID-19). Consensus was predefined as ≥70% agreement., Results: A total of 17 Delphi panelists (glioblastoma patients, caregivers, and patient representatives) completed the first round of questionnaires and 26 completed the second. Consensus was reached on 16/21 questions (76.2%) and 7/9 domains. Panelists reached a consensus on key questions including the high frequency of diagnosis via emergency departments, the lack of effective personalized treatments and holistic care, the high caregiver burden, the lack of awareness and availability of access to clinical trials, and the negative impact of COVID-19 on glioblastoma care., Conclusions: Significant unmet needs exist for newly diagnosed glioblastoma patients in the United Kingdom, highlighting the demand for increased research funding, comprehensive patient care, caregiver support, enhanced awareness and access to clinical trials, and new treatments., Competing Interests: H.B.: Participated as a patient advocate on a panel in the European Society for Medical Oncology (ESMO) Congress 2023. No organizational conflicts of interest to declare. K.N.: No personal conflicts of interest to declare. Regarding her organization, in October 2023, it was confirmed that Novocure will be the headline sponsor of the Brain Tumour Research Wear a Hat Day fundraising event in 2024 including financial support. At the time of the project initiation and patient surveys, Brain Tumour Research had nothing to declare. K.O.: No personal conflicts of interest to declare. For transparency, her organization’s funding sources for 2022 and 2023 are as follows: The IBTA received grant and sponsorship funding from the following companies and organizations: Bayer, Bristol Myers Squibb, Elekta, GW Pharma/Jazz Pharmaceuticals, Medac, Novartis, Novocure, Northwest Biotherapeutics, Pfizer, Photonamic, the Sontag Foundation, STOPhersentumoren, Daiichi Sankyo, GT Medical Technologies, Menarini Stemline, Regeneron, Roche, Seagen, and Servier. Additionally, the IBTA received honoraria for speaking and other roles (ie, advisory board membership) and/or reimbursement of expenses (ie, travel and accommodation) from the European Cancer Organisation, European Society for Medical Oncology Congress 2023, Sanofi, Novocure, Seagen, Bristol Myers Squibb, Novartis, and Eisai. T.M.S.: No conflicts of interest to declare at both personal and organizational levels., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Purpose: Patients with glioblastoma who are older or have poor performance status (PS) experience particularly poor clinical outcomes. At the time of study initiation, these patients were treated with short-course radiation therapy (40 Gy in 15 fractions). Olaparib is an oral inhibitor of the DNA repair enzyme poly (ADP-ribose) polymerase (PARP) that is well tolerated as a single agent but exacerbates acute radiation toxicity in extracranial sites. Preclinical data predicted that PARP inhibitors would enhance radiosensitivity in glioblastoma without exacerbating adverse effects on the normal brain., Methods and Materials: Phase 1 of the PARADIGM trial was a 3+3 dose-escalation study testing olaparib in combination with radiation therapy (40 Gy 15 fractions) in patients with newly diagnosed glioblastoma who were unsuitable for radical treatment either because they were aged 70 years or older (World Health Organization PS 0-1) or aged 18 to 69 years with PS 2. The primary outcome was the recommended phase 2 dose of olaparib. Secondary endpoints included safety and tolerability, overall survival, and progression-free survival. Effects on cognitive function were assessed via the Mini Mental State Examination., Results: Of 16 eligible patients (56.25% male; median age, 71.5 years [range, 44-78]; 75% PS 0-1), 1 dose-limiting toxicity was reported (grade 3 agitation). Maximum tolerated dose was not reached and the recommended phase 2 dose was determined as 200 mg twice daily. Median overall survival and progression-free survival were 10.8 months (80% CI, 7.3-11.4) and 5.5 months (80% CI, 3.9-5.9), respectively. Mini Mental State Examination plots indicated that cognitive function was not adversely affected by the olaparib-radiation therapy combination., Conclusions: Olaparib can be safely combined with hypofractionated brain radiation therapy and is well tolerated in patients unsuitable for radical chemoradiation. These results enabled initiation of a randomized phase 2 study and support future trials of PARP inhibitors in combination with radiation therapy for patients with brain tumors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

