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Puzzling Out Liver Directed Therapies · The Eye Believe Podcast

0:00
hi Omies and everybody else who is listening in
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our audience today
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thank you so much for registering for our first
0:06
Eye on the Expert Webinar
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here with A Cure In Sight
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I'm Danet Peterson I'm your host
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and I am joined today with 4 doctors
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who are thrilled to be
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talking about some of the newest liver directed
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therapies that are available right now
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to us as uveal melanoma patients
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so you know just as a heads up
0:21
this is gonna be heavily metastatic discussion
0:24
if that's not a topic that you find
0:25
that you can handle right now
0:27
this is being recorded
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and you can come back to this at a later date
0:30
with that
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I'm gonna go ahead and introduce our speakers
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who I am so excited
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and we've been planning this for months
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so I'm really grateful to each of these guys
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for being willing to be on
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so first up
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I'm gonna go ahead and bring on Doctor Sid Padia
0:41
he is an interventional radiologist
0:43
from UCLA in California next up
0:46
I have Doctor Vincent Ma and he is a
0:50
medical oncologist from the university of Wisconsin
0:53
If you attended Eye Believe in Scottsdale
0:55
you would have heard him speak a little bit
0:57
so thank you again for being with us Doctor Ma
0:59
Doctor Padia has also been on the podcast
1:00
so if you haven't listened to his episode
1:02
talking about Hepzato kit on the podcast
1:04
head back to the podcast or the YouTube channel
1:06
and make sure to listen
1:07
next up I actually am bringing in two of my doctors
1:11
I feel a little biased here
1:13
but I mean
1:14
I'm just lucky to have some really good connections
1:15
you guys so
1:16
I've got Doctor Kevin Burns from the
1:19
Providence Mission Hospital
1:20
who's also an interventional radiologist and finally
1:24
Doctor Justin Moser who is the medical oncologist lead
1:28
in uveal melanoma in the Scottsdale
1:29
Arizona area at Honor Health Research Institute
1:33
so thank you guys for being here
1:35
we are here to have a discussion
1:37
so we have a few brief presentations
1:39
like just kind of some basic
1:40
let's let you know what these therapies are right
1:43
so we talked about puzzling out liver
1:44
liver directed therapies
1:46
and we've talked about this webinar
1:47
as we're gonna focus heavily on Histotripsy and Hepzato
1:51
Kit both of which are FDA approved therapies
1:54
one is specific to uveal melanoma
1:56
and is heavily interventional radiology focused
1:59
and then the other one is more general to liver tumors
2:03
so I think I'm gonna go ahead
2:05
and have Doctor Padia go first
2:08
if you wanna pull up
2:09
just kind of give us a brief overview of Hepzato
2:12
like I said before guys he did do an awesome podcast
2:15
and you can go ahead and you can see that podcast um
2:19
and you can see a little more in depth
2:20
but we are gonna talk
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and just have some good discussion here
2:23
thanks Danet and good morning everybody
2:25
so I'm just gonna show a little
2:27
so Danet asked me to speak a little bit about
2:29
a relatively new procedure in
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the United States called Hepzato
2:32
so what is this
2:34
you see a diagram here
2:36
and the goal of this whole device kit
2:40
procedure
2:41
is to saturate the liver with a chemotherapy drug
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the drug is called melphalan
2:48
it's actually quite an old drug that
2:49
several decades old
2:51
and this is designed for people with liver metastases
2:54
specific or uveal melanoma
2:57
it's really only FDA approved for that one indication
3:01
now the difference between
3:02
you know when you normally get chemo
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you often get chemo
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either throw a pill that you swallow
3:06
or through an IV that you get in your arm
3:08
this is very liver specific
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so all the chemo
3:11
about 99% or even higher go straight into the liver
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and there is probably about
3:16
1% of it that distributes in the rest of the body
3:19
so as a result you can give
3:21
very high doses of this chemotherapy called melphalan
3:24
into the liver which can then kill tumors
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so how do we do this
3:27
this is done under anesthesia in the
3:30
in our intervention radology suite in the hospital
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it is completely painless
3:33
because you are under anesthesia
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the procedure itself takes about two and
3:36
two and a half hours
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and what we do is make a bunch of little pinholes
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we barely even use a scalpel
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there's no stitches involved
3:44
we have to put a catheter
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which is think of this as like a hollow bore
3:48
piece of long spaghetti in your upper left thigh
