Liver Metastases Clinical Trial: Focused Ultrasound Plus Microbubbles Safely Delivered  


Key Points

  • Researchers and clinicians recently completed a clinical trial in Norway using focused ultrasound plus microbubbles to treat liver metastases. 
  • The study enrolled patients undergoing chemotherapy for colorectal cancer with disseminated metastatic liver disease. 
  • The focused ultrasound plus microbubble treatment was safe and feasible, and the group suggested larger studies with standardized protocols to assess efficacy. 
Medical illustration of a liver

Treatment of Liver Metastases with Focused Ultrasound and Microbubbles in Patients with Colorectal Cancer Receiving Chemotherapy 

Researchers and clinicians from the Norwegian University of Science and Technology and St. Olav’s Hospital-Trondheim University Hospital in Trondheim, Norway, recently completed a clinical trial using focused ultrasound plus microbubbles to treat 17 participants with liver metastases from colorectal cancer. 

With the goals of assessing safety and feasibility to increase tumor uptake of chemotherapy and improve efficacy, the study enrolled 12 males and 5 females with a mean age of 66.5 years from February 2019 to May 2022. The patients were treated with two different chemotherapy regimens, according to national guidelines. Physicians selected two distinctly spaced metastatic lesions easily recognized on CT images and randomized these lesions to control or treatment with focused ultrasound. In each patient, one liver lesion was treated with focused ultrasound plus SonoVue microbubbles (Bracco International) while a control lesion was treated with microbubbles only.  

The enrolled participants first received their intravenous chemotherapy infusion (FOLFIRI or FOLFOXIRI), then underwent the focused ultrasound treatment, which was applied to one lesion for 35 minutes with a GE Vivid E9. The ultrasound scanner incorporated therapeutic ultrasound software and a GE 2-D matrix probe. Nine boluses of the SonoVue microbubbles were injected intravenously every 3.5 minutes during this treatment window. CT imaging was used to measure changes in the size of the selected metastases. 

Although the results showed considerable variation in treatment response, the researchers concluded that the focused ultrasound plus microbubble treatment was safe and feasible. Regarding the variation in treatment response, the authors observed a “tendency toward larger-volume reduction in lesions treated with focused ultrasound plus microbubbles compared with control lesions” but added that “a mixed response to chemotherapy and lesion heterogeneity” made it difficult to interpret these results. 

The group suggested further studies with standardized protocols conducted across multiple centers. 

When we asked Professor Catharina de Lange Davies, PhD, from the Department of Physics at Norwegian University of Science and Technology to comment on the research team’s future directions, she sent the following comments: 

  • “We recently finished a study treating patients with pancreatic cancer with standard chemotherapy (FOLFIRINOX or nab-paclitaxel-gemcitabine) followed by an injection of microbubbles (SonoVue) and ultrasound. For that trial, we developed a novel, dual-frequency ultrasound transducer to enable imaging and localization of the tumor with high frequency ultrasound and treating the tumor using low frequency ultrasound.” 
  • “In collaboration with the Norwegian company EXACT Therapeutics, we studied their Acoustic Cluster Therapy (ACT) technology in mice and reported promising results. ACT creates larger bubbles that are temporarily deposited in capillaries in close contact with the capillary wall and is therefore expected to produce more pronounced effects in the tumor.” 
  • “A similar clinical study as we have reported in liver metastases is currently ongoing with ACT at the Royal Marsden in London. Initial results have been encouraging. At the Norwegian University of Science and Technology and St. Olav’s Hospital, we are now looking forward to taking part in an ACT Phase 2 clinical study. We think that applying microbubbles designed for drug delivery is a promising approach.” 

See Ultrasound in Medicine and Biology (Open Access)