Introduction: Glioblastoma (GBM) is the most common adult primary malignant brain tumour. The condition is incurable and, despite aggressive treatment at first presentation, almost all tumours recur after a median of 7 months. The aim of treatment at recurrence is to prolong survival and maintain health-related quality of life (HRQoL). Chemotherapy is typically employed for recurrent GBM, often using nitrosourea-based regimens. However, efficacy is limited, with reported median survivals between 5 and 9 months from recurrence. Although less commonly used in the UK, there is growing evidence that re-irradiation may produce survival outcomes at least similar to nitrosourea-based chemotherapy. However, there remains uncertainty as to the optimum approach and there is a paucity of available data, especially with regards to HRQoL. Brain Re-Irradiation Or Chemotherapy (BRIOChe) aims to assess re-irradiation, as an acceptable treatment option for recurrent IDH-wild-type GBM., Methods and Analysis: BRIOChe is a phase II, multi-centre, open-label, randomised trial in patients with recurrent GBM. The trial uses Sargent's three-outcome design and will recruit approximately 55 participants from 10 to 15 UK radiotherapy sites, allocated (2:1) to receive re-irradiation (35 Gy in 10 daily fractions) or nitrosourea-based chemotherapy (up to six, 6-weekly cycles). The primary endpoint is overall survival rate for re-irradiation patients at 9 months. There will be no formal statistical comparison between treatment arms for the decision-making primary analysis. The chemotherapy arm will be used for calibration purposes, to collect concurrent data to aid interpretation of results. Secondary outcomes include HRQoL, dexamethasone requirement, anti-epileptic drug requirement, radiological response, treatment compliance, acute and late toxicities, progression-free survival., Ethics and Dissemination: BRIOChe obtained ethical approval from Office for Research Ethics Committees Northern Ireland (reference no. 20/NI/0070). Final trial results will be published in peer-reviewed journals and adhere to the ICMJE guidelines., Trial Registration Number: ISRCTN60524., Competing Interests: Competing interests: FS reports grants from Cancer Research UK, during the conduct of the study. DS-M reports grants from Jon Moulton Charitable Foundation, grants from Yorkshire Cancer Research, during the conduct of the study. LM reports grants from Jon Moulton Charity Trust, grants from Cancer Research UK, during the conduct of the study; grants from Yorkshire Cancer Research, outside the submitted work. SRB reports grants from Jon Moulton Charitable Foundation, grants from Yorkshire Cancer Research, during the conduct of the study. SS reports advisory board activity for Bayer, CeCaVa Laboratory Research project support, Apollomics., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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.)

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.)

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.

•There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).•TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.•Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.•There is a strong translational component within TORPEdO. Imaging and physics data along with blood, tissue collection will inform future studies in refining patient selection for IMPT., Competing Interests: 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., (© 2022 The Authors.)

Introduction: Surgery remains the mainstay for treatment of primary glioblastoma, followed by radiotherapy and chemotherapy. Current standard of care during surgery involves the intraoperative use of image-guidance and 5-aminolevulinic acid (5-ALA). There are multiple other surgical adjuncts available to the neuro-oncology surgeon. However, access to, and usage of these varies widely in UK practice, with limited evidence of their use. The aim of this trial is to investigate whether the addition of diffusion tensor imaging (DTI) and intraoperative ultrasound (iUS) to the standard of care surgery (intraoperative neuronavigation and 5-ALA) impacts on deterioration free survival (DFS)., Methods and Analysis: This is a two-stage, randomised control trial (RCT) consisting of an initial non-randomised cohort study based on the principles of the IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) stage-IIb format, followed by a statistically powered randomised trial comparing the addition of DTI and iUS to the standard of care surgery. A total of 357 patients will be recruited for the RCT. The primary outcome is DFS, defined as the time to either 10-point deterioration in health-related quality of life scores from baseline, without subsequent reversal, progressive disease or death., Ethics and Dissemination: The trial was registered in the Integrated Research Application System (Ref: 264482) and approved by a UK research and ethics committee (Ref: 20/LO/0840). Results will be published in a peer-reviewed journal. Further dissemination to participants, patient groups and the wider medical community will use a range of approaches to maximise impact., Trial Registration Number: ISRCTN38834571., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: There are no effective treatments for brain tumor-related fatigue. We studied the feasibility of two novel lifestyle coaching interventions in fatigued brain tumor patients., Methods: This phase I/feasibility multi-center RCT recruited patients with a clinically stable primary brain tumor and significant fatigue (mean Brief Fatigue Inventory [BFI] score ≥ 4/10). Participants were randomized in a 1-1-1 allocation ratio to: Control (usual care); Health Coaching ("HC", an eight-week program targeting lifestyle behaviors); or HC plus Activation Coaching ("HC + AC", further targeting self-efficacy). The primary outcome was feasibility of recruitment and retention. Secondary outcomes were intervention acceptability, which was evaluated via qualitative interview, and safety. Exploratory quantitative outcomes were measured at baseline (T0), post-interventions (T1, 10 weeks), and endpoint (T2, 16 weeks)., Results: n = 46 fatigued brain tumor patients (T0 BFI mean = 6.8/10) were recruited and 34 were retained to endpoint, establishing feasibility. Engagement with interventions was sustained over time. Qualitative interviews ( n = 21) suggested that coaching interventions were broadly acceptable, although mediated by participant outlook and prior lifestyle. Coaching led to significant improvements in fatigue (improvement in BFI versus control at T1: HC=2.2 points [95% CI 0.6, 3.8], HC + AC = 1.8 [0.1, 3.4], Cohen's d [HC] = 1.9; improvement in FACIT-Fatigue: HC = 4.8 points [-3.7, 13.3]; HC + AC = 12 [3.5, 20.5], d [HC and AC] = 0.9). Coaching also improved depressive and mental health outcomes. Modeling suggested a potential limiting effect of higher baseline depressive symptoms., Conclusions: Lifestyle coaching interventions are feasible to deliver to fatigued brain tumor patients. They were manageable, acceptable, and safe, with preliminary evidence of benefit on fatigue and mental health outcomes. Larger trials of efficacy are justified., Competing Interests: GA is a private personal trainer. Out-with the study he created the specific HC model utilized here and uses it in private practice. Within the study he was contracted to give HC to participants at the Edinburgh and Glasgow sites. HB and CC are employees of the UK brain tumor charity brainstrust which offers life coaching to brain tumor patients and their careers out-with the study. Within the study brainstrust was contracted to give AC to participants on all three sites. None of these individuals had any role in the collection, analysis, or interpretation of any data presented in this manuscript. All other authors report no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

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., Competing Interests: Competing interests: Due to their involvement in the study design, the study team members will not participate in the Delphi process or consensus meeting, other than in a facilitative role. Study team members will encourage engagement and participation in the Delphi process and consensus meeting by individuals within the networks of which they are part, as appropriate. AR is partially funded by NIHR Applied Research Collaborative West Midlands. SS is supported by Marie Curie core grant funding to the Marie Curie Palliative Care Research Centre, Cardiff University, grant reference MCC-FCO-11-C. MC is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for Patient Reported Outcomes Research and is a National Institute for Health Research (NIHR) Senior Investigator. She receives funding from the NIHR Birmingham Biomedical Research Centre, the NIHR Surgical Reconstruction and Microbiology Research Centre and NIHR ARC West Midlands at the at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Health Data Research UK, Innovate UK (part of UK Research and Innovation), Macmillan Cancer Support, UCB and GSK Pharma. MC has received personal fees from Astellas, Takeda, Merck, Daiichi Sankyo, Glaukos, GSK, Aparito Ltd, CIS Oncology and the Patient-Centered Outcomes Research Institute (PCORI) outside the submitted work. MC has led the development of SPIRIT-PRO and CONSORT-PRO international guidance and is a member of the SISAQOL and PROTEUS Consortia. OLA receives funding from the NIHR Birmingham Biomedical Research Centre (BRC), NIHR Applied Research Centre (ARC), West Midlands at the University of Birmingham and University Hospitals Birmingham NHS Foundation, Innovate UK (part of UK Research and Innovation), Gilead Sciences Ltd and Janssen Pharmaceuticals, Inc. OLA declares personal fees from Gilead Sciences Ltd, GlaxoSmithKline (GSK) and Merck outside the submitted work. LD has received research funding (as PI or collaborator) from the Brain Tumour Charity, EORTC Quality of Life Group, Innovative Medicines Initiatives, Dutch Cancer Society, ZonMw, National Institute for Health Research UK and crowd funding initiatives, although not related to this specific research. LD is involved in the EORTC (as chair of the Brain Tumour Group Quality of Life Committee) and in the development of EORTC questionnaires for brain tumour patients (IADL, BN20). LD is a representative of the RANO-PRO initiative. LD is associate Editor for Neuro Oncology, dealing with papers on clinical outcomes in brain tumours., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To 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., Design: Cross sectional survey., Setting: UK., Data Sources: NICE guidelines and supporting evidence., Eligibility Criteria: All 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., Results: Within 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 (<1%) considered the opportunity costs of implementation. No intervention considered the burden placed on individuals by these recommendations., Conclusion: Few 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., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: 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., Objectives: To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue., Search Methods: 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., Selection Criteria: 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., Data Collection and Analysis: 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., Main Results: 