A prospective randomized controlled trial to determine the safety and efficacy of extracorporeal shock waves therapy for primary prevention of subclinical cardiotoxicity in breast cancer patients without a cardiovascular risk treated with doxorubicin

Abstract

Background: Doxorubicin is a highly effective anti-cancer drug that causes left ventricular (LV) dysfunction and induces late-onset cardiomyopathy. However, an effective and clinically applicable preventive treatment is yet to be discovered.

Objective: Cardiac-Extracorporeal shockwave therapy (C-ESWT) has been suggested to treat inflammatory and ischemic diseases and protect cardiomyocytes from doxorubicin-induced cardiomyopathy. This study aims to assess the safety and efficacy of C-ESWT in the prevention of subclinical cardiotoxicity.

Methods: We enrolled 64 breast cancer patients. C-ESWT group 33 patients were treated with our C-ESWT (200 shots/spot at 0.09 mJ/mm² for 20 spots, 3 times every six weeks). The efficacy endpoints were the difference in left ventricular global longitudinal strain (LVGLS) change by 2D speckle tracking echocardiography and chemotherapy-related cardiac dysfunction (CTRCD). Echocardiography was performed on the baseline line and every 4 cycles of chemotherapy, followed by a follow-up 3,6 months after chemotherapy to compare the incidence of cardiomyopathy of subclinical LV dysfunction due to chemotherapy between the two groups.

Results: Participants averaged 50 ± 9 years in age, 100% female. In the results of follow-up 6 months after the end of chemotherapy, there was a significant difference in delta LVGLS between the C-ESWT group and the control group (LVGLS; -1.1 ± 10.9% vs. -11.5 ± 11.6% p-value; <0.001). A total of 23% (15 patients) of patients developed CTRCD (Control group; 13 vs. C-ESWT group; (2). C-ESWT was performed safely without any serious adverse events.

Conclusion: In this prospective study, C-ESWT established efficacy in preventing subclinical cardiotoxicity, especially in breast cancer patients using doxorubicin chemotherapy, and the safety of C-ESWT.

Clinical trial registration: ClinicalTrials.gov, identifier (NCT05584163).

Keywords: breast cancer; cancer therapy-related cardiac dysfunction; cardiac extracorporeal shock wave therapy; doxorubicin; left ventricular global longitudinal strain/LV GLS.