OPTIMIZED APPROACHES FOR LIQUID BIOPSY IN GLIOBLASTOMA PATIENTS
type: CreativeWork
description: Background Glioblastoma (GBM) remains the deadliest primary brain tumour, with a 5-year survival < 4 % despite maximal multimodal therapy. Its diffuse infiltration, marked spatial-temporal heterogeneity, and the shielding effect of the blood–brain barrier (BBB) limit the accuracy of tissue biopsy and conventional imaging, hampering truly personalised treatment. To overcome these limitations, novel strategies are needed that can non-invasively capture tumour-specific information Objective This thesis explores three complementary, clinically compatible strategies to enhance the informativity of liquid biopsy: plasma extracellular vesicles (EVs), 5-aminolevulinic-acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence, and focused-ultrasound blood–brain-barrier opening (FUS-BBBO). The objective is to determine whether they can aid in collecting accurate, real-time information on tumour burden and biology, thereby laying the groundwork for precision monitoring and therapy. Methods We enrolled 66 GBM patients, 83 healthy controls and 50 patients with other CNS lesions for the EV arm; 20 tumour patients and 4 healthy volunteers for the 5-ALA arm; and 4 GBM patients across two FUS trials. Plasma-EVs - EVs were isolated by size-exclusion chromatography and quantified/sized with tunable resistive-pulse sensing technology at different timepoints during disease course. PpIX fluorescence - after oral 5-ALA, paired urine, plasma, and serum samples were analyzed with a dedicated fiber-optic spectrometer developed as part of this study and validated against a FluoroMax reader FUS-BBBO - In four GBM patients enrolled in two MR-guided FUS trials, plasma was collected immediately before and 30–60 min after sonication; EV metrics and cfDNA were measured. Results Plasma-EVs distinguish GBM from healthy and non-GBM cohorts with high accuracy (near-perfect AUC), although brain metastases can overlap with GBM. EV concentrations drop sharply 72 h post-resection and rise at recurrence, s…
abstract: Background Glioblastoma (GBM) remains the deadliest primary brain tumour, with a 5-year survival < 4 % despite maximal multimodal therapy. Its diffuse infiltration, marked spatial-temporal heterogeneity, and the shielding effect of the blood–brain barrier (BBB) limit the accuracy of tissue biopsy and conventional imaging, hampering truly personalised treatment. To overcome these limitations, novel strategies are needed that can non-invasively capture tumour-specific information Objective This thesis explores three complementary, clinically compatible strategies to enhance the informativity of liquid biopsy: plasma extracellular vesicles (EVs), 5-aminolevulinic-acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence, and focused-ultrasound blood–brain-barrier opening (FUS-BBBO). The objective is to determine whether they can aid in collecting accurate, real-time information on tumour burden and biology, thereby laying the groundwork for precision monitoring and therapy. Methods We enrolled 66 GBM patients, 83 healthy controls and 50 patients with other CNS lesions for the EV arm; 20 tumour patients and 4 healthy volunteers for the 5-ALA arm; and 4 GBM patients across two FUS trials. Plasma-EVs - EVs were isolated by size-exclusion chromatography and quantified/sized with tunable resistive-pulse sensing technology at different timepoints during disease course. PpIX fluorescence - after oral 5-ALA, paired urine, plasma, and serum samples were analyzed with a dedicated fiber-optic spectrometer developed as part of this study and validated against a FluoroMax reader FUS-BBBO - In four GBM patients enrolled in two MR-guided FUS trials, plasma was collected immediately before and 30–60 min after sonication; EV metrics and cfDNA were measured. Results Plasma-EVs distinguish GBM from healthy and non-GBM cohorts with high accuracy (near-perfect AUC), although brain metastases can overlap with GBM. EV concentrations drop sharply 72 h post-resection and rise at recurrence, s…
author: DEL BENE, MASSIMILIANO
language: eng
keywords: Settore MEDS-15/A - Neurochirurgia
date published: 2025-12-15
date modified: 2026-07-27T20:19:10Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/1193975