Vidal-Jove, JoanSerres, XavierVlaisavljevich, EliCannata, JonDuryea, AlexMiller, RyanMerino, XavierVelat, ManuelaKam, YossiBolduan, RyanAmaral, JosephHall, TimothyXu, ZhenLee, Fred T., Jr.Ziemlewicz, Timothy J.2022-10-042022-10-042022-12-310265-6736http://hdl.handle.net/10919/112067Rationale Current hepatic locoregional therapies are limited in terms of effectiveness and toxicities. Given promising pre-clinical results, a first in-human trial was designed to assess the technical effectiveness and safety profile of histotripsy, a noninvasive, non-thermal, non-ionizing focused ultrasound therapy that creates precise, predictable tissue destruction, in patients with primary and secondary liver tumors. Methods A multicenter phase I trial (Theresa Study) was performed in a single country with 8 weeks of planned follow-up. Eight of fourteen recruited patients were deemed eligible and enrolled in the study. Hepatic histotripsy, was performed with a prototype system (HistoSonics, Inc., Ann Arbor, MI). Eleven tumors were targeted in the 8 patients who all had unresectable end-stage multifocal liver tumors: colorectal liver metastases (CRLM) in 5 patients (7 tumors), breast cancer metastases in 1 (1 tumor), cholangiocarcinoma metastases in 1 (2 tumors), and hepatocellular carcinoma (HCC) in 1 (1 tumor). The primary endpoint was acute technical success, defined as creating a zone of tissue destruction per planned volume assessed by MRI 1-day post-procedure. Safety (device-related adverse events) through 2 months was a secondary endpoint. Results The 8 patients had a median age of 60.4 years with an average targeted tumor diameter of 1.4cm. The primary endpoint was achieved in all procedures. The secondary safety profile endpoint identified no device-related adverse events. Two patients experienced a continuous decline in tumor markers during the eight weeks following the procedure. Conclusions This first-in-human trial demonstrates that hepatic histotripsy effectively destroys liver tissue in a predictable manner, correlating very well with the planned histotripsy volume, and has a high safety profile without any device-related adverse events. Based on these results, the need for more definitive clinical trials is warranted.application/pdfenCreative Commons Attribution 4.0 InternationalAblationhepatocellular carcinoma (HCC)liver metastasishistotripsyfocused ultrasoundtherapeutic ultrasoundArticle - Refereedhttps://doi.org/10.1080/02656736.2022.2112309391360022431464-5157