Abstract
IntroductionDespite advances in modern medicine, brain tumor patients are still monitored purely by clinical evaluation and imaging. Traditionally, invasive strategies such as open or stereotactic biopsies have been used to confirm the etiology of clinical and imaging changes. Liquid biopsies can enable physicians to noninvasively analyze the evolution of a tumor and a patient’s response to specific treatments. However, as a consequence of biology and the current limitations in detection methods, no blood or cerebrospinal fluid (CSF) brain tumor-derived biomarkers are used in routine clinical practice. Enhancing the presence of tumor biomarkers in blood and CSF via brain-blood barrier (BBB) disruption with MRI-guided focused ultrasound (MRgFUS) is a very compelling strategy for future management of brain tumor patients.MethodsA literature review on MRgFUS-enabled brain tumor liquid biopsy was performed using Medline/Pubmed databases and clinical trial registries.ResultsThe therapeutic applications of MRgFUS to target brain tumors have been under intense investigation. At high-intensity, MRgFUS can ablate brain tumors and target tissues, which needs to be balanced with the increased risk for damage to surrounding normal structures. At lower-intensity and pulsed-frequency, MRgFUS may be able to disrupt the BBB transiently. Thus, while facilitating intratumoral or parenchymal access to standard or novel therapeutics, BBB disruption with MRgFUS has opened the possibility of enhanced detection of brain tumor-derived biomarkers.ConclusionsIn this review, we describe the concept of MRgFUS-enabled brain tumor liquid biopsy and present the available preclinical evidence, ongoing clinical trials, limitations, and future directions of this application.
Highlights
Despite advances in modern medicine, brain tumor patients are still monitored purely by clinical evaluation and imaging
Liquid biopsy is still constrained by the evolving understanding of tumor biomarkers and their limited representation in body fluids compared to normal tissue elements
The present review describes the current research, applications, challenges, and limitations of combining MRI-guided focused ultrasound (MRgFUS) with brain tumor biomarkers
Summary
From 2013 to 2017, the average annual age-adjusted incidence rate of all central nervous system (CNS) tumors in the United States was 23.79 per 100,000 people [1]. Brain tumor biomarkers can be detected in peripheral blood or CSF (Table 1) [37–67] This way, the evolution of a tumor and a patient’s treatment response could be tracked through a simple, minimally invasive test. CtDNA is detectable in less than 10% of patients with gliomas compared to >75% of patients with other solid tumors, including advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers [44] These limitations point to an urgent clinical need to explore alternative approaches that can noninvasively enhance the release of brain tumorderived biomarkers into the peripheral circulation. The intersection of low-intensity pulsed MRgFUS and liquid biopsies has emerged as a means to improve access to brain tumor biomarkers by inducing transient BBB opening [78–81].
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