CTNI-35. EVALUATE THE SAFETY AND PRELIMINARY EFFICACY OF THE COMBINATION OF NAVIFUS SYSTEM WITH RE-IRRADIATION FOR RGBM PATIENTS

Abstract The blood-brain barrier (BBB) remains the major obstacle in treating patients with malignant brain tumors. Radiation therapy (RT) is the mainstay adjuvant modality regardless of the BBB, but its effectiveness is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown to open the BBB and potentially increase regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). Here, we report an interim analysis of an ongoing single-arm, prospective, pilot study (NCT04988750) combining RT-FUS for recurrent malignant high-grade glioma patients, where re-RT was considered for disease control. FUS-BBB opening was conducted within 2 hours before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression-free survival, overall survival, and adverse events (AEs). In this pilot clinical trial, an interim analysis of six recurrent malignant high-grade glioma patients who underwent a total of 24 RT-FUS treatments was presented. Three patients experienced rapid disease progression after RT-FUS, while the other three patients had at least stable disease after RT-FUS, with or without salvage chemotherapy or targeted therapy. There were no FUS-related AEs, but re-RT-related grade three radiation necrosis was observed. The interim analysis of this ongoing clinical trial showed that the combination of RT-FUS was safe, with no FUS-related adverse effects. Two more cases will be recruited in this trial. A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.