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Abstract Background Patients from socioeconomically disadvantaged backgrounds are underserved in randomised controlled trials, yet they experience a much greater burden of disease compared with patients from socioeconomically advantaged areas. It is crucial to make trials more inclusive to ensure that treatments and interventions are safe and effective in real-world contexts. Improving how information about trials is verbally communicated is an unexplored strategy to make trials more inclusive. This study examined how trials are communicated verbally, comparing consultations involving patients from the most and least socioeconomically disadvantaged areas. Methods Secondary qualitative analysis of 55 trial consultation transcripts from 41 patients, sampled from 3 qualitative studies embedded in their respective UK multi-site, cancer-related randomised controlled trials. Patients living in the most and least socioeconomically disadvantaged areas, defined using English Indices of Multiple Deprivation decile scores, were purposively sampled. Analysis was largely thematic and drew on the constant comparison method. Results Recruiters communicated clinical uncertainty in a similar way for patients living in different socioeconomic areas. Consultations with disadvantaged patients were, on average, half the duration of those with advantaged patients, and tended to involve recruiters providing less in-depth explanations of trial concepts, used phrasing that softened trial arm risks, and described trial processes (e.g. randomisation) using informal or metaphorical phrasing. Disadvantaged and advantaged patients differed in the concerns they expressed; disadvantaged patients voiced fewer concerns and asked fewer questions but were also less likely to be invited to do so by recruiters. Conclusion Interactions about trials unfolded in different ways between patients living in different socioeconomic areas, likely due to both patient- and recruiter-related factors. We present considerations for recruiters when discussing trials with patients from socioeconomically disadvantaged backgrounds, aimed at enhancing trial communication. Future research should examine disadvantaged patients’ and recruiters’ experiences of verbal trial communication to inform guidance that addresses the needs and preferences of underserved groups.

Abstract Background Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur. Results Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two responder subtypes based on longitudinal changes in gene expression. In two thirds of patients, a specific subset of genes is upregulated from primary to recurrence (Up responders), and in one third, the same genes are downregulated (Down responders), specifically in neoplastic cells. Characterization of the responder subtypes indicates subtype-specific adaptive treatment resistance mechanisms that are associated with distinct changes in the tumor microenvironment. In Up responders, recurrent tumors are enriched in quiescent proneural GBM stem cells and differentiated neoplastic cells, with increased interaction with the surrounding normal brain and neurotransmitter signaling, whereas Down responders commonly undergo mesenchymal transition. ChIP-sequencing data from longitudinal GBM tumors suggests that the observed transcriptional reprogramming could be driven by Polycomb-based chromatin remodeling rather than DNA methylation. Conclusions We show that the responder subtype is cancer-cell intrinsic, recapitulated in in vitro GBM cell models, and influenced by the presence of the tumor microenvironment. Stratifying GBM tumors by responder subtype may lead to more effective treatment.

Meningioma are the most common primary brain tumour. Classically, meningioma are phenotypically grouped using the World Health Organisation (WHO) classification system. However, it is now understood that the WHO approach overfits tumours into three grades, resulting in similarly graded tumours displaying phenotypically distinct behaviour. There is a growing body of research investigating the molecular biology of these tumours, including genomic, transcriptomic, metabolomic, proteomic, and methylomic profiling. Such advancements in molecular profiling of meningioma are providing greater accuracy in prognostication of tumours. Furthermore, a clearer understanding of tumour molecular biology highlights potential targets for pharmacotherapies. Currently, the routine application of in-depth tumour molecular analysis is limited, however as it becomes more widely available it will likely result in improved patient care. This review seeks to explore the important developments in meningioma molecular biology, discussed in the context of their clinical importance.

