Update artikel 11 juni 2025:

lees ook het verhaal van Chris Donaldson die in 2024 werd behandeld met  histotripsy voor zijn leveruitzaaiingen afkomstig vanuit zijn oogmelanoom, met uitleg via video hoe  histotripsy wordt toegepast 

New treatment called histotripsy kills cancer cells with sound and water

In het Providence Mission Hospital kun je via een formulier vragen of je in aanmerking kan komen voor een behandeling met histotripsy. 

Zie verder ook hieronder meer over histotripsy, over lopende en afgesloten studies enz. 

Update 26 mei 2025:

Naar aanleiding van mijn bezoek aan Weber Medical samen met mevrouw R. (uitgezaaide zwaar voorbehandelde borstkanker) ben ik nog eens op zoek gegaan of er nieuwe ontwikkelingen zijn met histotripsy. Op een website van de producent van de histotripsy, een machine die via Ultra Sound kwaadaardige en goedaardige tumoren kan vernietigen zonder gezond tumorweefsel te beschadigen, staan een aantal abstracten van dierstudies, patiëntenstudies en lopende studies in zowel Amerika als in Europa. 

Een klein stukje vertaald in het Nederlands uit het Engels, referentienummers staan onderaan in referentielijst:

Onze groep heeft histotripsie bestudeerd voor de behandeling van leverkanker[1,2], prostaatkancer [3-5], nierkanker [6,7], melanomen [8], alvleesklierkanker en immuunstimulatie [8,9]. Ons onderzoek heeft geleid tot een fase I-studie naar de behandeling van goedaardige prostaathyperplasie (NCT01896973), een fase I studie naar de behandeling van leverkanker (NCT03741088) [11,12], en klinische studies in meedere ziekenhuizen naar de behandeling van leverkanker in de VS (NCT04572633) en Europa (NCT04573881), allemaal met behulp van HistoSonics-apparaten.

Onderaan dit artikel staat een referentielijst behorend bij bovenstaande informatie.

Een andere interessante studie is deze, abstract staat v erderop in dit artikel: 

Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers



En lees vooral ook verder in dit artikel.......

23 juli 2024: met dank aan Pascale die me dit doorstuurde.

Emma van Dijk, Arts-onderzoeker, internist-oncoloog i.o. laat aan Pascale weten dat de iFocus studie goedkeuring heeft gekregen om patiënten te werven voor een studie waarin histotripsy gecombineerd gaat worden met immuuntherapie met checkpointremmers nivolumab en ipilimumab. 

Wie is geïnteresseert lees eerst deze PDF die de studie beschrijft met inclusie- en exclusiecriteria, dus welke kankerpatiënten er wel en niet voor in aanmerking komen.

De fase I studie begint met 6 deelnemers en uiteindelijk zullen aan deze studie 24 personen kunnen deelnemen. 

Een belangrijke zin uit de studieopzet:  "Histotripsie heeft dus de potentie om een 'koude' niet-immunogene tumor om te zetten in een 'hete' immuunresponsieve tumor"

Zie verder in dit artikel meer informatie over histotripsie. 

12 april 2024: Voor wie is geinteresseerd in Ultra Sound behandeling van levertumoren lees dit artikel. Met onderaan in artikel contactadres van arts Matteo Fusaglia die in het Antoni van Leeuwenhoek ziekenhuis voor het NKI de studie met Ultra Sound bij Intra-operatieve navigatie gaat uitvoeren voor zijn promotieonderzoek.

30 november 2023:

Zie ook dit artikel: https://kanker-actueel.nl/histotripsy-een-vorm-van-ultra-sound-met-gepulseerde-geluidsgolven-gericht-op-gasbellen-in-tumorweefsel-is-ook-succesvol-bij-osteosarcomen-in-dierstudies.html

28 november 2023: Zie ook in gerelateerde artikelen

27 november 2023: Bron: Histosonics, 2022;39(1):1115-1123 Met dank aan Jacques die mij deze specifieke Ultra sound behandeling toestuurde.

Ultra Sound is een al tientallen jaren gebruikte techniek om tumorweefsel te vernietigen. Jacques wees me op een hele speciale vorm van Ultra Sound die Histotripsy genoemd.

Histotripsy maakt gebruik van gepulseerde geluidsgolven om “bellenwolken” te veroorzaken uit gassen die van nature aanwezig zijn in het beoogde tumorweefsel. Deze bellenwolken vormen en storten in microseconden in wanneer een arts / PDT specialist het Edison apparaat op de tumoren richt, waardoor mechanische krachten ontstaan die sterk genoeg zijn om weefsel op cellulair en subcellulair niveau te vernietigen op een niet-invasieve en niet-thermische methode.