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which you can kind of see on the diagram here
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we use X ray guidance going up into the arteries
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those of the blood vessels going into the liver
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and through that
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we deliver that chemotherapy called melphalan
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at the same time we wanna remove the chemotherapy
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as it percolates through the liver
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so try to picture um
4:11
putting a sponge in your
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under your sink faucet and in the faucets
4:16
running through your sponge
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and it kind of drips out the bottom
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and so we wanna collect all that
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because we want to take it out of the body
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take the chemo out of that blood and then reinsert it
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so that's what this whole circular loop is
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and so we put another small catheter in the vein
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on the patients
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in this case on the patient's right upper thigh
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we withdraw the blood as it's coming out of the liver
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it goes through this
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circuit
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which you can see with these cylinders in this box
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what that does is it extracts the drug out
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and then
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we return the blood back into a vein in the neck
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again through another pinhole
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so during this procedure which does take about
4:55
you know two and a half hours
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so you get multiple pinholes
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and at the end you basically wake up with Band Aids on
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and so that's kind of the procedure in a nutshell
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you'd stay overnight it is
5:06
I would say in general extraordinarily well tolerated
5:10
there's probably a little bit of fatigue for a
5:11
few days afterwards
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and we do have to monitor your blood levels
5:14
throughout the procedure
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but we've had a good amount of experience since April
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2024 which is when it became commercially available in
5:22
the United States and have had very good success rates
5:26
and I'll pass it on Doctor Burns
5:27
if you want to pull up your slides
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I will make it so that you can share yours right
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you should be able to see my slides now so yeah
5:34
I'm gonna talk about Histotripsy
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which is a again also a new procedure
5:39
this was FDA approved in late 2023
5:43
so it's also new on the scene
5:44
and this isn't specific just to uveal melanoma
5:46
this is specific to any liver tumor
5:49
and this is kind of a newer
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groundbreaking thing because it's not invasive
5:53
so think about if you've heard of you know
5:55
external beam radiation
5:56
where they're shooting radiation through your skin to
5:58
to try to target a tumor somewhere
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this is kind of like that
6:01
but we're shooting ultrasound waves in order to
6:03
mechanically destroy a tumor
6:05
so kind of the options of non invasive things really
6:07
it's going to be radiation
6:09
which uses radiation to kill things
6:11
this uses purely mechanical energy
6:14
so the tumor is really liquefied
6:16
and so it's a completely different mechanism of action
6:18
there is one commercially available kit
6:21
one commercial available device which
6:24
which you can see pictured here
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so this is done again
6:27
in an operating room
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and you are completely asleep for this procedure
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as well
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and that is because this can take some time as well
6:33
if you're treating one small tumor
6:35
this procedure can be you know
6:37
less than an hour but oftentimes
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especially in patients with uveal melanoma
6:40
you may have many lesions that we may be targeting
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all during the same procedure
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and so this device here is what's called the Edison
6:47
this is made by a company called HistoSonics
6:49
and so this is a kind of a robotic arm
6:51
it has a ultrasound device built in here
6:53
so we can see live in your liver
6:55
and there's kind of a treatment head here
6:56
it's kind of like a satellite dish
6:58
and I think it kind of
6:59
beams all these ultrasound waves into one
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little focal point
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it's about the size of a grain of rice
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and so we can use ultrasound to target the tumor
