David A Walker

David A Walker
University of Nottingham | Notts · Division of Child Health

B Med Sci BM BS FRCP FRCPCH

About

272
Publications
28,934
Reads
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5,053
Citations
Additional affiliations
April 1990 - present
University of Nottingham
Position
  • Co-Director
Description
  • The research centre was established in 1997 and has four main themes, molecular, application of imaging, optimising drug delivery systems, and avoiding harm to the brain.www.cbtrc.org

Publications

Publications (272)
Conference Paper
Aims The incidence of childhood cancer has risen by 15% and is the leading illness cause of death in children and young people (CYP). Childhood cancer poses a diagnostic dilemma to clinicians due to the non-specificity of symptoms, yet no stand-alone paediatric clinical guidance exists to aid decision making.Although the overall five-year survival...
Conference Paper
Aims Childhood soft tissue sarcomas (STS) can develop in various anatomical locations, which differs according to age. The wide range of potential signs or symptoms make early recognition difficult. Time to diagnosis (TTD) of childhood STS has a significant independent association with survival and is associated with increased treatment-related mor...
Article
BACKGROUND: There is currently no method for evaluating drug distribution and tumour coverage using the convection-enhanced drug delivery (CED) technique in diffuse midline glioma of the pons (previous DIPG). AIMS: To determine an imaging protocol that can be used to assess the distribution of infusate in children with DIPG treated with CED of carb...
Article
BACKGROUND: The Nottingham-Liverpool risk stratification tool for predicting post-operative cerebellar mutism syndrome (CMS) requires further refinement. Previous smaller studies identified tumours arising in cerebellar hemispheres (CH+ve) as very low risk and proposed that larger sagittal dimensions may be associated with a higher CMS risk. METHOD...
Article
Children's brain tumours are the biggest cancer killer in children and young adults. Several techniques, such as intra-cerebrospinal fluid chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems, electric field therapy, and intra-arterial and intra-nasal chemotherapy, have the potenti...
Article
Full-text available
Introduction Childhood cancer is diagnosed in 400 000 children and young people (CYP) aged 0–19 years worldwide annually. In the UK, a child’s cumulative cancer risk increases from 1 in 4690 from birth to aged 1, to 1 in 470 by age 15. Once diagnosed, access to treatments offers survival to adulthood for over 80%. Tumour diagnoses are at a later st...
Article
BACKGROUND There is currently no method for evaluating drug distribution and tumour coverage using the convection-enhanced drug delivery (CED) technique in Diffuse Intrinsic Pontine Glioma (DIPG). AIMS To determine an imaging protocol that can be used to assess the distribution of infusate in children with DIPG treated with CED of carboplatin and...
Article
INTRODUCTION Children's brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children, including intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electr...
Article
Full-text available
Background The COVID-19 pandemic led to changes in patterns of presentation to emergency departments. Child health professionals were concerned that this could contribute to the delayed diagnosis of life-threatening conditions, including childhood cancer (CC) and type 1 diabetes (T1DM). Our multicentre, UK-based service evaluation assessed diagnost...
Article
Aims Children's brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children. These include intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electric f...
Conference Paper
Background Child Cancer Smart (https://www.cclg.org.uk/childcancersmart) is a UK public and professional awareness campaign aiming to raise awareness of the symptoms and signs of children, teenagers and young adult (CTYA) cancers. In seeking evidence for the campaign to enhance public and professional awareness, a series of systematic literature re...
Conference Paper
Background In seeking evidence for the Child Cancer Smart (https://www.cclg.org.uk/childcancersmart) campaign to enhance public and professional awareness of children, teenagers and young adult (CTYA) cancers, a series of systematic literature reviews of symptomatology of common cancer clusters of childhood are being conducted to synthesis evidence...
Conference Paper
Full-text available
Background The COVID-19 pandemic led to changes in patterns of presentation to Emergency Departments. Child health professionals were concerned that this could contribute to the delayed diagnosis of life-threatening conditions, including childhood cancer (CC) and type 1 diabetes (T1DM). Objectives Our multicentre, UK-based service evaluation asses...
Article
Background Brain tumours are the most common solid tumours in childhood. Half of these tumours occur in the posterior fossa, where surgical removal is complicated by the risk of cerebellar mutism syndrome, of which postoperative speech impairment (POSI) is a cardinal symptom, in up to 25% of patients. The surgical approach to midline tumours, mostl...
Article
Full-text available
INTRODUCTION Brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the outlook for these children, including intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems, electric field therapy, and intr...
Article
Full-text available
Introduction Brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children. These include ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electric field therapy, as well as in...
