The hosts walk through the HOPE4LIVER single-arm pivotal trial, a multi-institution study testing histotripsy on primary and metastatic liver tumors. They describe how the engineering evolved into a full clinical system with an ultrasound transducer, imaging probe, planning software, and a robotic arm, and how technical success was defined as the treatment zone fully covering the tumor on MRI or contrast CT within 36 hours. Using a figure from the paper showing a small metastatic colorectal tumor, they explain how nearby blood vessels were left intact while the targeted tissue broke down and then shrank over 30 days as the body repaired the treated zone.
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The trial reported roughly 95% technical success across 44 patients, with about 7% experiencing major treatment-related complications.
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That complication rate was below the threshold used when the FDA granted de novo clearance for liver tumor destruction in 2023.
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The hosts note a key limitation: the method depends on being able to image the tumor clearly, which is not possible for all liver tumor locations.
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In 2025 HistoSonics was valued at about 2.25 billion dollars in a management-led transaction, which the hosts flag as separate from any personal payout to the inventing scientist.
1,060 words · auto-generated from the episode video
37:23the hope for liver single arm pivotal trial for hystootropsy of primary and metastas metastatic sorry metastatic liver tumors. she was a co-author. This is a multi-institution study. Um, and the engineering now has changed form, >> right? We started from >> just making holes to now we're doing there's a clinical transducer. There's an ultrasound imaging probe for targeting. There's a software to describe the treatment volume. There's a robotic arm that moves the focus through that volume. This is crazy. They've got like the thing that is doing the ultrasound is like moving around in a robotic arm to like target stuff. Um, and each tiny focal treatment has to be
38:04assembled into a threedimensional area that covers um a tumor that is in the liver. >> So, and this we're now getting to let's let's make this work for people. >> Exactly. Yeah. So, you there's like margins that you have to plan. There's nearby structures that you got to avoid. This is now an intact like human being. >> Yeah. >> Okay. This is this is the real deal. like um and the technical success success the definition of technical success is whether the resulting treatment zone completely covered the intended tumor volume on the contrast enhanced CT or the MRI within 36 hours like I do the treatment and within 36 hours when I take the MRI
38:46do I see the effect right well let's see let's see let's see if we do in fact we do so this is figure four from their paper. It shows a 1.3 cm metastatic colurectal cancer in segment 3 of the liver. That's the white arrow on the top left. Yeah, >> there's a little tiny tumor there. >> Okay. Um these are MRI scans. So in B, this is 36 hours post procedure. The treatment zone is in the solid arrow encompassing the side of the tumor and there's a margin. Crucially, the smaller arrow there, that's a blood vessel that traverses the treatment zone. >> It hasn't been
39:29killed. >> Yeah. Yeah. Yeah. Yeah. >> Okay. The traffic is still flowing. >> The Yeah, we we just took part of took apart the riff raff around it, but the traffic of the blood is still flowing through that. And then in part C, this is 30 days postprocedure. It shows involution of the treatment zone. Meaning the the giant hole that you made has gotten smaller. There is recovery happening within the tissue. >> Yeah. Yeah. We we the the region we've targeted is now repairing and we still have our traffic flow. >> Yes. Exactly. Um it's it's it's an incredible story. I think I mean it's incredible for so you know obviously so
40:09many people in every you know many listeners um are less than two or three degrees of separation away from someone who deals with or has suffered from cancer actively or in the past. >> Yeah. And obviously this has been an area that has had in incredible amounts of human scientific research as well as financial backing to try to find ways to deal with. There's so many interesting aspects of this area of research that again the construction the building of oh hey this methodology has functional benefit. Oh,
40:52hey, it also has this like secondary outcome of increased immune response. >> Oh, hey, we can actually do it in humanike contexts. >> Oh, and now when we get to the point where we have to do this in a very precise way for clinical outcomes, when we look to see the results, we are seeing that what we thought was maybe possible at the beginning of this journey is proving to be true. Yeah, >> it's just >> it's incredible. And I mean I I don't want to oversell this thing. I do want I do want to say that you know cancer is an extremely >> 100%. >> Multiaceted disease ailment. Um you know
41:3495% they had 95% success. Um three out of the 44 patients actually did have major complications related to the surgery. So something like 7% had major major complications. Um, and one of the limitations of this is that you need to be able to image this tumor in the first place very very well. There's some tumors where it's like impossible to image because based on their placement and where they are and so on and so forth, right? So, but in its limited capacity, it could be doing wonders, right? It could be it could be the next step. And the the the the treatment for cancer in the future is never going to be a one
42:15>> right >> one thing rules them all right unless we finally like everyone gets genetic engineering somehow right like and and we all live in gatka and it's like mandatory other than that scenario like >> dealing with cancer is going to be a multiaceted there's going to be imunotherapy drugs there's going to be like chemo is always going to be around I think so But more and more tools are necessary, right? And more and more tricks that we have. The better tricks we have, the better it is. Um, in 2023, hystoics uh received US FDA denovo clearance for destruction of liver tumors based on
42:55this study because even that 7% that was like lower than the threshold that is required for the FDA to approve something. Um and this marked a clinical application of this technology developed through Shu's collaboration with these engineers, physicians, and many other researchers. This 2024 trial helps explain the evidence behind that step. Right? And this explains why now the FDA is approving this. In 2025, his sonics announced a managementled transaction valuing the company at approximately 2.25 billion. That's billion with a B. >> With a B. >> Yeah. With a B. That's the company evaluation. I don't think it's a measure of any scientist personally and how much
43:35they earned. I don't think Zu earned like a giant significant portion of that. Um, >> which is problematic, but that's for another episode. >> Yeah, exactly. But it's one sign that, you know, this approach that can begin as a difficult laboratory question, it now sits as a real medical and commercial ecosystem.
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