Abstract Brain metastases comprise 40% of all metastatic tumours and breast tumours are among the tumours that most commonly metastasise to the brain, the role that epigenetic gene dysregulation plays in this process is not well understood. We carried out 450 K methylation array analysis to investigate epigenetically dysregulated genes in breast to brain metastases (BBM) compared to normal breast tissues (BN) and primary breast tumours (BP). For this, we referenced 450 K methylation data for BBM tumours prepared in our laboratory with BN and BP from The Cancer Genome Atlas. Experimental validation on our initially identified genes, in an independent cohort of BP and in BBM and their originating primary breast tumours using Combined Bisulphite and Restriction Analysis (CoBRA) and Methylation Specific PCR identified three genes (RP11-713P17.4, MIR124-2, NUS1P3) that are hypermethylated and three genes (MIR3193, CTD-2023M8.1 and MTND6P4) that are hypomethylated in breast to brain metastases. In addition, methylation differences in candidate genes between BBM tumours and originating primary tumours shows dysregulation of DNA methylation occurs either at an early stage of tumour evolution (in the primary tumour) or at a later evolutionary stage (where the epigenetic change is only observed in the brain metastasis). Epigentic changes identified could also be found when analysing tumour free circulating DNA (tfcDNA) in patient’s serum taken during BBM biopsies. Epigenetic dysregulation of RP11-713P17.4, MIR3193, MTND6P4 are early events suggesting a potential use for these genes as prognostic markers.

Discrimination of brain cancer versus non-cancer patients using serum-based attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy diagnostics was first developed by Hands et al with a reported sensitivity of 92.8% and specificity of 91.5%. Cameron et al. then went on to stratifying between specific brain tumour types: glioblastoma multiforme (GBM) vs. primary cerebral lymphoma with a sensitivity of 90.1% and specificity of 86.3%. Expanding on these studies, 30 GBM, 30 lymphoma and 30 non-cancer patients were selected to investigate the influence on test performance by focusing on specific molecular weight regions of the patient serum. Membrane filters with molecular weight cut offs of 100 kDa, 50 kDa, 30 kDa, 10 kDa and 3 kDa were purchased in order to remove the most abundant high molecular weight components. Three groups were classified using both partial least squares-discriminate analysis (PLS-DA) and random forest (RF) machine learning algorithms; GBM versus non-cancer, lymphoma versus non-cancer and GBM versus lymphoma. For all groups, once the serum was filtered the sensitivity, specificity and overall balanced accuracies decreased. This illustrates that the high molecular weight components are required for discrimination between cancer and non-cancer as well as between tumour types. From a clinical application point of view, this is preferable as less sample preparation is required.

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.

Introduction Glioblastoma is the most common malignant primary brain tumour with a median overall survival of 12–15 months (range 6–17 months), even with maximal treatment involving debulking neurosurgery and adjuvant concomitant chemoradiotherapy. The use of postoperative imaging to detect progression is of high importance to clinicians and patients, but currently, the optimal follow-up schedule is yet to be defined. It is also unclear how adhering to National Institute for Health and Care Excellence (NICE) guidelines—which are based on general consensus rather than evidence—affects patient outcomes such as progression-free and overall survival. The primary aim of this study is to assess MRI monitoring practice after surgery for glioblastoma, and to evaluate its association with patient outcomes.Methods and analysis ImagiNg Timing aftER surgery for glioblastoma: an eVALuation of practice in Great Britain and Ireland is a retrospective multicentre study that will include 450 patients with an operated glioblastoma, treated with any adjuvant therapy regimen in the UK and Ireland. Adult patients ≥18 years diagnosed with glioblastoma and undergoing surgery between 1 August 2018 and 1 February 2019 will be included. Clinical and radiological scanning data will be collected until the date of death or date of last known follow-up. Anonymised data will be uploaded to an online Castor database. Adherence to NICE guidelines and the effect of being concordant with NICE guidelines will be identified using descriptive statistics and Kaplan-Meier survival analysis.Ethics and dissemination Each participating centre is required to gain local institutional approval for data collection and sharing. Formal ethical approval is not required since this is a service evaluation. Results of the study will be reported through peer-reviewed presentations and articles, and will be disseminated to participating centres, patients and the public.