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and then on this console here
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we kind of program out what the tumor volume is
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and then we basically
7:11
figure out how much energy we need to deliver
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for your specific body
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and then we turn it on and let it go to work
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treatment times for tumors
7:17
can take anywhere from 4 minutes
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to 1 hour really just depending on the size
7:21
and we can target multiple tumors
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one procedure I think one advantage here is
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this is completely non invasive
7:26
um
7:27
that does not mean that it's not without side effects
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um when we treat one tumor in a patient
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you may have pretty little side effects
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but oftentimes we're treating many tumors now
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because we know that this is safe
7:36
and we can save you multiple procedures
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so it's fairly common to have some
7:40
you know pain
7:41
discomfort kind of at the site
7:42
even though there are no incisions
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so kind of
7:45
a closer look of what this would look like
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on your body so
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a patient can either be lying face up or on their side
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depending on where we need to target
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this Big Water bath is placed on here
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as you know if you've had an ultrasound before
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you know they put that ultrasound gel on the probe
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because you got to get rid of all the air
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or else you can't see into the body
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so there's about 20 liters of water
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this water is run through a special filter
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it's just tap water
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but it takes all the air out of the water
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so there's no bubbles anywhere
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and that allows direct contact from the treatment head
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through the water
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through this membrane here and then into your body
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there's a little video that will play
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um here just kind of showing what this is like
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obviously you kind of
8:20
be asleep for this procedure
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but this is
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kind of what the setup would look like in the room
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and so patient would be asleep on the table
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there's an ultrasound here
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which we can use to first image your liver
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figure out where the tumors are
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and then this is the device here
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so this is how this procedure would work again
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generally this is done under general anesthesia
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although we have done some cases without that
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but currently mostly general anesthesia
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I'm gonna fast forward this video here a little bit
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so this is a simulated patient with one tumor
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so all these ultrasound waves
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converge down to one little point here
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and like I said
8:54
it's about a grain of rice size treatment zone
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so your doctor here can kind of guide the size
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so they're adjusting the size there
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we can use your existing MRI or CT or pet
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and we can actually do fusion imaging
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so we can load that in and match that up
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so the ultrasound will kind of overlay over your
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over your imaging especially if you have a small tumor
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or one that's hard to see
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and then this
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robotic arm kind of guides this treatment through the
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through the tumor and like I said
9:21
if you're treating a you know 2 centimeter tumor
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it may only take four minutes
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once you get everything lined up and planned
