Robert Grant

• MBChB, MD
• Consultant at NHS Lothian

Background Instruments to assess patient-reported outcomes (PRO) should generate high-quality evidence. Reliable PRO evidence is essential to policymakers, in conjunction with outcomes such as survival and radiological response, to understand the net clinical benefit of antitumor treatments. This study aimed to establish the content validity of 215...

Background Glioma are infiltrative primary brain tumours, which despite treatment, lead to a substantial reduction in life expectancy. Seizures are a common symptom of glioma, and have a serious impact on patient health related quality of life (HRQoL). Objective The study aimed to estimate health state utility values for different types of seizure...

Background The challenges and needs of people with brain tumors are complex and unique, particularly—but not limited to—the neurocognitive impacts they experience. These effects are subsequently impactful on their primary caregivers. Evidence suggests people with glioma and their caregivers experience a range of unmet needs in the clinical care set...

BACKGROUND 50-80% of all glioma patients will suffer from seizures during their lifetime. Over half of these patients will have drug resistant seizures. Seizure risk is increased peri-operatively, at tumour progression, and shortly before death. Current guidelines do not support routine use of prophylactic peri-operative anti-epileptic drugs (AED)...

BACKGROUND The needs of people with brain tumours are unique, particularly in terms of neurocognitive impacts, and their subsequent effects on primary caregivers. Evidence suggests that those with brain tumours and their primary caregivers experience unmet needs in the clinical care setting. MATERIAL AND METHODS Semi-structured interviews with peo...

BACKGROUND Glioma patients’ high symptom burden and the poor prognosis of high grade glioma has emphasised quality of survival and overall health-related quality of life (HRQOL) throughout the disease trajectory in clinical trials. Patient-reported outcomes (PROs) allow insight into how investigative treatment affects patients’ perceived functionin...

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 contribu...

Background Most primary brain tumor patients rely on family caregivers for support. Caregiving can be rewarding, but also leads to significant burden from unmet needs. We aimed to: 1) identify and characterize caregivers’ unmet needs; 2) determine associations between unmet needs and wish for support; 3) evaluate acceptability of the Caregiver Need...

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 Inve...

AIMS Glioma, the most common primary brain tumour, has variable survival rates. Existing evidence describes detriment to quality of life from persistent symptoms/side effects, functional loss and feelings of disconnection, particularly in glioblastoma; however, there remains limited focus on the experience of longer-term survivors. This study aimed...

AIMS Trial registration supports unbiased reporting of research studies. Despite inconsistent use globally and sub-optimal completeness, registration is associated with publication of the same outcomes as defined in trial protocols, though these are not necessarily reported in published results. In the core outcomes in brain tumour trials (COBra) s...

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 o...

Background Gliomas are the commonest form of primary brain tumour, accounting for 80% of malignant brain tumours. Gliomas represent a heterogeneous group of cancers with variable outcomes, traditionally graded from I to IV (least to most aggressive). The poor prognosis of some glioma patients and high symptom burden has led to a growing emphasis on...

Background Differentiating secondary headache from primary headache on history alone can sometimes be difficult. Headache “plus” other subtle cognitive features improves prediction. Patients and relatives may attribute subtle cognitive or behavioural changes to other causes (e.g. anxiety, low mood). Sematic verbal fluency - “how many animals can yo...

Background Trials of approved medications for new indications are becoming increasingly common (repurposing). SPRING – Seizure Prophylaxis IN Glioma is a trial of prophylactic Levetiracetam in adults without prior history of seizure versus no AED. Significant delays were encountered in the set up phase. Issues Legal contracts between Sponsor and N...

Background It is not known whether imaging at pre-specified time points after glioma diagnosis and treatment leads to better outcomes than triggered imaging performed in response to new or worsening symptoms. Objectives To systematically review the effect of different imaging strategies on health and economic outcomes for adults with cerebral glio...