Introduction 5-aminolevulinic acid (5-ALA) is a proagent developed for fluorescent-guided surgery for high-grade glioma patients associated with a significant increase in resection conferring survival. 5-ALA was shown to penetrate the blood–brain barrier accumulating in malignant glioma cells with high selectivity, sensitivity and positive predictive value. However, those have yet to be explored aiding diagnosis for tumours of the central nervous system (CNS) other than high-grade gliomas (HGG). No up-to-date systematic review exists reporting the major surgical outcomes and diagnostic accuracy. We sought to conduct a systematic review of the literature summarising surgical outcomes, evaluate the quality of diagnostic accuracy reported in the literature and qualitatively assess the evidence to inform future studies.Methods and analysis We will search electronic databases (Medline, Embase) with subsequent interrogation of references lists of articles reporting the use of 5-ALA for brain tumours other than high-grade glioma adult patients, which also report the extent of resection and/or survival. Prospective and retrospective cohort and case–control studies with more than five patients will be included. Two independent reviewers will screen the abstracts and full articles, with a third reviewer resolving any conflicts. The data will be extracted in a standardised template and outcomes will be reported using descriptive statists. The quality of non-randomised studies will be appraised.Ethics and dissemination The study will summarise the available evidence on the effect of the clinical utility of 5-ALA in achieving resection and improving survival and its diagnostic accuracy for tumours of the CNS other than HGG. The data will be presented nationally and internationally and the manuscript will be published in a peer-reviewed journal. No ethical approvals were needed. The aim is to inform prospective studies minimising reporting bias allowing for more reliable, reproducible and generalisable results. The study has been registered in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.PROSPERO registration numberCRD42021260542.

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

Abstract Background Brain metastases are common in clinical practice. Many clinical scales exist for predicting survival and hence deciding on best treatment but none are individualised and none use quantitative imaging parameters. A multicenter study was carried out to evaluate the prognostic utility of a simple diffusion weighted MRI parameter, tumor apparent diffusion coefficient (ADC). Methods A retrospective analysis of imaging and clinical data was performed on a cohort of 223 adult patients over a ten-year period 2002–2012 pooled from three institutions. All patients underwent surgical resection with histologically confirmed brain metastases and received adjuvant whole brain radiotherapy and/or chemotherapy. Survival was modelled using standard clinical variables and statistically compared with and without the addition of tumor ADC. Results The median overall survival was 9.6 months (95% CI 7.5–11.7) for this cohort. Greater age (p = 0.002), worse performance status (p

Brain metastases are a major clinical problem, and immunotherapy offers a novel treatment paradigm with the potential to synergize with existing focal therapies like surgery and radiosurgery or even replace them in future. The brain is a unique microenvironment structurally and immunologically. The immune response is likely to be crucial to the adaptation of systemic immune modulating agents against this disease. Imaging is frequently employed in the clinical diagnosis and management of brain metastasis, so it is logical that brain imaging techniques are investigated as a source of biomarkers of the immune response in these tumors. Current imaging techniques in clinical use include structural MRI (post-contrast T1W sequences, T2, and FLAIR), physiological sequences (perfusion- and diffusion-weighted imaging), and molecular imaging (MR spectroscopy and PET). These are reviewed for their application to predicting and measuring the response to immunotherapy in brain metastases.

Diagnosing brain cancer is frequently difficult and requires specialist equipment. Here, the authors develop their previous attenuated total reflectance-Fourier transform infrared spectroscopy method and incoporate the use of disposable silicon wafers for diagnosing brain cancer using serum samples.

Objectiv eTo 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.MethodsExperts 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.ResultsMeningioma 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.ConclusionEvidence 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.

Meningeal tumors represent approximately 10–25% of primary brain tumors and occur usually in elderly female patients. Most meningiomas are benign (80–85%) and for symptomatic and/or large tumors, surgery, with or without radiation therapy (RT), has been long established as an effective means of local tumor control. RT can be delivered to inoperable lesions or to those with non-benign histology and for Simpson I–III and IV–V resection. RT can be delivered with photons or particles (protons or carbon ions) in stereotactic or non-stereotactic conditions. Particle therapy delivered for these tumors uses the physical properties of charged carbon ions or protons to spare normal brain tissue (i.e. Bragg peak), with or without or a dose-escalation paradigm for non-benign lesions. PT can substantially decrease the dose delivered to the non-target brain tissues, including but not limited to the hippocampi, optic apparatus or cochlea. Only a limited number of meningioma patients have been treated with PT in the adjuvant or recurrent setting, as well as for inoperable lesions with pencil beam scanning and with protons only. Approximately 500 patients with image-defined or WHO grade I meningioma have been treated with protons. The reported outcome, usually 5-year local tumor control, ranges from 85 to 99% (median, 96%). For WHO grade II or III patients, the outcome of only 97 patients has been published, reporting a median tumor local control rate of 52% (range, 38–71.1). Only 24 recurring patients treated previously with photon radiotherapy and re-treated with PT were reported. The clinical outcome of these challenging patients seems interesting, provided that they presented initially with benign tumors, are not in the elderly category and have been treated previously with conventional radiation dose of photons. Overall, the number of meningioma patients treated or-re-irradiated with this treatment modality is small and the clinical evidence level is somewhat low (i.e. 3b–5). In this review, we detail the results of upfront PT delivered to patients with meningioma in the adjuvant setting and for inoperable tumors. The outcome of meningioma patients treated with this radiation modality for recurrent tumors, with or without previous RT, will also be reviewed.