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., Authors' Conclusions: 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., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: Gliomas 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 Analysis: The 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 Dissemination: The 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 Number: NCT04274283, 18-Feb-2020; ISRCTN14218060, 03-Feb-2020., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Introduction: Meningioma 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 Analysis: Two 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 Dissemination: Institutional 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 Number: COMET study ID 1508., Competing Interests: Competing interests: MDJ received a grant from the National Institute for Health Research Health Technology Assessment programme for the Radiation versus Observation for Atypical Meningioma (ROAM) trial (NIHR ID: 12/173/14). MDJ received a grant from the National Institute for Health Research Health Technology Assessment programme 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). 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, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dohme, Tocagen, Adastra. The following for-profit companies have supported clinical trials and contracted research conducted by MP with payments made to his institution: Boehringer Ingelheim, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck Sharp & Dohme, Novocure, GlaxoSmithKline, AbbVie. MW has received research grants from Apogenix, Merck Sharp & Dohme, Merck (EMD) and Quercis, and honoraria for lectures or advisory board participation or consulting from Adastra, Bristol Myers Squibb, Medac, Merck Sharp & Dohme, Merck (EMD), Nerviano Medical Sciences, Novartis, Orbus, Philogen and yMabs., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Primary malignant brain tumours can have an unpredictable course, but high-grade gliomas typically have a relentlessly progressive disease trajectory. They can cause profound symptom burden, affecting physical, neurocognitive, and social functioning from an early stage in the illness. This can significantly impact on role function and on the experiences and needs of informal caregivers. Access to specialist palliative and supportive care early in the disease trajectory, for those with high-grade tumours in particular, has the potential to improve patients' and caregivers' quality of life. However, provision of palliative and supportive care for people with primary brain tumours - and their informal caregivers - is historically ill-defined and ad hoc, and the benefits of early palliative interventions have not been confirmed. It is therefore important to define the role and effectiveness of early referral to specialist palliative care services and/or the effectiveness of other interventions focused on palliating disease impact on people and their informal caregivers. This would help guide improvement to service provision, by defining those interventions which are effective across a range of domains, and developing an evidence-based model of integrated supportive and palliative care for this population., Objectives: To assess the evidence base for early palliative care interventions, including referral to specialist palliative care services compared to usual care, for improving outcomes in adults diagnosed with a primary brain tumour and their carers., Search Methods: We conducted searches of electronic databases, CENTRAL, MEDLINE, CINAHL, Web of Science, and PsycINFO (last searched 16 November 2021). We conducted searches to incorporate both qualitative and quantitative search terms. In addition to this, we searched for any currently recruiting trials in ClinicalTrials.gov and in the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal, and undertook citation tracking via Scopus. We also handsearched reference lists of potentially eligible systematic review articles to identify any other relevant studies, contacted experts in the field and searched key authors via Web of Science and searched SIGLE (System of Information on Grey Literature in Europe)., Selection Criteria: We included studies looking at early referral to specialist palliative care services - or early targeted palliative interventions by other healthcare professionals - for improving quality of life, symptom control, psychological outcomes, or overall survival as a primary or secondary outcome measure. Studies included randomised controlled trials (RCTs), non-randomised studies (NRS), as well as qualitative and mixed-methods studies where both qualitative and quantitative data were included. Participants were adults with a confirmed radiological and/or histological diagnosis of a primary malignant brain tumour, and/or informal adult carers (either at individual or family level) of people with a primary malignant brain tumour., Data Collection and Analysis: We followed standard Cochrane methodological procedures for data extraction, management, and analysis. We used GRADE to assess the certainty of the evidence for symptom control, i.e. cognitive function., Main Results: We identified 9748 references from the searches, with 8337 remaining after duplicates were removed. After full-text review, we included one trial. There were no studies of early