4.7 Article

Novel MRI-guided focussed ultrasound stimulated microbubble radiation enhancement treatment for breast cancer

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SCIENTIFIC REPORTS
卷 13, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-023-40551-5

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Preclinical studies have shown that focused ultrasound stimulated microbubble rupture can activate the acid sphingomyelinase-ceramide pathway in endothelial cells. When delivered concurrently with radiotherapy, it leads to increased cell death and strong radiosensitization. This is the first human trial of using magnetic resonance imaging guided focused ultrasound microbubble treatment for breast malignancies.
Preclinical studies have demonstrated focused ultrasound (FUS) stimulated microbubble (MB) rupture leads to the activation of acid sphingomyelinase-ceramide pathway in the endothelial cells. When radiotherapy (RT) is delivered concurrently with FUS-MB, apoptotic pathway leads to increased cell death resulting in potent radiosensitization. Here we report the first human trial of using magnetic resonance imaging (MRI) guided FUS-MB treatment in the treatment of breast malignancies. In the phase 1 prospective interventional study, patients with breast cancer were treated with fractionated RT (5 or 10 fractions) to the disease involving breast or chest wall. FUS-MB treatment was delivered before 1st and 5th fractions of RT (within 1 h). Eight patients with 9 tumours were treated. All 7 evaluable patients with at least 3 months follow-up treated for 8 tumours had a complete response in the treated site. The maximum acute toxicity observed was grade 2 dermatitis in 1 site, and grade 1 in 8 treated sites, at one month post RT, which recovered at 3 months. No RT-related late effect or FUS-MB related toxicity was noted. This study demonstrated safety of combined FUS-MB and RT treatment. Promising response rates suggest potential strong radiosensitization effects of the investigational modality.Trial registration: clinicaltrials.gov, identifier NCT04431674.

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