Table 1.

Overview of histotripsy applications in-human trials.

Author	Objective	n	Outcome	Follow-up	Adverse effects
Vidal-Jove et al.54	Current hepatic locoregional therapies face efficacy limitations and toxicities, prompting a first in-human trial to assess the technical effectiveness and safety of histotripsy—a noninvasive, focused ultrasound therapy—in patients with primary and secondary liver tumours based on encouraging pre-clinical results.	8	The eight patients, with a median age of 60.4 years and an average targeted tumour diameter of 1.4 cm, all achieved the primary endpoint, and the secondary safety profile analysis revealed no device-related adverse events, with two patients showing a sustained decrease in tumour markers over the eight weeks post-procedure.	8 weeks	No adverse effects reported
Min Wah et al.59	The objective of this phase I/II trial conducted across multiple centres is to evaluate the preliminary safety and effectiveness of the prototype investigational ‘System’ in treating both primary and metastatic liver cancers.	45	Ongoing Trial, no result reported	5 years	NR
Messas et al.56	To evaluate the safety and efficacy of noninvasive ultrasound therapy (NIUT) in calcified aortic stenosis patient	10	The trial, assessed by an independent core laboratory, found no cognitive impairment or significant changes in aortic regurgitation, left ventricular function, or volumes at 1 month; overall, there was a nonsignificant increase in aortic valve area and a decrease in mean pressure gradient, but a subgroup of six responders showed a significant improvement, associated with a longer therapy duration and higher cumulative focal energy delivery, suggesting potential factors linked to treatment response.	1 month	During the procedure, adverse effects included atrial fibrillation, premature ventricular beats, and nonsustained ventricular tachycardia, managed with sedation; chest wall discomfort and arrhythmia were reported, and one patient experienced post-procedure right-sided heart failure, though no deaths or major cardiovascular events occurred at the 1-month follow-up.
Schuster et al.53	The primary objective of the inaugural human study is to evaluate the clinical safety and, as a secondary focus, the efficacy of histotripsy in treating symptomatic benign prostatic enlargement (BPE).	25	Histotripsy treatment in 25 men showed no serious intraoperative adverse events, and although debulking was not observed, there was significant improvement in IPSS scores at one, three, and 6 months postoperatively.	6 months	The adverse effects observed included three cases of transient urinary retention lasting less than three days, one case of serious urinary retention lasting 8 days, a minor anal abrasion, and microscopic haematuria.

IPSS, International Prostate Symptom Score; NR, not reported.