Background Patients with brain tumours often present with non-specific symptoms. Correctly identifying who to prioritise for urgent brain imaging is challenging. Brain tumours are amongst the commonest cancers diagnosed as an emergency presentation. A verbal fluency task (VFT) is a rapid triage test affected by disorders of executive function, lang...

Background Neurocognitive impairments are common among brain tumour patients, and may impact patient’s awareness of performance in instrumental activities in daily life (IADL). We examined differences between patient- and proxy-reported assessments of the patient’s IADL, and whether the level of (dis)agreement is associated with neurocognitive impa...

BACKGROUND Most primary brain tumour patients rely on informal caregivers (i.e. family members or friends) for practical and emotional support. While caregiving can be rewarding, it may lead to significant burden. To develop support it is therefore vital to distinguish between unmet needs, and an actual wish for support. Study aims: 1) identify the...

Aims Patients with brain tumours and headache commonly have poorer cognitive skills, either overtly or covertly, when cognitively tested. Cognitive changes reflect, tumour mass, fronto-temporal location or hydrocephalus, Previous work has demonstrated that the “semantic Verbal Fluency Test (SVFT) -“How many animals can you think of in a minute?” is...

BACKGROUND Most primary brain tumour patients rely on informal caregivers (i.e. family members or friends) for practical and emotional support. While caregiving can be rewarding, it also commonly leads to significant burden. In developing support for caregivers, it is vital to distinguish between caregivers’ unmet needs, and their actual wish for s...

BACKGROUND Neurocognitive deficits are common among brain tumour patients, and may impact on patient awareness of deficits in instrumental activities in daily life (IADL). This study aimed to examine differences between patient-reported and proxy-reported assessments of the patient’s performance of IADL, and whether the level of (dis)agreement is as...

Background Glioma patients may experience behavioral and personality changes (BPC), negatively impacting their lives and that of their relatives. However, there is no clear definition of BPC for adult glioma patients, and here we aimed to determine which characteristics of BPC are relevant to include in this definition. Methods Possible characteri...

Purpose Being able to function independently in society is an important aspect of quality of life. This ability goes beyond self-care, requires higher order cognitive functioning, and is typically measured with instrumental activities of daily living (IADL) questionnaires. Cognitive deficits are frequently observed in brain tumour patients, however...

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...

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 statu...

Aims: To evaluate the frequency of impairment on semantic verbal fluency (SVF) test in patients with a new brain tumour prior to neurosurgery and to examine scores across symptom presentations. Methods: This is a secondary analysis of clinical, cognitive and capacity data from a prospective study of consent in patients with newly diagnosed brain tu...

Background When GPs suspect a brain tumour, a referral for specialist assessment and subsequent brain imaging is generally the first option. NICE has recommended that GPs have rapid direct access to brain imaging for adults with progressive sub‐acute loss of central nervous function; however, no studies have evaluated the cost‐effectiveness. Metho...

BACKGROUND Fatigue is common and disabling for brain tumour patients. We studied the feasibility of two innovative lifestyle coaching interventions for high fatigue. METHODS Multi-centre phase II feasibility RCT (ISRCTN17883425). Adult primary brain tumour outpatients reporting significant fatigue (Brief Fatigue Inventory [BFI] score 4+), were ran...

BACKGROUND BT-LIFE is a multi-centre RCT of novel lifestyle coaching treatments for fatigued brain tumour patients. To our knowledge it is also the first example of ‘multi-sectoral research’ to combine healthcare, private, and charity sectors in this population. To maximise learning, the trial team devised a structured reflection opportunity to ask...

BACKGROUND Most brain tumour patients report clinically significant fatigue. Here, we aimed to explore patients’ views of the experience, acceptability and usefulness of participating in a trial of novel lifestyle interventions for fatigue. METHODS Qualitative sub-study within the ‘BT-LIFE’ multi-centre phase II RCT (submitted separately). Fatigue...

