Ko‐Ting Chen, Hong‐Chieh Tsai, Chiung-Yin Huang, Chi‐Ting Liau, Kung‐Chu Ho, Cheng‐Hong Toh, Chi‐Cheng Chuang, Peng‐Wei Hsu, Yin-Cheng Huang, Ting‐Wei Chang, Mun-Chun Yeap, Pin-Yuan Chen, Cheng‐Chi Lee, Ya-Jui Lin, Li-Ying Feng, Raag D. Airan, Gordon Li, Michael Lim, Hao-Li Liu, Kuo‐Chen Wei
BACKGROUND AND OBJECTIVES: Combining focused ultrasound (FUS)-induced blood-brain barrier opening with bevacizumab (BEV) has demonstrated survival benefits in preclinical models. This study aimed to evaluate the safety and feasibility of repeated FUS-BEV treatments in patients with recurrent glioblastoma and to explore imaging and serum biomarkers in relation to disease status. METHODS: This was a prospective, single-arm, open-label pilot trial. The primary end point was 6-month progression-free survival (PFS). Disease progression was assessed according to the Response Assessment in Neuro-Oncology criteria by independent radiological review. Radiological response was evaluated using fluid-attenuated inversion-recovery sequences to compare FUS-exposed vs nonexposed regions. Plasma cell-free DNA (cfDNA) concentrations were measured before and after FUS treatment. RESULTS: Between July 2020 and August 2023, 6 patients received a median of 14.5 sessions of biweekly FUS-BEV (10 mg/kg). The median PFS was 11 months, with a 6-month PFS rate of 66.7%. The only FUS-related adverse event was transient scalp heating (grade 1; 1.9%). A fluid-attenuated inversion recovery normalization effect emerged within 1 month after treatment. Plasma cfDNA increased significantly post-FUS, with total cfDNA rising 2.03 ± 0.76-fold, EGFR cfDNA 1.77 ± 0.76-fold, and HMBS cfDNA 1.68 ± 0.66-fold. CONCLUSION: Repeated FUS-BEV treatment is safe and feasible in patients with recurrent glioblastoma. Randomized controlled trials are warranted to confirm its therapeutic efficacy and validate imaging and liquid biopsy biomarkers.