Human clinical trial using diagnostic ultrasound and microbubbles to enhance neoadjuvant chemotherapy in HER2- negative breast cancer

Abstract

BackgroundIn vivo and in vitro experiments have demonstrated that diagnostic ultrasound combined with microbubbles (USMB) can enhance tumor chemotherapy, but few clinical studies have explored the effect of USMB in human HER2-negative breast cancer. We aimed to compare USMB combined with neoadjuvant chemotherapy (NAC) with NAC alone in the treatment of human HER2-negative breast cancer.MethodsPatients (n=10) enrolled in the study were treated with TAC (taxane – (docetaxel), anthracycline – (epirubicin or doxorubicin liposomes), and cyclophosphamide) and ultrasound using a commercial clinical ultrasound scanner for 20 min after each chemotherapy session, followed by intermittent injections of SonoVue® to induce sonoporation and enhance therapeutic efficacy. Contrast-enhanced ultrasound (CEUS) was used to record tumor perfusion before and after ultrasound treatment.ResultsAfter completion of chemotherapy, the maximum tumor diameter of patients in the combined treatment group (n=10) was significantly smaller than that in the control group (n=16) (p=0.017). Although the combined treatment group had higher overall response and clinical benefit rates than those in the control group, there was no statistically significant difference in RECIST between the combined treatment group and the control groups (p=0.590). More patients in the combination therapy group achieved pathologic complete response than in the control group (p=0.014). For combined treatment, CEUS revealed that the peak intensity, mean transit time, and area under the curve were higher after treatment than before treatment (p<0.001, p<0.001, p=0.003, respectively). Combined therapy did not cause additional toxicity or increase side effects.ConclusionUSMB and chemotherapy can be combined in a clinical setting using commercially available equipment, without additional toxicity, and may improve the efficacy of NAC in HER2-negative breast cancer.

EFSUMB Technical Review – Update 2023: Dynamic Contrast-Enhanced Ultrasound (DCE-CEUS) for the Quantification of Tumor Perfusion

“…Early clinical trials assessing tumor response in gastrointestinal stromal tumor (GIST) were based on the subjective and qualitative assessment of enhancement dynamics. Subsequent studies assessed response in renal cell carcinoma, hepatocellular carcinoma (HCC), breast cancer, pancreatic cancer, and colorectal metastases using semi-quantitative techniques [55,56,57,58,59,60,61,62,63,64,65]. Additional studies [50,51,56] used quantitative techniques to derive parameters related to the time course of contrast enhancement, in comparison to clinical endpoints such as Progression Free Survival (PFS) and Overall Survival (OS) following anti-angiogenic treatment.…”

Sonosensitive Cavitation Nuclei—A Customisable Platform Technology for Enhanced Therapeutic Delivery

“…Several pre-clinical studies have used co-administered cavitation nuclei to significantly enhance the delivery of co-administrated small molecules [111][112][113][114], antibodies, viral vectors [115][116][117][118], and nucleic acids [119][120][121]. There have also been several clinical trials evidencing the successful use of gas-filled microbubbles particles (such as Sonovue ® , Optison ® , Definity ® ) which have been approved as diagnostic ultrasound contrast agents to enhance the effects of standard chemotherapy in the context of chemotherapy for pancreatic cancer [122,123] or to treat pathologies that lie beyond the blood-brain barrier [124,125]. Most recently, a new class of solid gas-stabilizing CN (OxSonics SonoTran particles) were cleared by the UK's Medicines and Health Regulatory Authority (MHRA) to enter first-inhuman clinical trials (NCT02181075) for the enhancement of the delivery of co-administered small-molecule chemotherapeutics and antibodies to treat metastatic colorectal cancer in the liver.…”