specialist palliative care interventions or of early, co-ordinated generalist palliative care approaches. The included randomised trial addressed a single symptom area, focusing on early cognitive rehabilitation, administered within two weeks of surgery in a mixed brain tumour population, of whom approximately half had a high-grade glioma. The intervention was administered individually as therapist-led computerised exercises over 16 one-hour sessions, four times/week for four weeks. Sessions addressed several cognitive domains including time orientation, spatial orientation, visual attention, logical reasoning, memory, and executive function. There were no between-group differences in outcome for tests of logical-executive function, but differences were observed in the domains of visual attention and verbal memory. Risk of bias was assessed and stated as high for performance bias and attrition bias but for selective reporting it was unclear whether all outcomes were reported. We considered the certainty of the evidence, as assessed by GRADE, to be very low., Authors' Conclusions: Currently there is a lack of research focusing on the introduction of early palliative interventions specifically for people with primary brain tumours, either as co-ordinated specialist palliative care approaches or interventions focusing on a specific aspect of palliation. Future research should address the methodological shortcomings described in early palliative intervention studies in other cancers and chronic conditions. In particular, the specific population under investigation, the timing and the setting of the intervention should be clearly described and the standardised palliative care-specific components of the intervention should be defined in detail., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectiv E: To summarise current evidence for the utility of interval imaging in monitoring disease in adult brain tumours, and to develop a position for future evidence gathering while incorporating the application of data science and health economics., Methods: Experts in 'interval imaging' (imaging at pre-planned time-points to assess tumour status); data science; health economics, trial management of adult brain tumours, and patient representatives convened in London, UK. The current evidence on the use of interval imaging for monitoring brain tumours was reviewed. To improve the evidence that interval imaging has a role in disease management, we discussed specific themes of data science, health economics, statistical considerations, patient and carer perspectives, and multi-centre study design. Suggestions for future studies aimed at filling knowledge gaps were discussed., Results: Meningioma and glioma were identified as priorities for interval imaging utility analysis. The "monitoring biomarkers" most commonly used in adult brain tumour patients were standard structural MRI features. Interval imaging was commonly scheduled to provide reported imaging prior to planned, regular clinic visits. There is limited evidence relating interval imaging in the absence of clinical deterioration to management change that alters morbidity, mortality, quality of life, or resource use. Progression-free survival is confounded as an outcome measure when using structural MRI in glioma. Uncertainty from imaging causes distress for some patients and their caregivers, while for others it provides an important indicator of disease activity. Any study design that changes imaging regimens should consider the potential for influencing current or planned therapeutic trials, ensure that opportunity costs are measured, and capture indirect benefits and added value., Conclusion: Evidence for the value, and therefore utility, of regular interval imaging is currently lacking. Ongoing collaborative efforts will improve trial design and generate the evidence to optimise monitoring imaging biomarkers in standard of care brain tumour management., Competing Interests: TB, speaker’s bureau for AbbVie and Siemens Healthineers. Craig Buckley, Head of Research and Innovation – Siemens Healthineers GB&I. JC, BrainMiner Founder. Involved in machine learning enterprise and business. JK, involved in enterprise and business. MM, BrainMiner Founder. Involved in machine learning enterprise and business. SO, BrainMiner Founder. Involved in machine learning enterprise and business. MP, received payment for consultancy work from Merck not related to cancer. AW, unrestricted educational grant, Bayer Schering, consultancy work and honoraria not related to cancer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Booth, Thompson, Bulbeck, Boele, Buckley, Cardoso, Dos Santos Canas, Jenkinson, Ashkan, Kreindler, Huskens, Luis, McBain, Mills, Modat, Morley, Murphy, Ourselin, Pennington, Powell, Summers, Waldman, Watts, Williams, Grant and Jenkinson.)

Background: 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., Objectives: 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., Search Methods: 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)., Selection Criteria: 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., 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 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)., Authors' Conclusions: 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., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)