Publications by authors named "Colin Watts"

Background: Tumor resistance represents a major challenge in the current oncology landscape. Asparagine endopeptidase (AEP) overexpression correlates with worse prognosis and reduced overall survival in most human solid tumors. However, the underlying mechanisms of the connection between AEP and reduced overall survival in cancer patients remain unclear.

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  • Patients with brain tumors want to help doctors understand their illness better by participating in tests that involve taking samples of their tumor tissue.
  • To improve treatments, everyone including patients, researchers, and regulatory agencies need to work together and use consistent methods when taking these samples.
  • Even though new tests using blood samples show some promise, they can't replace the need for the usual tissue tests just yet, and it's important to clearly explain the risks and benefits of these procedures to patients.
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  • The study focuses on the T2-FLAIR mismatch sign, which indicates a specific type of astrocytoma with IDH mutations, and how this sign changes as the tumor progresses.
  • A total of 128 IDH-mutant gliomas were analyzed using advanced MRI techniques to observe the evolution of the T2-FLAIR mismatch and the tumors' internal variations over time.
  • The research shows that smaller tumors start as uniform T2 lesions but develop a T2-FLAIR mismatch as they grow, while larger tumors demonstrate increased heterogeneity, suggesting a progression to higher grade tumors.
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  • A systematic review was conducted to analyze how outcomes of meningioma clinical trials are measured and reported, addressing the lack of agreement on these measures.
  • The study reviewed 30 published articles and 18 ongoing trials, resulting in 47 clinical trials and 659 reported outcomes, which were grouped into unique terms using a standardized classification system.
  • The findings highlight the need for a more consistent approach to outcome measurement, leading to plans for a consensus meeting to create a core outcome set to guide future trials.
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  • A systematic review was conducted to analyze how outcomes are measured in studies of patients with incidental intracranial meningioma, as inconsistent practices have hindered comparative research.
  • The review included 33 published articles, resulting in 268 reported outcomes, which were refined to 178 unique outcomes categorized into 53 standardized terms and classified into 9 outcome domains.
  • The goal is to create a Core Outcome Set through stakeholder consensus, improving the consistency of outcome measurements in future studies.
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The treatment for Glioblastoma is limited due to the presence of the blood brain barrier, which restricts the entry of chemotherapeutic drugs into the brain. Local delivery into the tumor resection margin has the potential to improve efficacy of chemotherapy. We developed a safe and clinically translatable irinotecan implant for local delivery to increase its efficacy while minimizing systemic side effects.

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Background: Brain metastases account for more than 50% of all intracranial tumors and are associated with poor outcomes. Treatment decisions in this highly heterogenous cohort remain controversial due to the myriad of treatment options available, and there is no clearly defined standard of care. The prognosis in brain metastasis patients varies widely with tumor type, extracranial disease burden and patient performance status.

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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.

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European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCCs) are explanations of the organisation and actions necessary to provide high-quality care to patients with a specific cancer type. They are compiled by a working group of European experts representing disciplines involved in cancer care, and provide oncology teams, patients, policymakers and managers with an overview of the essential requirements in any healthcare system. The focus here is on adult glioma.

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Background: IDH-wildtype glioblastoma (GBM) is a highly malignant primary brain tumor with a median survival of 15 months after standard of care, which highlights the need for improved therapy. Personalized combination therapy has shown to be successful in many other tumor types and could be beneficial for GBM patients.

Methods: We performed the largest drug combination screen to date in GBM, using a high-throughput effort where we selected 90 drug combinations for their activity onto 25 patient-derived GBM cultures.

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Background: Improving intraoperative accuracy with a validated surgical biomarker is important because identifying high-grade areas within a glioma will aid neurosurgical decision-making and sampling.

Methods: We designed a multicentre, prospective surgical cohort study (GALA-BIDD) to validate the presence of visible fluorescence as a pragmatic intraoperative surgical biomarker of suspected high-grade disease within a tumour mass in patients undergoing 5-aminolevulinic acid (5-ALA) fluorescence-guided cytoreductive surgery.