Article
PurposeEffective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood–brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical exp...
Article
Full-text available
BACKGROUND The HRQoL of survivors of childhood brain tumour is significantly reduced into adulthood but is not systematically assessed. In the UK, referral for appropriate support is often reactive rather than proactive. We developed KLIK, the online Dutch platform, for use to enable the systematic assessment of HRQoL in the UK NHS using patient-re...
Article
Full-text available
PURPOSE Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical ex...
Article
Full-text available
BACKGROUND Childhood brain tumours and their treatment can reduce health-related quality of life (HRQoL) and cause anxiety and depression, withdrawal, and social isolation. Improved communication within outpatient consultations may allow early identification and treatment of these issues. We explored family communication needs in survivors of child...
Conference Paper
Aims To assess public awareness of the risks and symptoms of cancer in children and young adults under 18 in Great Britain and compare them with the published data where 60–94% of adults are aware of their cancer risks and symptoms. Methods A face-to-face, computer-assisted opinion survey was conducted by Ipsos MORI. The population-based sample in...
Article
Full-text available
Purpose: Posterior fossa brain tumours (PFT) and their treatment in young children are often associated with subsequent cognitive impairment. However, reported follow-up periods rarely exceed 10 years. This study reports very long-term cognitive consequences of surviving an early childhood PFT. Methods: 62 adult survivors of a PFT, ascertained f...
Article
Full-text available
Background: The aim of the project was to identify risk factors associated with visual progression and treatment indications in pediatric patients with Neurofibromatosis type 1 associated optic pathway gliomas (NF1-OPG). Methods: A multi-disciplinary expert group consisting of ophthalmologists, pediatric neuro-oncologists, neurofibromatosis spec...
Article
Key challenges hindering the clinical translation of the use of Nanoparticles (NP) for delivery of drugs to tumours are inadequate drug loading and premature drug release. This study focussed on understanding the conditions required to produce nanoparticles that can reach their target site with sufficient drug loading and drug retention for effecti...
Article
Full-text available
Optic Pathway Glioma (OPG) is a relatively common brain tumour in childhood; however, there is scarce understanding of neuropsychological sequelae in these survivors. In this study, 12 children with diagnosis of OPG before 6 years of age received a comprehensive standardised assessment of visual perception, general intelligence and academic achieve...
Article
Background: Management of unresectable pediatric low-grade glioma and glioneuronal tumor (LGG/LGGNT) is controversial. There are no validated prognostic features to guide use of radiation therapy (RT). Our study aimed to identify negative prognostic features in patients treated with RT using clinicopathologic and molecular data and validate these...
Article
Full-text available
Background Survivors of childhood brain tumors or other acquired brain injury (ABI) are at risk of poor health-related quality of life (HRQoL); its valid and reliable assessment is essential to evaluate the effect of their illness on their lives. The aim of this review was to critically appraise psychometric properties of patient-reported outcome m...
Article
Full-text available
Objective The provision of rehabilitation services after childhood brain tumour has not been established, despite a recent parliamentary call for urgent action. This service evaluation aimed to determine what specialist paediatric neuro-oncology rehabilitation services were available across the UK at the time of the surveys and whether the needs of...
Article
INTRODUCTION The brain tumour community has seen significant progress in the discovery of new therapeutic targets and anticancer drugs. Unfortunately, advances in how to deliver drugs to the brain lag behind. The blood-brain barrier restricts the entry of many small-molecule drugs and nearly all large molecule drugs that have been developed to trea...
Article
Background HeadSmart, a public and professional awareness campaign, was launched to enhance awareness of brain tumour symptomatology identified in the Royal College of Paediatrics and Child Health, National Institute for Health and Care Excellence–accredited guideline. Quality improvement data showed a reduction in diagnostic interval nationally. T...
Article
Background In diffuse intrinsic pontine glioma (DIPG) drug resistance is in part due to inadequate penetration of blood-brain barrier (BBB) by systemically administered drugs. Convection-enhanced drug delivery (CED) techniques have been established to bypass BBB. Trial design to measure efficacy requires evidence to justify power calculation. Aims...
Article
INTRODUCTION: In diffuse intrinsic pontine glioma (DIPG) drug resistance is in part due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered drugs. Convection enhanced drug delivery (CED) techniques have been established to bypass the BBB. Trial design to measure efficacy requires evidence to justify a power calcu...
Article
Objective The provision of rehabilitation services after childhood brain tumour has not been established, despite a recent parliamentary call for urgent action. This service evaluation aimed to determine what specialist paediatric neuro-oncology rehabilitation services were available across the UK at the time of the surveys and whether the needs of...