Histotripsy maakt gebruik van de kracht van microbellen gas om gericht kwaadaardige weefsels te vernietigen en vermijdt ioniserende energie van straling, hitteschade door thermische modaliteiten en gebruikt geen operatie of zelfs geen naalden die traditionele behandelingen wel gebruiken.

Voordelen van de Histotripsy behandeling zijn: 

  • Het is een veilige en niet invasieve manier van behandelen
  • Er is geen operatie of injectie nodig. Alles gaat vanaf de buitenkant en de geluidsgolven (Ultra Sound) doen het werk
  • De behandeling kan vele malen herhaald worden
  • Er wordt geen normaal celweefsel geraakt en een behandeling geeft daardoor amper bijwerkingen

Nadelen: 

  • Per behandeling kunnen alleen kleine tumoren in zacht weefsel worden behandeld. Botuitzaaiingen kunnen overigens ook worden behandeld maar zijn alleen nog in dierstudies onderzocht.
  • Alleen voor levertumoren is toestemming terwijl deze behandelingen ook voor meerdere vormen van kanker geschikt is
  • Alleen een in PDT en Ultra Sound geschoolde arts mag het uitvoeren

Uit een studieverslag:

Hier twee foto's van levertumor, bovenste foto is van voor de behandelingen en daaronder twee maanden later:

An arrow pointing at a white spot in a scan


An arrow pointing at a dark spot in a scan


De Amerikaanse FDA keurde al in 2018 de Histotripsy goed om levertumoren niet-invasief te behandelen  Gepubliceerd: 9 oktober 2023: https://www.fusfoundation.org/posts/histosonics-focused-ultrasound-platform-receives-fda-breakthrough-device-designation/

HistoSonics – genaamd EdisonTM – goedgekeurd voor de behandeling van levertumoren. Dit is de negende klinische indicatie waarvoor gerichte ultrasone behandeling is goedgekeurd door de FDA.*

EdisonTM maakt gebruik van histotripsy om op niet-invasieve wijze weefsel in de lever te vernietigen en is het eerste en enige platform dat beschikbaar is in de VS en inmiddels ook in Europa. Dit is ook de eerste keer dat het gebruik van histotripsy wereldwijd goedkeuring van de regelgevende instanties heeft gekregen.

De FDA-goedkeuring werd verleend op basis van gegevens uit de klinische onderzoeken #HOPE4LIVER van HistoSonics, waarin deze methode werd getest bij 44 patiënten met primaire en gemetastaseerde levertumoren op 14 locaties in de VS en Europa.

Op deze pagina staan enkele video's over ontstaan van de Histotripsy en verwijzingen naar studies.

Op deze pagina staat het studieprotocol van een lopende studie met referentielijst. In deze studie worden ook loacaties in Europa genoemd waar patienten een behandeling met Histotripsy kunnen krijgen. Artsen kunnen scholing krijgen om met de Histosonic te werken met patiënten: https://histosonics.com/education/

De laatste publicatie is van oktober 2023. Hieronder het abstract met referentielijst maar volledige studierapport is gratis in te zien of te downloaden:

Multicenter Study
 
. 2022;39(1):1115-1123.
 doi: 10.1080/02656736.2022.2112309.

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

Joan Vidal-Jove 1, Xavier Serres 2, Eli Vlaisavljevich 3, Jon Cannata 4, Alex Duryea 4, Ryan Miller 4, Xavier Merino 2, Manuela Velat 1, Yossi Kam 5, Ryan Bolduan 6, Joseph Amaral 6, Timothy Hall 7, Zhen Xu 7, Fred T Lee Jr 8, Timothy J Ziemlewicz 8
Affiliations 
Free article

Abstract

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.

Keywords: Ablation; focused ultrasound; hepatocellular carcinoma (HCC); histotripsy; liver metastasis; therapeutic ultrasound.

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Referenties:

[1]  Worlikar, T., Zhang, M., Ganguly, A., Hall, T. L., Shi, J., Zhao, L., Lee, F. T., Mendiratta- Lala, M., Cho, C. S. & Xu, Z. Impact of Histotripsy on Development of Intrahepatic Metastases in a Rodent Liver Tumor Model. Cancers (Basel) 14, 1612, (2022). PMC8996987

[2]  Worlikar, T., Mendiratta-Lala, M., Vlaisavljevich, E., Hubbard, R., Shi, J., Hall, T. L., Cho, C. S., Lee, F. T., Greve, J. & Xu, Z. Effects of Histotripsy on Local Tumor Progression in an in vivo Orthotopic Rodent Liver Tumor Model. BME Frontiers, (2020).