Results: A total of 106 patients with a suspected high-grade glioma or malignant transformation of a low-grade glioma were enrolled.

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  • Researchers studied glioblastoma, a type of brain cancer, to improve treatments by looking at how these tumors change over time.
  • They used special tests (RNA sequencing) on tumor samples from patients to see how the cells and their environment evolve when the tumors come back after treatment.
  • The study found that instead of changing the main cancer genes, the tumors' surroundings changed a lot, which affected how patients did after their tumors came back.
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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.

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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.

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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.

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Zika virus (ZIKV) can infect human developing brain (HDB) progenitors resulting in epidemic microcephaly, whereas analogous cellular tropism offers treatment potential for the adult brain cancer, glioblastoma (GBM). We compared productive ZIKV infection in HDB and GBM primary tissue explants that both contain SOX2+ neural progenitors. Strikingly, although the HDB proved uniformly vulnerable to ZIKV infection, GBM was more refractory, and this correlated with an innate immune expression signature.

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Background: Glioblastoma (GB) is the most common intrinsic brain cancer and is notorious for its aggressive nature. Despite widespread research and optimization of clinical management, the improvement in overall survival has been limited. The aim of this study was to characterize the impact of service reconfiguration on GB outcomes in a single centre.

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  • Late-phase platform protocols, such as basket and master protocols, are more efficient than traditional two-arm trials but are underutilized; this study shares operational recommendations from successful implementations.* -
  • A meeting of UK clinical trial experts was held to discuss the practical challenges and operational aspects specific to running late-phase platform trials, leading to a set of guidance for trialists.* -
  • The recommendations cover all stages of a platform trial, emphasizing key areas like protocol development, funding, staffing, data management, and effective communication with participants and stakeholders.*
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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).

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  • This study aimed to assess glioblastoma metabolism using hyperpolarized carbon-13 MRI by tracking the exchange of hyperpolarized carbon from injected [1-C]pyruvate to tumor lactate and bicarbonate.
  • Seven treatment-naive GBM patients underwent imaging, revealing that the bicarbonate-to-pyruvate ratio was significantly lower in tumors compared to normal brain areas, while lactate levels were similar.
  • The research indicated strong correlations between the intensities of lactate and bicarbonate signals and pyruvate, suggesting variations in tumor metabolism that could have implications for understanding glioblastoma.
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The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions.

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  • The Neurology and Neurosurgery Interest Group holds an annual Careers Day to help people learn about neurosurgery and encourage applications to its training program.
  • At the ninth event, 77 attendees were surveyed before and after to understand their experiences and what attracted or discouraged them from neurosurgery.
  • The event improved knowledge about neurosurgery careers and sparked more interest, but many still found the competition tough and the hours long, although nearly all would recommend attending.
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  • Meningiomas are the most common type of primary brain tumor in adults, mostly non-cancerous, but some can be aggressive, requiring different management strategies depending on symptoms and growth.
  • Two specialized sets of outcomes (COS: Intervention and COS: Observation) will be created to standardize how results are measured in clinical trials and studies of incidental meningiomas.
  • The study will utilize systematic literature reviews and focus group surveys to identify, categorize, and prioritize outcomes, with ethical approval and consent processes in place for participant involvement.
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  • Core Outcome Sets (COS) establish essential metrics for measuring and reporting on clinical trials within a specific health context, but none exist yet for neuro-oncology, which is crucial for effective research design.
  • COS development must focus on scope, stakeholder engagement (including patients), consensus methods (like Delphi surveys), and dissemination plans.
  • Challenges in neuro-oncology include diverse tumor classifications, varying symptoms based on tumor location, and differing treatment options, making it difficult to create a COS that is neither too narrow nor too broad, as highlighted in ongoing projects for specific conditions like adult glioma and pediatric brain tumor surgical interventions.
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