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but if you're treating a you know bigger tumor
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it could be over an hour
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it's really a volume dependent here
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so
9:30
this is a simulation of what would be happening inside
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so it's really
9:33
think about this kind of like surgery
9:34
where it's really cutting and going through in
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in mechanically destroying this tissue
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so there's no heat there's no radiation
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which means that we can get
9:41
very close to dangerous things in your liver
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meaning we can treat through blood vessels
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through bile ducts and that's something that we
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may not have been able to do with other
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techniques that go directly through the skin
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and so that's just an overview of what
9:55
Histotripsy is and I'll pause there
10:00
okay awesome
10:03
so I love the visuals and I really think that it helps
10:06
I'm gonna just add a tiny joke
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I had tried to explain
10:09
Hepzato Kit to a family member
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and she told me that she
10:13
she spent the last couple of months thinking that
10:16
the liver soaking
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or this kind of immersing the liver in the melphalan
10:19
involved
10:20
actually taking the liver out
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and putting it in some kind of a basin so um
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that's that was just kind of a fun moment
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I figured you might get a kick out of that Dr Padia
10:29
the one thing is I am not a surgeon so
10:32
we don't do big incisions
10:34
everything is done through pinholes and
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I tell this to patients I'm proud not to do surgery
10:40
so really after the procedure after you wake
10:42
wake up from Anastasia you can go for a walk
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you know there's really no
10:48
you know physical recovery time cause everything is
10:51
you just get band aids it's uh yeah
10:54
so speaking of patients
10:55
or in speaking to patients who have had
10:57
you know either or either of these procedures
10:59
most of the patients that I know have spent
11:02
at least some duration of time
11:04
laying down or resting obviously post recovery
11:07
do you guys have kind of an estimated amount of time
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you know
11:10
that you anticipate
11:11
or does it vary from patient to patient
11:13
and intensity of treatment after the procedure
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typically
11:18
after the procedure that you wake up from anesthesia
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we have a bed rest time about 2 to 3 hours
11:23
it's usually fairly well tolerated
11:25
especially since you are waking up from anesthesia
11:28
and our nurses and ourselves
11:29
we have
11:30
plenty of medications to make people more comfortable
11:32
pain medications, a sedative, etcetera
11:34
to ease that after about 2 hours
11:37
you can walk up and down the hallway
11:40
without any issues
11:42
okay
11:43
Doctor Burns with Histotripsy
11:45
yeah so if uh
11:47
we're treating one tumor
11:49
or tumors where we're going through the front
11:50
so say you're laying on your back
11:52
and we're treating through the front
11:53
and we're not going through the rib cage
11:54
often this is a painless procedure
11:56
some patients
11:57
may complain that the worst part of the day was
12:00
getting the IV when they checked in
12:02
we are doing a lot more aggressive treatments
12:04
now that we have more experience
12:05
meaning that we will be treating through the rib cage
12:07
getting places we weren't going last year
12:09
and that causes some pain
12:12
because the ribs will absorb some of this energy
12:14
we know that we're still being able to treat the tumor
12:16
and we will counsel a patient ahead of time
12:18
knowing that you will experience pain
12:20
after this procedure even though there are no incisions
12:23
in general that is well tolerated
12:25
in any patient we do any
12:27
what's called liver directed therapy
12:29
it's fairly common to have some symptoms
12:31
that usually start the day following
12:33
and we will call this post Histotripsy syndrome
12:35
post ablation syndrome post embolisation syndrome
12:38
truly your body
12:38
having a
12:39
reaction to what is happening inside of your liver
12:42
and that means that you may feel like you have a flu
12:44
a little rundown
12:46
and that generally
12:46
will always start within the first couple days
12:49
usually that's gone by a week
12:50
and some patients experience none of these
12:52
I think it's really a volume issue
12:54
so the more you treat
12:55
the more likely you are to have some of these symptoms
12:57
there are no activity restrictions with this
12:59
because there are no incisions
13:00
there's no wounds you need to recover from
13:02
in fact if you were on a blood thinner for some reason
13:05
we don't even stop that for this procedure
13:07
because there are no incisions
13:08
and if you are on different sort of systemic therapies
13:11
we don't stop or interrupt that
13:12
we do this concurrently with all of those therapies
13:14
so
13:15
especially since this is new
13:17
although it's getting more recognized now
13:19
because we don't have long term evidence
13:22
we can talk to the oncologist and say hey
13:23
we are not gonna stop anything you are doing
13:25
