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

• Published in: Scientific reports Vol. 13; no. 1; pp. 13566 - 11
• Main Authors: Dasgupta, Archya, Saifuddin, Murtuza, McNabb, Evan, Ho, Ling, Lu, Lin, Vesprini, Danny, Karam, Irene, Soliman, Hany, Chow, Edward, Gandhi, Sonal, Trudeau, Maureen, Tran, William, Curpen, Belinda, Stanisz, Greg, Sahgal, Arjun, Kolios, Michael, Czarnota, Gregory J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.08.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67; 631/67/1347; 692/4028/67/1059; Acute toxicity; Apoptosis; Breast cancer; Cell death; Dermatitis; Endothelial cells; Humanities and Social Sciences; Magnetic resonance imaging; Malignancy; multidisciplinary; Radiation therapy; Radiosensitization; Science; Science (multidisciplinary); Sphingomyelin phosphodiesterase; Toxicity; Tumors; Ultrasonic imaging; Ultrasound
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-40551-5

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.