Safety of Sonazoid in Assisting High-Intensity Focused Ultrasound Ablation Therapy for Advanced Liver Malignant Lesions: A Single-Arm Clinical Study

The aim of the study described here was to evaluate the safety of Sonazoid-assisted high-intensity focused ultrasound (HIFU) in the treatment of advanced malignant liver lesions.A single-arm study was designed to enroll participants who were diagnosed with advanced primary liver cancer or liver metastases and proposed to receive Sonazoid assistance during HIFU treatment. Serological examination was conducted within 1 wk, and side effects in each patient were monitored for 1 mo. To evaluate therapeutic efficacy, the contrast-enhanced magnetic resonance imaging was performed 1 mo after treatment, and short-term follow-up was conducted a year later.A total of 17 participants (12 male, 5 female) with an average age of 58 y (range: 46-73 y) were enrolled, including 11 patients with hepatocellular carcinoma, 2 patients with hepatic metastasis and 4 patients with cholangiocarcinoma. The total volume of tumor mass was 111.82 (11.01-272.30) cm3. The average total ablation time for a patient was 2021 ± 1030 s, and the energy efficiency factor was 5979.7 (3108.0, 45634.5) J/cm3. Immediately after HIFU treatment, 1 patient (5.9%) achieved complete response (CR), 4 patients (23.5%) had a moderate response, 8 patients (47.1%) had partial reperfusion and 4 patients (23.5%) had stable disease (SD). The average ablation rate for all the tumors was 51.5 ± 26.7%. The level of glutamic-pyruvic transaminase (ALT) was mildly increased in 71.6% (12/17) of patients after HIFU therapy. Mean ALT values before and after treatment were 22 (14, 35) U/L and 36 (25, 41) U/L, respectively (Z = 1.947, p = 0.051). Mild or obvious edema in skin and subcutaneous soft tissues were observed in 76.5% of patients, but no serious side effects were found. Twelve months after treatment, the follow-up results revealed that 1 patient (5.8%) achieved a CR, 8 patients (47.1%) had SD and 8 patients (47.1%) had progressive disease. The estimated median time to progression was 11 mo after treatment, with a 95% confidence interval of 6, 11 for all involved patients.Use of Sonazoid is safe and feasible for improving HIFU ablation efficiency during the treatment of advanced malignant liver lesions. The therapeutic efficacy of Sonazoid-assisted HIFU needs to be explored in additional controlled clinical investigations.