[3]  Hall, T. L., Hempel, C. R., Wojno, K., Xu, Z., Cain, C. A. & Roberts, W. W. Histotripsy of the prostate: dose effects in a chronic canine model. Urology. 74, 932-937., (2009). PMC2757508

[4]  Schade, G. R., Styn, N. R., Ives, K. A., Hall, T. L. & Roberts, W. W. Prostate histotripsy: evaluation of prostatic urethral treatment parameters in a canine model. BJU Int 113, 498- 503, (2014). PMC3944657

[5]  Schade, G. R., Keller, J., Ives, K., Cheng, X., Rosol, T. J., Keller, E. & Roberts, W. W. Histotripsy Focal Ablation of Implanted Prostate Tumor in an ACE-1 Canine Cancer Model. The Journal of Urology 188, 1957-1964, (2012).

[6]  Styn, N. R., Hall, T. L., Fowlkes, J. B., Cain, C. A. & Roberts, W. W. Histotripsy of renal implanted VX-2 tumor in a rabbit model: investigation of metastases. Urology 80, 724- 729, (2012).

[7]  Hall, T. L., Kieran, K., Ives, K., Fowlkes, J. B., Cain, C. A. & Roberts, W. W. Histotripsy of rabbit renal tissue in vivo: temporal histologic trends. Journal of endourology / Endourological Society 21, 1159-1166, (2007).

[8]  Qu, S., Worlikar, T., Felsted, A. E., Ganguly, A., Beems, M. V., Hubbard, R., Pepple, A. L., Kevelin, A. A., Garavaglia, H., Dib, J., Toma, M., Huang, H., Tsung, A., Xu, Z. & Cho, C. S. Non-thermal histotripsy tumor ablation promotes abscopal immune responses that enhance cancer immunotherapy. J Immunother Cancer 8, (2020). PMC7057529

[9]  Pepple, A. L., Guy, J. L., McGinnis, R., Felsted, A. E., Song, B., Hubbard, R., Worlikar, T., Garavaglia, H., Dib, J., Chao, H., Boyle, N., Olszewski, M., Xu, Z., Ganguly, A. & Cho, C. S. Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation. Front Immunol 14, 1012799, (2023). PMC9900174

  Schuster, T. G., Wei, J. T., Hendlin, K., Jahnke, R. & Roberts, W. W. Histotripsy Treatment of Benign Prostatic Enlargement Using the Vortx Rx System: Initial Human Safety and Efficacy Outcomes. Urology, (2018).

  Vidal-Jove, J., Serres, X., Vlaisavljevich, E., Cannata, J., Duryea, A., Miller, R., Merino, X., Velat, M., Kam, Y., Bolduan, R., Amaral, J., Hall, T., Xu, Z., Lee, F. T., Jr. & Ziemlewicz, T. J. First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study. Int. J. Hyperthermia 39, 1115-1123, (2022).

  Vidal-Jove, J., Serres-Creixams, X., Ziemlewicz, T. J. & Cannata, J. M. Liver Histotripsy Mediated Abscopal Effect-Case Report. IEEE Trans Ultrason Ferroelectr Freq Control 68, 3001-3005, (2021).

  Vlaisavljevich, E., Kim, Y., Allen, S., Owens, G., Pelletier, S., Cain, C., Ives, K. & Xu, Z. Image-guided non-invasive ultrasound liver ablation using histotripsy: feasibility study in an in vivo porcine model. Ultrasound Med. Biol. 39, 1398-1409, (2013). 3709011

  Vlaisavljevich, E., Owens, G., Lundt, J., Teofilovic, D., Ives, K., Duryea, A., Bertolina, J., Welling, T. H. & Xu, Z. Non-Invasive Liver Ablation Using Histotripsy: Preclinical Safety Study in an In Vivo Porcine Model. Ultrasound Med. Biol. 43, 1237-1251, (2017).

  Kim, Y., Vlaisavljevich, E., Owens, G. E., Allen, S. P., Cain, C. A. & Xu, Z. In vivo transcostal histotripsy therapy without aberration correction. Phys. Med. Biol. 59, 2553- 2568, (2014).






In conclusion, we have qualitatively and quantitatively demonstrated that histotripsy treatment triggers the release of HER2 from the tumor cells into the extracellular compartment. The histotripsy-mediated release of HER2 antigens provides important insights into the mechanism underlying its immunostimulation and suggests the potential of TSA/TAA-based immunotherapies in numerous cancer types.

Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers

by   1,†,  2,†,  1,  1,  2 and  1,*
1
Department of Internal Medicine, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, MI 48109, USA
2
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
*
Author to whom correspondence should be addressed.
†
These authors have contributed equally to this work.
Cancers 2025, 17(2), 183; https://doi.org/10.3390/cancers17020183
Submission received: 17 December 2024 / Revised: 31 December 2024 / Accepted: 2 January 2025 / Published: 8 January 2025
(This article belongs to the Section Molecular Cancer Biology)
 
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Review Reports Versions Notes

Simple Summary

Histotripsy is a novel non-invasive ultrasound therapy that mechanically breaks down the target tissue into acellular debris. Histotripsy has been shown to stimulate potent immune response and results in an abscopal effect in rodent tumor models and human case reports. It is hypothesized that the primary mechanism underlying histotripsy immunostimulation is the increased release of tumor antigens by the mechanical disruption of the tumor cell membrane without heating or ionization. This is the first study to quantitatively characterize tumor antigen release and show how it is changed by varying histotripsy dose delivery. Mouse mammary breast tumors were treated with histotripsy, and the extracellular HER2 protein, a key breast tumor antigen, was measured. Regarding extracellular HER2 proteins released from in vitro tumor cells, ex vivo or in vivo tumors by histotripsy had significantly higher levels than untreated cases and depended on the histotripsy dose. These findings provide the first quantitative data on the impact of histotripsy on tumor-associated antigen release and provide important insights into histotripsy immunostimulation.

Abstract

Background/Objectives: There is increasing evidence to indicate that histotripsy treatment can enhance the host anti-tumor immune responses both locally at the targeting tumor site as well as systemically from abscopal effects. Histotripsy is a non-invasive ultrasound ablation technology that mechanically disrupts target tissue via cavitation. A key factor contributing to histotripsy-induced abscopal effects is believed to be the release of tumor-specific antigens (TSAs) or tumor-associated antigens (TAAs) that induce a systemic immune response. In this study, we studied the effect of histotripsy treatment on the release of HER2, a well-defined TAA target for cancer immunotherapy. Methods: A range of doses of histotripsy administered to HER2-postive mammary tumor cells in an in vitro cell culture system and an ex vivo tumor were applied. In addition, a single dose of histotripsy was used for an in vivo murine tumor model. The released proteins, and specifically HER2, in both tumor cell-free supernatants and tumor cell pellets were analyzed by a BCA protein assay, an ultra-performance liquid chromatography (UPLC) assay, and Western blot. Results: Our results showed that histotripsy could significantly trigger the release of HER2 proteins in the current study. The level of HER2 proteins was actually higher in tumor cell-free supernatants than in tumor cell pellets, suggesting that HER2 was released from the intracellular domain into the extracellular compartment. Furthermore, proportionally more HER2 protein was released at higher histotripsy doses, indicating free HER2 was histotripsy-dose-dependent. Conclusions: In conclusion, we have qualitatively and quantitatively demonstrated that histotripsy treatment triggers the release of HER2 from the tumor cells into the extracellular compartment. The histotripsy-mediated release of HER2 antigens provides important insights into the mechanism underlying its immunostimulation and suggests the potential of TSA/TAA-based immunotherapies in numerous cancer types.

Table of Contents

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MDPI and ACS Style

Tang, S.; McGinnis, R.; Cao, Z.; Baker, J.R., Jr.; Xu, Z.; Wang, S. Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers. Cancers 2025, 17, 183. https://doi.org/10.3390/cancers17020183

AMA Style

Tang S, McGinnis R, Cao Z, Baker JR Jr., Xu Z, Wang S. Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers. Cancers. 2025; 17(2):183. https://doi.org/10.3390/cancers17020183

Chicago/Turabian Style

Tang, Shengzhuang, Reliza McGinnis, Zhengyi Cao, James R. Baker, Jr., Zhen Xu, and Suhe Wang. 2025. "Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers" Cancers 17, no. 2: 183. https://doi.org/10.3390/cancers17020183

APA Style

Tang, S., McGinnis, R., Cao, Z., Baker, J. R., Jr., Xu, Z., & Wang, S. (2025). Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers. Cancers, 17(2), 183. https://doi.org/10.3390/cancers17020183

histotripsy, Edison, Teresa studie, ultra sound, gasbellen, levertumoren, uitzaaiingen, borstkanker, darmkanker, allveesklierkanker, longkanker, solide tumoren, FDA goedgekeurd


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