Article
Full-text available
We describe a 20 month old boy with neuro-fibromatosis type 1 (NF-1) who presented with diencephalic syndrome due to a large hypothalamic tumour and developed massive necrosis after chemotherapy associated with severe encephalopathy. We report this case because of rapid progression of presenting symptoms, the rare association with diencephalic synd...
Conference Paper
Full-text available
BACKGROUND The quality of life (QoL) of children and adolescents treated for brain tumours is significantly impaired into adulthood but is not systematically screened by methods appropriate to these patients. In the UK, referral of them for appropriate support is often reactive rather than proactive. We are developing and testing KLIK, an online pl...
Article
Full-text available
Brain tumours are the most challenging cancers in relation to diagnosis, treatment and outcome. Under normal physiological conditions, brain cells metabolise glucose for energy. If glucose deprived they instead metabolise ketone bodies (KBs). Mitochondrial defects in brain tumours obviate this metabolic flexibility resulting in glucose dependence....
Article
INTRODUCTION Neurofibromatosis type 1 (NF1) is commonly associated with optic pathway gliomas (OPG) in childhood. Data on natural history are lacking and clinical trials of chemotherapy, so far, have not reported visual outcomes. In the 2014 SIOPE NF1-OPG Nottingham Workshop a convenience cohort was assembled and studied to inform a consensus on im...
Conference Paper
Full-text available
INTRODUCTION 60% of childhood brain tumour survivors suffer disability due to prolonged pre-diagnostic intervals with raised intra-cranial pressure (50%) and the risk of visual impairment (<6%); sight threatening visual pathway glioma (VPG); post-operative cerebellar mutism syndrome (CMS) affecting up to 30% of cerebellar tumour patients, and the c...
Article
INTRODUCTION Public and professional concern about delays in diagnosis of childhood brain tumours led to a clinical guideline and HeadSmart campaign to raise awareness of early features. For outcome evaluation, data on total diagnostic intervals (TDI) and awareness was collected. We aim to report the most recent TDI, identify the subgroup(s) with l...
Article
Assessment of basic sensory, cognitive, and motor functions is fundamental for neuropsychological profiling of pediatric patients with brain tumor. Neuropsychological profiling is used to determine extent of functional capacity, pre and post treatment, and in monitoring progression against typical development over time, and in response to intervent...
Article
INTRODUCTION There is an urgent need to expedite the development of new or repurposed drugs for children’s cancer. An additional challenge in the developing brain is to ensure the drug is delivered to the tumour at therapeutic and non-toxic concentrations for sufficient duration to achieve the biological effect. Children’s brain tumours account for...
Article
INTRODUCTION The HeadSmart campaign has been associated with reducing median total diagnostic interval of childhood brain tumours in UK from 14.4 weeks to 6.5 weeks with a new aim of 4 weeks. In 2013, only 26% of family clinicians were aware of the campaign. We conducted a year-long project in collaboration with Royal College of General Practitione...
Article
Poor CNS penetration by cancer drugs limits their application in sensitive brain tumours such as medulloblastoma. An alternative approach, delivering drugs directly to residual tumour using nanoparticulate delivery systems (NPDS) could reduce some of these problems. The main challenges hindering the clinical translation of the use of NPDS for local...
Article
Survivors of paediatric Optic Pathway Glioma (OPG) experience varying degrees of visual impairment. Yet sparse research has examined the impact of brain damage and the resulting vision loss on cognitive development and scholastic progression, and to date, no studies have investigated potential compensatory mechanisms and strategies in auditory func...
Article
Paediatric optic pathway glioma (OPG) and its treatment often result in some degree of sight loss, ranging from mild deterioration to total blindness, in one or both eyes. Residual sight has been widely described through key ophthalmological measures (visual acuity, visual fields, and colour vision), but little is known about more complex processes...
Article
Full-text available
We demonstrated the pattern in presentation of primary intracranial tumors in a population-based cohort of patients aged 0-24 years identified from the National Cancer Registry for England, using linked medical records from primary care and hospitals. We used generalized additive models to estimate temporal changes in presentation rates. Borderline...
Article
Full-text available
Purpose Epileptic seizures complicate the management of childhood brain tumours. There are no published standards for clinical practice concerning risk factors, treatment selection or strategies to withdraw treatment with antiepileptic drugs (AED). Method we undertook a case note review of 120 patients with newly diagnosed brain tumours, referred...
Article
Full-text available
Background: Despite previous identification of pre-operative clinical and radiological predictors of post-operative paediatric cerebellar mutism syndrome (CMS), a unifying pre-operative risk stratification model for use during surgical consent is currently lacking. The aim of the project is to develop a simple imaging-based pre-operative risk scori...
