BIOM-05 - First-in-human prospective trial of sonobiopsy in glioblastoma patients using neuronavigation-guided focused ultrasound

Friday, November 17, 2023

11:55 AM – 12:00 PM PT

Location: Room 118-120

Oral Abstract Presenter(s)

Jinyun Yuan

Washington University in St Louis
St Louis, Missouri, United States

Author(s)

LX

Lu Xu

Washington University in St Louis
St Louis, United States
CC

Chih-Yen Chien

Washington University in St Louis
St Louis, United States
YY

Yaoheng Yang

Washington University in St Louis
St Louis, Missouri, United States
YY

Yimei Yue

Washington University in St Louis
St Louis, United States
SF

Siaka Fadera

Washington University in St Louis
St Louis, United States
AS

Andrew H. Stark

Washington University in St Louis
St Louis, United States
KS

Katherine Schwetye

Washington University in St. Louis
St Louis, United States
AN

Arash Nazeri

Washington University in St. Louis
St Louis, United States
RD

Rupen Desai

Washington University in St. Louis
St Louis, Missouri, United States
UA

Umeshkumar Athiraman

Washington University in St. Louis
St Louis, United States
AC

Aadel Chaudhuri

Washington University in St. Louis
St Louis, United States
HC

Hong Chen

Washington University in St Louis
St Louis, United States
EL

Eric C. Leuthardt

Washington University School of Medicine
St. Louis, Missouri, United States

Introduction Blood-based liquid biopsy for brain cancer offers a noninvasive alternative to invasive surgical biopsies. However, the presence of the blood-brain barrier (BBB) limits the release of brain tumor-derived molecular biomarkers into the bloodstream for sensitive diagnosis. Focused ultrasound (FUS)-enabled blood-based liquid biopsy (sonobiopsy) locally disrupts the BBB and releases tumor-derived biomarkers into blood circulation. Our previous studies have demonstrated that sonobiopsy improved the detection sensitivity of glioblastoma (GBM)-specific cirulating tumor DNA (ctDNA) in animal models of GBM. This study aimed to evaluate the feasibility and safety of sonobiopsy in enriching circulating tumor biomarkers in a first-in-human, prospective clinical trial. Methods Five GBM patients (G01-05) were enrolled in the initial study. The sonobiopy procedures were performed prior to tumor resection, using a nimble FUS device integrated with a clinical neuronavigation system. The plasma level of glial fibrillary acidic protein (GFAP) was quantified using ultrasensitive single-molecule array (Simoa), while the cell-free DNA (cfDNA) levels were quantified using Bioanalyzer. Patient-specific tumor variants were comprehensively analyzed using a personalized tumor-informed ctDNA assay (Invitae Personalized Cancer Monitoring assay). Additionally, the two most common GBM-specific tumor variants were analyzed using customized ddPCR assays. Results Analysis of plasmas collected before and after FUS sonication showed sonobiopsy enhanced plasma circulating tumor biomarker levels, including a maximum increase of 1.3-fold for GFAP, 1.6-fold for the concentration of mono-nucleosomal cfDNA fragment (120–280 bp), 1.9-fold increase in patient-specific tumor variant levels, and 5.6-fold increase in the TERT mutation level. Histological analysis of surgically resected tumors confirmed the safety of the procedure. Transcriptome analysis of sonicated and nonsonicated tumor tissues found that FUS sonication mainly modulated cell physical structure-related genes. ConclusionsThese feasibility and safety data support the continued investigation of sonobiopsy for noninvasive molecular diagnosis of brain diseases.