BACKGROUND Meningioma is the commonest primary brain tumour. 70% of patients are seizure-free at presentation, but approximately 12% will have seizures within 12 months of surgery. Seizures impact quality of life. Neurosurgeons administer prophylactic anti-epileptic drugs (AED) to prevent seizures despite a lack of evidence to support this. A meta-...

Background: Brain tumours are recognised as one of the most difficult cancers to diagnose because presenting symptoms, such as headache, cognitive symptoms, and seizures, may be more commonly attributable to other, more benign conditions. Interventions to reduce the time to diagnosis of brain tumours include national awareness initiatives, expedit...

Background Brain tumor patients are at high risk of impaired medical decision-making capacity (MDC), which can be ethically challenging as it limits their ability to give informed consent to medical treatments or participation in research. The European Association of Neuro-Oncology Palliative Care Multidisciplinary Taskforce performed a systematic...

Objective To evaluate the effectiveness and tolerability of lacosamide added to one or two antiepileptic drugs (AEDs) in the treatment of patients with brain tumor–related epilepsy (BTRE), and to evaluate patients’ global impression of change and quality of life (QoL). Methods This was a prospective, multicenter, single‐arm, noninterventional stud...

Background: A glioblastoma is a fatal type of brain tumour for which the standard of care is maximum surgical resection followed by chemoradiotherapy, when possible. Age is an important consideration in this disease, as older age is associated with shorter survival and a higher risk of treatment-related toxicity. Objectives: To determine the mos...

Purpose: To determine the prevalence and predictors of fatigue in clinically stable primary brain tumor patients, we used objective and subjective measures and a cross-sectional design. Methods: Eighty-five brain tumor patients completed self-report measures of fatigue, sleep disturbance, mood and growth hormone deficiency. Objective measures of sl...

BACKGROUND Glioma patients may experience behavioral and personality changes (BPC), which have a negative impact on the lives of both brain tumor patients and their relatives. The extent of BPC is currently unknown, and it is unclear if available assessment tools cover all aspects of BPC that are relevant for glioma patients. This study aimed to de...

BACKGROUND Data on the use of lacosamide (LCM) for the treatment of brain tumor-related epilepsy (BTRE) are limited. The objective of this study was to evaluate the effectiveness and tolerability of LCM added to 1 or 2 antiepileptic drugs (AEDs) in the treatment of patients with epilepsy due to low-grade primary brain tumor. MATERIAL AND METHODS P...

BACKGROUND In brain tumour patients, impairments in every day functioning can impact quality of life, and are therefore an important outcome in both clinical trials and practice. One way to measure every day functioning is with an activities of daily living (ADL) questionnaire. Instrumental ADL (IADL) are the cognitively more complex activities, th...

Background: Brain tumour patients see their primary care doctor on average three or more times before diagnosis, so there may be an opportunity to identify 'at risk' patients earlier. Suspecting a brain tumour diagnosis is difficult because brain tumour-related symptoms are typically non-specific. Methods: We explored the predictive value of ref...

Background: Gliomas are brain tumours arising from glial cells with an annual incidence of 4 to 11 people per 100,000. In this review we focus on gliomas with low aggressive potential in the short term, i.e. low-grade gliomas. Most people with low-grade gliomas are treated with surgery and may receive radiotherapy thereafter. However, there is con...

Objectives To evaluate the utility of different symptoms, alone or combined, presented to primary care for an adult brain tumour diagnosis. Design and setting Matched case-control study, using the data from Clinical Practice Research Datalink (2000–2014) from primary care consultations in the UK. Method All presentations within 6 months of the in...

In 2016, the WHO incorporated molecular markers, in addition to histology, into the diagnostic classification of central nervous system (CNS) tumours. This improves diagnostic accuracy and prognostication: oligo-astrocytoma no longer exists as a clinical entity; isocitrate dehydrogenase (IDH) mutant and 1p/19q co-deleted oligodendroglioma is a smal...

