Clinical Study on Low-intensity Ultrasound Stimulated Microbubbles to Enhance Neoadjuvant Chemotherapy in Breast Cancer

Abstract

Objective low-intensity ultrasound stimulated microbubbles (USMB), utilizing microbubble-assisted ultrasound cavitation, has the potential to enhance tumor blood perfusion and improve chemotherapy effectiveness. It has been shown to extend survival in pancreatic cancer patients. This study aims to explore the safety and efficacy of USMB in enhancing neoadjuvant chemotherapy(NAC) for breast cancer. Methods Seventeen breast cancer patients were randomly assigned to an experimental group (n = 10) and a control group (n = 7). The experimental group received USMB treatment within 1 hour after each NAC cycle, while the control group underwent ultrasound sham imaging. Adverse events were recorded for both groups. The objective response rate was defined as the percentage of patients who had a best-response rating of complete response (CR) or partial response (PR) confirmed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Tumor perfusion was analyzed through the time-intensity curve (TIC) before and after each USMB treatment, obtaining parameters such as peak enhancement (PE), wash-in area under the curve (WiAUC), wash-out area under the curve (WoAUC), and wash-in and wash-out area under the curve (WiWoAUC). This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2200056718). Results Three out of 17 patients were lost to follow-up. The comparison of adverse event rates between the two groups showed no statistically significant difference. According to the RECIST 1.1, in the experimental group, one subject achieved CR, five subjects achieved PR, and three subjects had stable disease (SD). In the control group, three subjects achieved PR and two subjects had SD. There was no statistically significant difference in the objective response rate (66.7% vs. 60%, p > 0.99). In the experimental group, the PE, WiAUC, WoAUC, and WiWoAUC of breast cancer showed a significant increase compared to pre-USMB treatment (p = 0.03, p = 0.01, p = 0.03, p < 0.01). Conclusions Low-intensity USMB treatment does not increase adverse events to NAC and improves blood perfusion in breast cancer. However, further large-sample, multicenter clinical studies are needed to evaluate the therapeutic efficacy of USMB treatment.