so whatever you are doing is working
13:27
this is really an adjunct
13:28
and maybe this will be synergistic
13:30
okay I do wanna bring our medical oncologist into this
13:33
because I know both of you guys have had at least
13:36
you know
13:36
one or both of you have had a series of patients
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or at least some patients who have had either or
13:42
of these treatments so some of them yeah
13:44
so I guess I know you know people who have had
13:47
and you've treated people who have had Hepzato and
13:49
or Histotripsy so Doctor Ma
13:52
what are you seeing recovery wise
13:54
for the patients that you are
13:55
you know advising to do Hepzato Kit with your team
13:58
yeah no thanks
13:59
I mean
14:00
our center has actually treated a good
14:01
number of patients with Hepzato
14:03
at this point and so I
14:04
you know
14:05
I think what we sort of boast about here is that
14:07
you know
14:07
we actually work very closely with our interventional
14:10
radiology team I think
14:11
communication between the med onc team
14:13
and the IR team is extremely important
14:15
especially from that transition period from
14:17
you know
14:18
post operative recovery to sort of that outpatient
14:21
you know as Doctor Padia mentioned
14:22
you know the recovery is actually surprisingly fairly
14:25
fairly good I mean
14:26
fairly minimal
14:28
patients after the procedure are typically discharged
14:31
you know fairly soon
14:33
quickly as within 24 hours
14:36
and usually the way we do at our center is
14:38
you know from the medical oncology perspective
14:40
we'll actually see these patients
14:42
one to two days post op
14:43
so that we can actually administer a growth factor
14:46
cause
14:46
we do anticipate
14:47
after administration of the melphalan to the liver
14:50
that they do get some of these residual effects
14:52
that actually affect the bone marrow
14:54
may actually can cause
14:55
you know a decrease in white blood cells
14:58
so we do administer the growth factor
15:00
typically on day 2 or day 3 after the procedure
15:03
and then you know
15:04
we sort of take over from the med onc perspective
15:06
where we actually monitor the patient's blood counts
15:09
typically weekly
15:10
anywhere from two to four weeks post procedure
15:14
but for the most part I have to say
15:16
you know
15:16
when we see our patients after treatment with Hepzato
15:19
the recovery is exceptional
15:20
there's fairly minimal in terms of pain
15:24
nausea vomiting
15:25
patients actually for the most part
15:27
get back to their sort of normal routine
15:29
until they get onto sort of the next cycle of therapy
15:33
awesome Doctor Moser
15:34
what do you have to add yeah
15:36
I want to echo you know
15:37
what Vin said is when you think about Hepzato
15:40
and we talk about isolating the liver and
15:42
you know putting
15:43
like circulating high dose chemotherapy through it
15:46
it frankly sounds a little barbaric right
15:49
and so I think a lot of the times we think oh
15:51
this is gonna be rough
15:52
and I know when we started offering it at our center
15:54
we were a little nervous but I think
15:56
our experience is similar to that of Doctor Padia
15:58
and Doctor Ma which is
15:59
this is actually a really well tolerated procedure
16:02
you know it is not nearly as barbaric
16:04
it's actually very few side effects
16:07
but
16:07
I do think
16:08
the lying flat thing is probably the biggest issue
16:11
we have even though it's a very minor thing right
16:13
a lot of my patients I think our internal protocols are
16:16
once we pull the sheets from the pinholes in the legs
16:19
they need to lie flat for four hours
16:21
and that frankly is just boredom
16:23
and it's just fighting that boredom
16:24
so some people you know
16:25
most of my patients like
16:27
they bring their headphones
16:28
and they listen to podcasts
16:29
or they have books on audio or something
16:31
just to kind of get them through that boredom
16:33
of not being able to move
16:35
but other than that
16:35
it's a really well tolerated procedure despite the
16:39
how intense it seems kind of on paper
16:41
or as you describe it I agree with Doctor Moser that
16:45
you know the first time before
16:46
and I'm the guy who does
16:47
these before the first one I was like
16:51
this seems like a lot and you know
16:54
we're washing the liver with this high dose chemo
16:57
I'm very curious
16:59
and I'm a little bit doubtful as to how patients
17:01
are gonna tolerate it
17:02
so the first one where we did she tolerated really well
17:05
I'm like okay maybe that was just a fluke
17:07
maybe we just got lucky and then the second one
17:08
third one fourth one as the guy who's doing it
17:11
I'm also quite surprised at how well tolerated it is
17:14
because it is quite involved
17:16
but the patient recovery
17:17
my recovery instructions are this
17:19
you know for example
17:20
I have two patients coming in on Monday
17:22
I say take the week off of work
17:24
that's it by the following Monday
17:27
you can get back to whatever job you're doing
17:29
whether you're you know
17:30
working in the office or or doing a construction job
17:32
you know you take a couple of days off and you're
17:34
you're back to you know kind of near
17:37
your baseline so as far as Histotripsy goes
17:39
then on kind of maybe the
17:41
I don't wanna say the other side
17:42
you guys because we're not here to pit these
17:43
therapies against each other
17:45
like Doctor Kevin said
17:46
this is kind of the idea that this could be adjunct
17:48
and I you know
17:49
I've had conversations with medical oncologist
17:51
who are exploring the idea of Histotripsy
17:53
because I know that Histotripsy coming up a lot
17:56
more online and maybe that's my fault sorry
17:58
not sorry but
18:00
but I know that
18:01
that it's something that because it's newer
18:03
you know it's approached with that level of
18:06
maybe higher skepticism with the
18:08
you know with the medical oncology teams
18:10
even with the newer interventional radiology teams
18:12
and so I do wanna have
18:14
just a little bit of some dialogue between Doctor
18:16
Padia and Doctor Burns about like