Purpose of Review Informed consent is the integral part of good medical practice in patients with brain tumours. Capacity to consent may be affected by the brain disorder or its treatment. We intend to draw upon the current neuro-oncology literature to discuss the influence intracranial tumours have upon patients’ capacity to consent to treatment a...

Objectives There is no consensus regarding the need for prophylactic anti-epileptic drug (AED) in seizure-naive newly-diagnosed glioma patients. Data regarding prophylactic AED use are scant and inconclusive from older, small studies that enrolled patients with brain metastases, benign tumours and gliomas. A definitive randomised controlled trial (...

Objectives To assess whether time to diagnosis influenced surgical procedure and survival in primary malignant brain tumours Design Retrospective cohort study of adult patients newly diagnosed with a primary intra-cerebral tumour April 2010 – March 2015 referred to neuro-oncology centre in South-East Scotland Subjects 400 patients with primary ma...

Objectives Utility of a simple 1 min cognitive screening tool, verbal fluency test, as a potential risk assessment tool for GPs for a suspected brain tumour. Design Case-control study; patients with new diagnosis of brain tumour with a history of headache and patients referred for direct-access-CT for headache without a brain tumour. Subjects 102...

Initial symptomatic management aimed at reducing oedema and treating seizures in brain tumour patients, at an appropriate dose and for an appropriate duration, will produce more benefits than harms.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the most effective and best-tolerated approaches for the treatment of elderly people with newly diagnosed glioblastoma. To summarise current evidence for the incremental resource use, utilities, costs and cost-effectiveness associated with the diffe...

Initial medical management of glioma will depend on distinguishing symptoms related to the direct effects of the tumour, from those that are secondary to the stress or recurrence of a pre-existing psychological illness, and symptoms that are related to medication. The cause of symptoms may vary with time, e.g. headache from raised intracranial pres...

Background: This is an updated version of the original Cochrane Review published in September 2014. The most common primary brain tumours in adults are gliomas. Gliomas span a spectrum from low to high grade and are graded pathologically on a scale of one to four according to the World Health Organization (WHO) classification. High-grade glioma (H...

BACKGROUND We have previously published a Cochrane meta-analysis of the efficacy of anti-angiogenic therapy (AAT) in high grade glioma (HGG) in 2014. Since this time, a number of key trials have been published. An updated meta-analysis was performed to account for these new results. METHODS The primary analysis was to evaluate the pooled overall s...

Patients with brain tumors often have subtle cognitive change, which may go unnoticed by patient and family doctor. This may result in delays in diagnosis. We studied the relationship between first and subsequent symptoms and semantic verbal fluency test (SVFT), a quick cognitive screening test. (Normal median SVFT for 60–79 age range who have 12 y...

INTRODUCTION There is no consensus regarding the utility of prophylactic anti-Epileptic Drugs (AED) given to patients with supratentorial glioma before surgery, who have not had seizures. Newer AEDs have fewer adverse effects but their efficacy in preventing new onset seizures remains to be proven. In 2016, we surveyed all members of the Society of...

Background Early diagnosis of brain tumours is one of the top 10 research priorities. Early symptoms are often non-specific such as headache or cognitive/personality changes which will not cause high enough suspicion of a brain tumour for a General Practitioner (GP). As a result, there are often a delay in patient presentation to primary care, refe...

Background It is difficult to identify patients who may have a brain tumour based on symptoms alone. Previous work in a group of pre-operative brain tumour patients identified an association between poor verbal fluency score and incapacity. We examined verbal fluency in an unselected cohort of brain tumour patients presenting for surgery to describ...

Background Delays to brain tumour diagnosis impacts on patient well-being, and may affect available treatment options and patient outcomes. Promoting earlier diagnosis is one of the top 10 clinical research priorities for the UK neuro-oncology community. Understanding the pathway from symptom onset to treatment, and how this varies between patients...

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the long-term neurocognitive and other side effects of radiotherapy (with or without chemotherapy) compared with no radiotherapy, or different types of radiotherapy, among people with glioma (where 'long-term' is defined as at least two years after d...