Objectives Pressures on healthcare systems due to COVID-19 has impacted patients without COVID-19 with surgery disproportionally affected. This study aims to understand the impact on the initial management of patients with brain tumours by measuring changes to normal multidisciplinary team (MDT) decision making.Design A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020.Setting Regional neurosurgical units outside London (as the pandemic was more advanced at time of study).Participants Representatives from all units were invited to collect data on new patients discussed at their MDT meetings during the study period. Each unit decided if management decision for each patient had changed due to COVID-19.Primary and secondary outcome measures Primary outcome measures included number of patients where the decision to undergo surgery changed compared with standard management usually offered by that MDT. Secondary outcome measures included changes in surgical extent, numbers referred to MDT, number of patients denied surgery not receiving any treatment and reasons for any variation across the UK.Results 18 units (75%) provided information from 80 MDT meetings that discussed 1221 patients. 10.7% of patients had their management changed—the majority (68%) did not undergo surgery and more than half of this group not undergoing surgery had no active treatment. There was marked variation across the UK (0%–28% change in management). Units that did not change management could maintain capacity with dedicated oncology lists. Low volume units were less affected.Conclusion COVID-19 has had an impact on patients requiring surgery for malignant brain tumours, with patients receiving different treatments—most commonly not receiving surgery or any treatment at all. The variations show dedicated cancer operating lists may mitigate these pressures.Study registration This study was registered with the Royal College of Surgeons of England’s COVID-19 Research Group (https://www.rcseng.ac.uk/coronavirus/rcs-covid-research-group/).

Background: Insertion of a ventriculoperitoneal shunt to treat hydrocephalus is one of the most common neurosurgical procedures worldwide. Shunt infection affects up to 15% of patients, resulting in long hospital stays, multiple surgeries and reduced cognition and quality of life. Objectives: The aim of this trial was to determine whether or not antibiotic-impregnated ventriculoperitoneal shunts (hereafter referred to as antibiotic shunts) (e.g. impregnated with rifampicin and clindamycin) or silver-impregnated ventriculoperitoneal shunts (hereafter referred to as silver shunts) reduce infection compared with standard ventriculoperitoneal shunts (hereafter referred to as standard shunts). Design: This was a three-arm, superiority, multicentre, parallel-group randomised controlled trial. Patients and a central primary outcome review panel, but not surgeons or operating staff, were blinded to the type of ventriculoperitoneal shunt inserted. Setting: The trial was set in 21 neurosurgical wards across the UK and the Republic of Ireland. Participants: Participants were patients with hydrocephalus of any aetiology who were undergoing insertion of their first ventriculoperitoneal shunt. Interventions: Participants were allocated 1 : 1 : 1 by pressure-sealed envelope to receive a standard non-impregnated, silver-impregnated or antibiotic-impregnated ventriculoperitoneal shunt at the time of insertion. Ventriculoperitoneal shunts are medical devices, and were used in accordance with the manufacturer’s instructions for their intended purpose. Main outcome measures: The primary outcome was time to ventriculoperitoneal shunt failure due to infection. Secondary outcomes were time to failure for any cause, reason for failure (infection, mechanical), types of ventriculoperitoneal shunt infection, rate of infection after first clean (non-infected) revision and health economics. Outcomes were analysed by intention to treat. Results: Between 26 June 2013 and 9 October 2017, 1605 patients from neonate to 91 years of age were randomised to the trial: n = 36 to the standard shunt, n = 538 to the antibiotic shunt and n = 531 to the silver shunt. Patients who did not receive a ventriculoperitoneal shunt (n = 4) or who had an infection at the time of insertion (n = 7) were not assessed for the primary outcome. Infection occurred in 6.0% (n = 32/533) of those who received the standard shunt, in 2.2% (n = 12/535) of those who received the antibiotic shunt and in 5.9% (n = 31/526) of those who received the silver shunt. Compared with the standard shunt, antibiotic shunts were associated with a lower rate of infection (cause-specific hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80) and a decreased probability of infection (subdistribution hazard ratio 0.38, 97.5% confidence interval 0.18 to 0.80). Silver shunts were not associated with a lower rate of infection than standard shunts (cause-specific hazard ratio 0.99, 97.5% confidence interval 0.56 to 1.74). The ventriculoperitoneal shunt failure rate attributable to any cause was 25.0% overall and did not differ between arms. Antibiotic shunts save £135,753 per infection avoided. There were no serious adverse events. Limitations: It was not possible to blind treating neurosurgeons to the ventriculoperitoneal shunt type. The return rate for patient-reported outcomes was low. Limitations to the economic evaluation included failure to obtain Hospital Episode Statistics data from NHS Digital, as per protocol. Reliance on patient-level information and costing systems data mitigated these limitations. Conclusions: Antibiotic shunts have a reduced infection rate compared with standard shunts, whereas silver shunts do not. Antibiotic shunts are cost-saving. Future work: A sample collection has been established that will enable the study of surrogate markers of ventriculoperitoneal shunt infection in cerebrospinal fluid or blood using molecular techniques. A post hoc analysis to study factors related to shunt failure will be performed as part of a future study. An impact analysis to assess change in practice is planned. Trial registration: Current Controlled Trials ISRCTN49474281. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 17. See the NIHR Journals Library website for further project information.

