First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study

Rationale 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 u...

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Main Authors: Joan Vidal-Jove, Xavier Serres, Eli Vlaisavljevich, Jon Cannata, Alex Duryea, Ryan Miller, Xavier Merino, Manuela Velat, Yossi Kam, Ryan Bolduan, Joseph Amaral, Timothy Hall, Zhen Xu, Fred T. Lee, Timothy J. Ziemlewicz
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:International Journal of Hyperthermia
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Online Access:https://www.tandfonline.com/doi/10.1080/02656736.2022.2112309
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author Joan Vidal-Jove
Xavier Serres
Eli Vlaisavljevich
Jon Cannata
Alex Duryea
Ryan Miller
Xavier Merino
Manuela Velat
Yossi Kam
Ryan Bolduan
Joseph Amaral
Timothy Hall
Zhen Xu
Fred T. Lee
Timothy J. Ziemlewicz
author_facet Joan Vidal-Jove
Xavier Serres
Eli Vlaisavljevich
Jon Cannata
Alex Duryea
Ryan Miller
Xavier Merino
Manuela Velat
Yossi Kam
Ryan Bolduan
Joseph Amaral
Timothy Hall
Zhen Xu
Fred T. Lee
Timothy J. Ziemlewicz
author_sort Joan Vidal-Jove
collection DOAJ
description Rationale 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 1.4 cm. 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. Trial Registration: Study to Evaluate VORTX Rx (Theresa). NCT03741088. https://clinicaltrials.gov/ct2/show/NCT03741088 KEY POINTSHistotripsy, a new noninvasive, non-thermal, non-ionizing focused ultrasound therapy, safely created a zone of tissue destruction in the liver that correlated very well with the pre-defined planned tissue destruction volume.In this first human trial histotripsy was well tolerated with no histotripsy device-related adverse events and its primary endpoint of acute technical success was achieved in all 8 enrolled patients with primary or secondary liver tumors.This new locoregional therapy for patients with liver tumors is safe and effective, warranting further trials.
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spelling doaj-art-ce91c8ab6b4244dcb1db9a25e36031da2025-08-20T03:51:18ZengTaylor & Francis GroupInternational Journal of Hyperthermia0265-67361464-51572022-12-013911115112310.1080/02656736.2022.2112309First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility studyJoan Vidal-Jove0Xavier Serres1Eli Vlaisavljevich2Jon Cannata3Alex Duryea4Ryan Miller5Xavier Merino6Manuela Velat7Yossi Kam8Ryan Bolduan9Joseph Amaral10Timothy Hall11Zhen Xu12Fred T. Lee13Timothy J. Ziemlewicz14Institute Khuab for Interventional Oncology, Comprehensive Tumor Center, Barcelona, SpainDepartment of Interventional Ultrasound, Vall d’Hebron University Hospital, Barcelona, SpainDepartment of Biomedical Engineering, Virginia Polytechnic University, Blacksburg, VirginiaResearch and Development, Histosonics, Inc, Ann Arbor, MI, USAResearch and Development, Histosonics, Inc, Ann Arbor, MI, USAResearch and Development, Histosonics, Inc, Ann Arbor, MI, USADepartment of Interventional Ultrasound, Vall d’Hebron University Hospital, Barcelona, SpainInstitute Khuab for Interventional Oncology, Comprehensive Tumor Center, Barcelona, SpainR&D Clinical Excellence, Philips Healthcare, Haifa, IsraelClinical Research and Medical Affairs, Histosonics, Inc, Ann Arbor, MI, USAClinical Research and Medical Affairs, Histosonics, Inc, Ann Arbor, MI, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USADepartment of Radiology, University of Wisconsin, Madison, WI, USADepartment of Radiology, University of Wisconsin, Madison, WI, USARationale 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 1.4 cm. 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. Trial Registration: Study to Evaluate VORTX Rx (Theresa). NCT03741088. https://clinicaltrials.gov/ct2/show/NCT03741088 KEY POINTSHistotripsy, a new noninvasive, non-thermal, non-ionizing focused ultrasound therapy, safely created a zone of tissue destruction in the liver that correlated very well with the pre-defined planned tissue destruction volume.In this first human trial histotripsy was well tolerated with no histotripsy device-related adverse events and its primary endpoint of acute technical success was achieved in all 8 enrolled patients with primary or secondary liver tumors.This new locoregional therapy for patients with liver tumors is safe and effective, warranting further trials.https://www.tandfonline.com/doi/10.1080/02656736.2022.2112309Ablationhepatocellular carcinoma (HCC)liver metastasishistotripsyfocused ultrasoundtherapeutic ultrasound
spellingShingle Joan Vidal-Jove
Xavier Serres
Eli Vlaisavljevich
Jon Cannata
Alex Duryea
Ryan Miller
Xavier Merino
Manuela Velat
Yossi Kam
Ryan Bolduan
Joseph Amaral
Timothy Hall
Zhen Xu
Fred T. Lee
Timothy J. Ziemlewicz
First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study
International Journal of Hyperthermia
Ablation
hepatocellular carcinoma (HCC)
liver metastasis
histotripsy
focused ultrasound
therapeutic ultrasound
title First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study
title_full First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study
title_fullStr First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study
title_full_unstemmed First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study
title_short First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study
title_sort first in man histotripsy of hepatic tumors the theresa trial a feasibility study
topic Ablation
hepatocellular carcinoma (HCC)
liver metastasis
histotripsy
focused ultrasound
therapeutic ultrasound
url https://www.tandfonline.com/doi/10.1080/02656736.2022.2112309
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