Background Direct Access Cerebral Imaging (DACI) from Primary Care has been recommended by NICE for patients with symptoms suspicious of cancer. Aim We analysed the predictive value of the NICE (2005) and Kernick referral guidance for suspicion of brain tumour in a real-world setting Method DACI referrals from Lothian-based GPs (31/3/2010 to 1/4/...

The Response Assessment in Neuro-Oncology-Patient-Reported Outcome (RANO-PRO) working group is an international multidisciplinary collaboration that provides guidance on the use of patient-reported outcome (PRO) measures in clinical trials and practice for adult patients with brain tumours. Findings from both PROs and traditional outcome measures,...

Background: Brain tumours often present with varied, non-specific features with other diagnoses usually being more likely. Objective: To examine how different symptoms and patient demographics predict variations in time to brain tumour diagnosis. Methods: We conducted a secondary analysis of brain tumour cases from National Audit of Cancer Dia...

Guidance to General Practitioners on referral for direct-access brain imaging, based on levels of risks for CNS malignancy (red/orange/yellow) are proposed. However, the effect of such guidance upon referral behaviour is unknown. We reviewed all Open-Access-Computed- Tomography (OACT) referrals for possible CNS malignancy from Lothian-based GPs for...

The National Cancer Research Institute (NCRI) is a partnership of charity and government research funders whose purpose is to improve health and quality of life by accelerating progress in cancer-related research through collaboration. Under this umbrella, the NCRI Brain Tumor Clinical Studies Group is focused on improving clinical outcomes for adu...

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the effectiveness and tolerability of dietary intervention with the ketogenic diet (KD) for the management of brain and spinal cord tumours, including the effect on brain-tumour related epilepsy. © 2017 The Cochrane Collaboration. Published by John W...

Patients with glioma present with complex palliative care needs throughout their disease trajectory. The life-limiting nature of gliomas and the presence of specific symptoms related to neurological deterioration necessitate an appropriate and early palliative care approach. The multidisciplinary palliative care task force of the European Associati...

Introduction: Epilepsy is associated with adverse effects on cognition and psychological functioning. Polytherapy and poor seizure control have been associated with poor cognition. Little research has been carried out on the impact of epileptic seizures and anti-epileptic drugs (AED) on cognition in patients with brain tumours (BT). We have compare...

Glioma patients are not only confronted with the diagnosis and treatment of cancer, but often experience disease-specific symptoms that greatly affect everyday life. Common symptoms among patients include motor dysfunction, sensory loss, seizures, cognitive deficits, changes in behaviour and personality, mood issues, and fatigue. This review focuse...

Aim Patients with headaches related to brain tumours often have unrecognised cognitive problems. We examined the semantic verbal fluency (SVF) –“animals named in one minute”– in patients admitted to neurosurgical wards as a potential screening test for GPs to assist selection of patients with headache for early referral. Methods Secondary analysis...

Background We have previously published ¹ the outcomes of patients treated in our unit from the era before pre-chemoRT so this study was conducted to investigate how many patients were deemed suitable for this treatment and the impact on survival Methods Using the Edinburgh Cancer Centre database, all individuals with a biopsy proven GBM seen betw...

Background Patients initially presenting with headaches or cognitive problems related to a brain tumor often have a delayed recognition and diagnosis. Preserved cognition is considered to be a prognostic factor of survival and deficits can negatively influence daily functioning, compromise patients’ and carers’ health-related quality of life (QoL)....

Opinion statement: Neurocognitive deficits are common with brain tumors. If assessed at presentation using detailed neurocognitive tests, problems are detected in 80 % of cases. Neurocognition may be affected by the tumor, its treatment, associated medication, mood, fatigue, and insomnia. Interpretation of neurocognitive problems should be conside...