Article
Full-text available
Despite the fact that they are not typically life-threatening, low-grade gliomas (LGGs) remain a significant clinical challenge in pediatric neuro-oncology due to comorbidities associated with these tumors and/or their treatments, and their propensity to multiply recurs. LGGs, in total the most common brain tumors arising in childhood, can often be...
Article
INTRODUCTION Whilst there is an urgent need to expedite the development of new or repurposed drugs for children’s cancer, the additional challenge in the developing brain is to ensure the drug is delivered to the tumour at therapeutic and non-toxic concentrations for sufficient duration to achieve the biological effect. This is the necessary focus...
Chapter
CNS tumors are least likely to present during adolescence, when they do, their clinical presentation is enmeshed with the young person’s physical, psychological, educational, and social development. The population incidence of the different tumor types highlights the transition from “childhood type” to “adult type” and identifies those driven by ad...
Article
Despite the fact that they are not typically life-threatening, low-grade gliomas (LGGs) remain a significant clinical challenge in pediatric neurooncology due to co-morbidities associated with these tumors and/or their treatments, and their propensity to multiply recur. LGGs, in total the most common brain tumors arising in childhood, can often bec...
Article
Full-text available
Background: The use of chemotherapy to manage newly diagnosed low grade glioma (LGG) was first introduced in the 1980s. One randomised trial has studied two- versus four-drug regimens with a duration of 12 months of treatment after resection. Methods: Within the European comprehensive treatment strategy for childhood LGG, the International Socie...
Conference Paper
INTRODUCTION: A consensus survey involving 98 multi-disciplinary specialists for the first survey (10 cases) and 46 for the second survey (15 cases) in SIOP-E brain tumour group, European NF1 society and the Optic Pathway Glioma Working Group in North America were asked to identify case-based criteria for primary observation, treatment or randomisa...
Article
Full-text available
BACKGROUND: Cerebellar mutism syndrome (CMS) is the commonest and most serious complication of posterior fossa tumour surgery with life-long consequences on speech and motor function. Despite previous identification of pre-operative clinical and radiological predictors of CMS, a unifying pre-operative risk stratification model for use during surgic...
Article
Full-text available
BACKGROUND: Public and professional concern about delays in diagnosis of childhood brain tumours has led to a clinical referral guidelines and the HeadSmart campaign to raise awareness of the early features of brain tumours and the need for timely imaging. As part of the outcome evaluation, we have collected data on total diagnostic intervals (TDI)...
Article
INTRODUCTION: Whilst there is an urgent need to expedite the development of new or repurposed drugs for children’s cancer, the additional challenge in the developing brain is to ensure the drug is delivered to the tumour at therapeutic and non toxic concentrations for sufficient duration to achieve the biological effect. This is the necessary focus...
Conference Paper
Full-text available
INTRODUCTION: Vision loss occurs in children with brain tumour due to prolonged pre-diagnostic raised intra-cranial pressure or by direct involvement of visual pathway structures. The HeadSmart campaign was launched in 2011 to disseminate national referral guidelines for brain tumor diagnosis, published in 2008 and demonstrated to be associated wit...
Conference Paper
Ependymoma is the second most common paediatric malignant brain tumour. Overall survival remains relatively poor, and at relapse is dismal. One potential strategy to improve outcome is exploiting the metabolic differences between normal and tumour cells. Under normal physiological conditions, brain cells metabolise glucose for energy. If ‘starved’...
Conference Paper
Aims To describe the presentation of epileptic seizures, the tumour-related risk factors, seizure treatments used and the timing of withdrawal of anti-epileptic drugs (AEDs). Methods Retrospective case note review of 120 newly diagnosed brain tumour patients referred between 01/2010 and 12/2014 to the regional paediatric cancer service was carried...
Article
Objectives: Cisplatin ototoxicity affects 42-88% of treated children. Catechol-O-methyltransferase (COMT), thiopurine methyltransferase (TPMT) and AYCP2 genetic variants have been associated with ototoxicity, but the findings have been contradictory. The aims of the study were as follows: (a) to investigate these associations in a carefully phenot...
Article
Full-text available
Background Childhood brain tumours have some of the longest time to diagnosis. A timely diagnosis may have a role in reducing anxiety in waiting for a diagnosis and subsequent morbidity and mortality. We investigated where the opportunities for an earlier diagnosis were, and for which anatomical locations this strategy will most likely to be effect...
Presentation
Full-text available
Quick recap of our paper on in vitro models of medulloblastoma