This prospective study aims to characterize blood brain barrier (BBB) disruption in patients with newly diagnosed glioblastoma multiforme undergoing surgical resection. The study integrates advanced MRI, circulating BBB biomarkers, neurocognitive assessment, and molecular analysis of tumor tissue to investigate relationships between BBB integrity, tumor biology, and neurological function. Participants will undergo serial assessments before surgery, after surgery, and following radiotherapy. Tumor tissue collected during standard-of-care resection will undergo immunohistochemical and transcriptional
Glioblastoma is characterized by disruption of the blood-brain barrier, which may influence tumor progression, neurological dysfunction, treatment delivery, and clinical outcomes. This study seeks to comprehensively characterize BBB integrity using multimodal approaches. Participants with newly diagnosed GBM selected for surgical resection will undergo: * Clinical and demographic data collection. * Neurocognitive assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Reading the Mind in the Eyes Test (RMET). * High-resolution 3-Tesla MRI with and without gadolinium contrast, including structural and functional imaging sequences. * Blood sampling for measurement of biomarkers associated with BBB disruption and neuronal injury, including S100β, GFAP, UCHL1, amyloid beta, phosphorylated tau, and neuron-specific enolase. * Collection of tumor tissue during routine surgical resection for immunohistochemical and transcriptional analyses. Serial evaluations will be performed preoperatively, postoperatively, at 72 hours, at 4 weeks, and 4 weeks following completion of radiotherapy, according to the assessment schedule.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
100
A standardised multimodal diagnostic assessment designed to characterize blood brain barrier integrity in patients with newly diagnosed glioblastoma. The intervention includes advanced contrast enhanced MRI, serial blood sampling for measurement of blood-brain barrier and neuronal injury biomarkers (including S100β, GFAP, UCHL1, amyloid beta, phosphorylated tau, and neuron-specific enolase), neurocognitive assessments, and immunohistochemical and transcriptional analyses of tumor tissue obtained during standard-of-care surgical resection. Assessments are performed longitudinally before surgery, after surgery, at 72 hours, at 4 weeks, and following completion of radiotherapy.
Beaumont RCSI Cancer Centre
Beaumont, Ireland
RECRUITINGSerum Biomarkers of Blood-Brain Barrier Disruption and Neuronal Injury
Serial measurement of serum biomarkers associated with blood-brain barrier disruption and neuronal injury, including S100β, GFAP, UCHL1, amyloid beta, phosphorylated tau, and neuron-specific enolase. Biomarker concentrations will be assessed longitudinally to characterize changes in blood-brain barrier integrity in patients with newly diagnosed glioblastoma undergoing surgical resection and radiotherapy.
Time frame: Baseline (within 7 days before surgery), intraoperative, within 24 hours after surgery, 72 hours after surgery, 4 weeks after surgery, and 4 weeks after completion of radiotherapy
MRI Based Measures of Blood-Brain Barrier Integrity
Assessment of blood-brain barrier disruption using contrast-enhanced 3-Tesla MRI, including quantitative and qualitative radiological measures of tumour enhancement and permeability. Imaging findings will be evaluated longitudinally and correlated with circulating biomarkers and clinical outcomes.
Time frame: 4 weeks after surgery
Immunohistochemical Characterisation of Blood-Brain Barrier Disruption
Expression of blood-brain barrier-associated proteins within resected glioblastoma tissue assessed by immunohistochemical analysis. Findings will be used to characterize blood-brain barrier integrity and correlated with circulating biomarker and imaging measures.
Time frame: During surgical resection (single assessment)
Transcriptional Characterisation of Blood-Brain Barrier Disruption
Gene expression profiling of resected glioblastoma tissue to identify transcriptional signatures associated with blood-brain barrier disruption and tumour biology. Results will be correlated with blood biomarker and imaging findings.
Time frame: During surgical resection (single assessment)
Neurocognitive Function Assessed by RBANS
Neurocognitive performance measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Changes in cognitive function will be examined in relation to blood-brain barrier integrity and treatment.
Time frame: Baseline (within 7 days before surgery), 4 weeks after surgery, and 4 weeks after completion of radiotherapy
Professor Donncha O'Brien, MB, BCh, BAO, MCh, FRCSI (SN)
CONTACT
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