This chapter describes the best available medical, surgical and oncological evidence for treatment of primary and metastatic brain tumours and the methodological pitfalls of interpreting imaging response and progression. Symptomatic management with steroids and anticonvulsants at the correct dose in the appropriate setting remain crucially importan...

Seizures are a well-recognized symptom of primary brain tumors, and anticonvulsant use is common. This paper provides an overview of epilepsy and the use of anticonvulsants in glioma patients. Overall incidence and mechanisms of epileptogenesis are reviewed. Factors to consider with the use of antiepileptic drugs (AEDs) including incidence during t...

Aims To identify the frequency and severity of fatigue in adults with cerebral glioma, and its association with anti-epileptic drugs (AED). Methods Cross-sectional study. Stable glioma patients attending Edinburgh Neuro-Oncology clinic completed a fatigue Visual Analogue Scale (range 0-100mm, “high” >=60 mm). AED type and dose were recorded. Result...

INTRODUCTION: Many clinical questions about brain and spinal cord tumours remain unanswered. Objectives of the Neuro-Oncology Priority Setting Partnership (PSP) were: To identify the top 10 treatment uncertainties in diagnosis and management of primary central nervous system (CNS) tumours; To highlight the necessity of a brain tumour community coll...

BACKGROUND: Fatigue is the most common symptom reported by primary brain tumour patients; causes are multi-factorial. The aim of the study was to further explore fatigue in relation to co-occurring symptoms. METHODS: A single-centre cross-sectional prospective study design was used. Inclusion criteria were: histological diagnosis of a primary brain...

INTRODUCTION: The widely used antiepileptic drug (AED) Levetiracetam has previously been associated with behavioural changes. We hypothesised that patients taking Levetiracetam would experience higher levels of fatigue than patients on other AEDs. METHOD: Secondary analysis of a prospective observational study. Clinically stable adult outpatients w...

INTRODUCTION: The James Lind Alliance (JLA) supports the NIHR to develop research evidence. Chief Medical Officer Dame Sally Davies has said: “Bringing patients and clinicians together to prioritise treatment uncertainties, is at the heart of the NIHR.” A Neuro-Oncology Priority Setting Partnership was established following JLA guidelines to identi...

Background: This is an updated version of the original Cochrane review published in Issue 3 (Lee 2012) on patient positioning (mobilisation) and bracing for pain relief and spinal stability in adults with metastatic spinal cord compression.Many patients with metastatic spinal cord compression (MSCC) have spinal instability, but their clinician has...

Patients with primary intrinsic brain tumors can experience neurological, cognitive, and psychiatric symptoms that greatly affect daily life. In this review, we focus on changes in personality and behavior, mood issues, hallucinations, and psychosis, because these are either difficult to recognize, to treat, or are understudied in scientific litera...

Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. To assess the effectiveness of interventions for preventing or ameliorating cognitive...

Appendix S2. Study characteristics.

Appendix S3. Collated gene therapies.

Appendix S4. Study quality scores.

Appendix S5. Number of animals per group needed to achieve a set statistical power.

Appendix S1. References used in systematic review.

INTRODUCTION: The development of new therapeutics is often characterised by promising animal research that fails to translate into clinical efficacy; this holds for the development of gene therapy in glioma. We set out to test the hypothesis that this is because of limitations in the internal and external validity of studies reporting the use of ge...

INTRODUCTION: Fatigue is unusual daytime tiredness not relieved by sleep. It is common and with mixed aetiology in glioma. Annual fatigue assessment in stable patients with glioma is being trialled through a ‘symptoms MDM’ METHOD: Patients aged >18years, diagnosed with a glioma that was clinically stable, and had completed a fatigue study, were off...

Chemotherapy Induced Peripheral Neuropathy (CIPN) is a disabling pain condition resulting from chemotherapy for cancer. Severe acute CIPN may require chemotherapy dose reduction or cessation. There is no effective CIPN prevention strategy; treatment of established chronic CIPN is limited, and the prevalence of CIPN is not known. Here we used system...