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

Margrete Haram; Rune Hansen; David Bouget; Ola Finneng Myhre; Catharina de Lange Davies; Eva Hofsli

doi:10.1016/j.ultrasmedbio.2023.05.013

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

Ultrasound Med Biol. 2023 Sep;49(9):2081-2088. doi: 10.1016/j.ultrasmedbio.2023.05.013. Epub 2023 Jun 17.

Authors

Margrete Haram¹, Rune Hansen², David Bouget², Ola Finneng Myhre³, Catharina de Lange Davies⁴, Eva Hofsli⁵

Affiliations

¹ Department of Radiology and Nuclear Medicine, St. Olav's Hospital-Trondheim University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Cancer Clinic, St. Olav's Hospital-Trondheim University Hospital, Trondheim, Norway. Electronic address: Margrete.Haram@stolav.no.
² Department of Health Research, SINTEF Digital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
³ Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
⁵ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Cancer Clinic, St. Olav's Hospital-Trondheim University Hospital, Trondheim, Norway.

PMID: 37336691
DOI: 10.1016/j.ultrasmedbio.2023.05.013

Abstract

Objective: Pre-clinical trials have obtained promising results that focused ultrasound (FUS) combined with microbubbles (MBs) increases tumor uptake and the therapeutic effect of drugs. The aims of the study described here were to investigate whether FUS and MBs could improve the effect of chemotherapy in patients with liver metastases from colorectal cancer and to investigate the safety and feasibility of using FUS + MBs.

Methods: We included 17 patients with liver metastases from colorectal cancer, selected two lesions in each patient's liver and randomized the lesions for, respectively, treatment with FUS + MBs or control. After chemotherapy (FOLFIRI or FOLFOXIRI), the lesions were treated with FUS (frequency = 1.67 MHz, mechanical index = 0.5, pulse repetition frequency = 0.33 Hz, 33 oscillations, duty cycle = 0.2%-0.4% and MBs (SonoVue) for 35 min). Nine boluses of MBs were injected intravenously at 3.5 min intervals. Patients were scheduled for four cycles of treatment. Changes in the size of metastases were determined from computed tomography images.

Results: Treatment with FUS + MBs is safe at the settings used. There was considerable variation in treatment response between lesions and mixed response between lesions receiving only chemotherapy. There is a tendency toward larger-volume reduction in lesions treated with FUS + MBs compared with control lesions, but a mixed response to chemotherapy and lesion heterogeneity make it difficult to interpret the results.

Conclusion: The combination of FUS and MBs is a safe, feasible and available strategy for improving the effect of chemotherapy in cancer patients. Therapeutic effect was not demonstrated in this trial. Multicenter trials with standardized protocols should be performed.

Keywords: Chemotherapy; Clinical trial; Colorectal cancer; Drug delivery; FOLFIRI; FOLFOXIRI; Liver metastases; Microbubbles; Sonopermeation; Ultrasound.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Blood-Brain Barrier
Colorectal Neoplasms*
Drug Delivery Systems / methods
Humans
Liver Neoplasms* / diagnostic imaging
Liver Neoplasms* / drug therapy
Microbubbles