Safety and feasibility of focused ultrasound-enabled liquid biopsy in patients with brain tumours
Aperçu du projet
Need for project: Neuropathological diagnoses of brain tumours require invasive neurosurgical biopsies that carry a risk of morbidity or mortality to patients. There has been growing interest in the use of non-invasive liquid biopsies to sample cell-free circulating tumor DNA (ctDNA) for genomic and epigenomic analyses but the abundance of ctDNA in systemic circulation for brain tumour patients is relatively lower than that for systemic cancer patients, limiting sensitivity in this population. Goal of project: We aim to increase the sensitivity of non-invasive biopsy for the brain in a cohort of human subjects by increasing DNA shedding from the tumor into circulation using MRI guided focused ultrasound (MRgFUS). We hypothesize that sensitivity for identifying genomic and epigenomic biomarkers will improve with the increased availability of ctDNA after the application of MRgFUS Project description: MRgFUS causes a significant increase in temperature in a defined focal plane of the multiple (up to 1024) ultrasound beams. We aim to thermally ablate the tumor margin with MRgFUS to disrupt the BBB and allow permeabilization of tumor cell membranes and vessel walls for tumor DNA release into circulation. Plasma samples will be obtained from radiologically diagnosed tumor patients before and after MRgFUS and the accuracy in detecting genomic/epigenomic biomarkers will be compared. Future impact: The overarching goal of this project is to shift the paradigm of brain tumor diagnoses from high-risk invasive procedures to non-invasive diagnostic approaches with potentially additional advantages including the reaching of surgically inaccessible brain regions, capturing tumor al heterogeneity, serial monitoring for tumor progression, and distinguishing tumor from pseudoresponse, presudo progression, or radiation necrosis.
Chef d'équipe
Andres Lozano , University Health Network
Membres de l'équipe
Daniel De Carvalho, Princess Margaret center – UHN
Gelareh Zadeh, University Health Network, Princess Margaret, University of Toronto