Abstract Background Glioblastoma is the commonest form of malignant brain tumour in adults, affecting 2–3 people per 100,000 per year. Despite current treatment options including surgical resection, radiotherapy and temozolomide chemotherapy, overall survival at 2 years is approximately 27%, with a median survival of 12–14 months. The ketogenic diet (KD) is postulated to work by simulating the metabolic response to fasting by promoting the utilisation of ketones as a primary energy source, and depriving the glycolytic pathways utilised by malignant glioma cells for growth. At present, there is no consensus as to which KD is preferable, with previous case series using different KDs, at different points in the treatment pathway. The aim of this randomised pilot study is to investigate protocol feasibility, tolerability and the impact on patient health and quality of life of two different KDs within an NHS setting. The results of this pilot study will inform which KD will be most deliverable and adhered to by patients in order to test for effectiveness in future trials. Methods A prospective, non-blinded, randomised, pilot study will be undertaken in 12 patients with newly diagnosed glioblastoma treated by surgical resection. Patients will be randomised in a ratio of 1:1, using a permuted block randomisation method to one of two diets; the modified ketogenic diet and the medium chain triglyceride ketogenic diet. Primary data collection will take place 12 weeks after starting the diet and secondary data collection after 12 months. Feasibility will be assessed by retention and recruitment rates, ability to enrol patients prior to starting chemoradiotherapy, dietary compliance and adjustments, ketone levels, glucose levels and intervention time. Patient impact will be assessed through quality of life and food acceptability questionnaires, gastrointestinal side effects and changes to biochemical markers and anthropometric measures, assessed at regular intervals. Discussion The results of this pilot study will be used to inform the feasibility, methodological design and power calculations of future phase III clinical trials investigating the effectiveness of KD as an adjuvant therapy in the management of glioblastoma. Trial registration ISRCTN71665562 and NCT03075514 .

The prevalence of idiopathic intracranial hypertension (IIH), a complex disorder, is increasing globally in association with obesity. The IIH syndrome occurs as the result of elevated intracranial pressure, which can cause permanent visual impairment and loss if not adequately managed. CSF diversion via ventriculoperitoneal and lumboperitoneal shunts is a well-established strategy to protect vision in medically refractory cases. Success of CSF diversion is compromised by high rates of complication; including over-drainage, obstruction, and infection. This review outlines currently used techniques and technologies in the management of IIH. Neurosurgical CSF diversion is a vital component of the multidisciplinary management of IIH.

Aim: We performed a systematic review of the evidence for effectiveness and acceptability of different ketogenic diets (KDs) in the therapeutic management of gliomas. Methods: The search strategy included searches of seven electronic databases. Data extraction and quality assessment were undertaken independently by two authors. Results: No randomized clinical trials were identified. Six studies (n = 39) met the eligibility criteria for this review – all were case series or reports and therefore at high risk of bias. All studies reported overall or progression-free survival; however the effectiveness of KD interventions could not be established. Dietary acceptability was not reported. Conclusion: The effectiveness and acceptability of KDs in the management of gliomas is unknown and high quality randomized controlled trials are needed.