18:18
have you guys kind of run into this you know skepticism
18:21
you know among your team
18:21
among the people that you've met people who practice
18:24
I know
18:25
Doctor Burns is probably the one who has done the most
18:27
Histotripsy procedures
18:29
I don't know where your count is on uveal
18:31
melanoma patients
18:32
but I know you've done a good number of them
18:34
at least in the last year ish
18:38
I'll say I think
18:39
maybe we should talk about the indications
18:40
for these procedures because I think they're different
18:42
yeah right
18:42
so these are not competing therapies
18:44
I think they're different
18:46
so Histotripsy is a focal therapy right
18:49
so if you have
18:51
if you have a small number of tumors that we can count
18:54
and that we can see
18:55
then that may be a good indication for Histotripsy
18:57
so if you had three liver tumors
18:59
and we can go in
19:00
and treat each of them with histotypsy
19:02
maybe that is a beneficial therapy for you
19:04
because we can
19:05
avoid damaging any of the rest of your liver
19:07
so when we do this therapy
19:08
as you think these waves go through
19:09
they don't damage the liver on the way in
19:11
or the way out um
19:12
and so it's really a focal treatment and
19:15
but if you presented to me and you had what
19:18
if you read an report
19:19
innumerable lesions or small lesions
19:21
that is maybe not the indication for Histotripsy
19:23
maybe that is where the Hepzato Kit comes in
19:26
so I think these are at two ends of a spectrum
19:28
of different types of patients
19:30
that all are
19:31
uveal melanoma patients completely agree with Kevin
19:33
these are not really meant to compete with each other
19:36
someone with a single tumor
19:38
I don't offer Hepzato
19:40
we have a lot of options for a single tumor
19:42
Histotripsy one of them
19:43
we can do an ablation
19:44
we can do a Y90 radio embolization
19:46
the advantage or let's say disadvantage
19:49
of a Hepzato procedure
19:50
is that we treat the entire liver
19:52
and so we'll give you two scenarios
19:55
one let's say
19:55
a single person has one focal tumor that's 1 inch wide
20:00
you know
20:00
the size of a golf ball on the corner of their liver
20:03
why would I use any therapy to treat the entire liver
20:06
if it's one isolated thing
20:07
cause we wanna save that therapy for if
20:10
and hopefully never
20:11
but if that patient gets multiple tumors in the future
20:15
in contrast you look at the other side of spectrum
20:17
let's say most
20:17
of the people I'm treating have more than five
20:20
many of them have and Doctor Ma
20:22
and Doctor Moser have seen a lot of these patients
20:24
they have 20 30
20:25
sometimes you can't count
20:27
or you'll spend five hours counting on
20:29
on a CT scan and in that case
20:31
you need a much more global type of treatment as
20:34
as many of the listeners know
20:36
uveal melanoma is one of the few cancers where
20:38
in 99% of these
20:40
with liver metasies that really localize the liver
20:42
so that's why we make this argument that
20:44
you know
20:44
the liver directed therapy may help these patients
20:48
the Hepzato was designed to treat the entire liver
20:49
from one edge to the other
20:51
it saturates it just like the sponge analogy
20:54
you put the
20:55
the sponge on your kitchen sink
20:56
you run the water and you know your
20:58
your whole sponge will fill up
20:59
and so the indications do tend to be
21:02
I would say for the vast majority patient
21:04
non overlapping between the two types of procedures
21:09
Doctor Moser
21:10
I know you wanted to jump in as well
21:11
do you wanna weigh in
21:12
kind of on what you've seen between the two
21:14
yeah I think they are kind of different treatments
21:16
right
21:16
it's a spot treatment versus a whole liver treatment
21:18
and you know
21:19
I think the biggest thing we gotta remember is
21:22
having more tools for the liver is the best option
21:24
for our patients it's the liver
21:25
metastases in patients that have uveal malanoma
21:28
that causes problems it causes liver issues
21:30
it can cause you know
21:32
swelling in the belly
21:33
and so having more tools to manage the liver is great
21:37
but when we're comparing them
21:39
I also think
21:40
we got to remember that both of these are new
21:42
and we're still learning a ton
21:44
you know the Hepzato trial was a 50
21:47
60 patient trial that treated patients with
21:50
predominantly liver only disease
21:52
now a lot of us are using Hepzato
21:53
and non liver only disease because again
21:56
we need to control the liver
21:57
and with that trial we have both response rates
22:00
how much the tumor shrinks
22:02
but also overall survival
22:04
and progression free survival data
22:06
with Histo which is the newest thing and frankly cool
22:10
it's almost SCI fi right
22:11
of how it uses sound waves to kind of destroy stuff
22:14
that was approved for any tumor with
22:16
or any liver metastasis
22:18
based on a trial of 40 some patients
22:20
of which two were uveal malanoma
22:23
and the primary endpoint of that study was
22:26
did you hit your target
22:28
and did it look dead within 36 hours
22:30
and so you know
22:32
I use Hepzato or I use histo
22:34
Kevin's treated a couple of my patients now
22:36
because I do think there is a role for spot treatments
22:39
we also need to be aware of the data
22:41
you know
22:41
we don't have quite as much durability information
22:44
about Histo as we do Hepzato
22:47
although the Hepzato data is still small
22:49
so definitely
22:50
I think they're set with non overlapping indications
22:53
do I need to treat the whole liver or 2 to 3
22:55
but I think for patients who are in the middle
22:57
who have maybe 3 or 4 lesions that could get both
23:00
my preference is still Hepzato
23:02
just cause we have a slightly more data now
23:05
that could change in a year
23:06
once we get more data it could be Histo is better
23:09
but right now I think of the limited data we have
23:11
if it's on the fence Hepzato first
23:14
for patients who are willing to undergo intervention
23:17
right if someone says I don't want anything invasive
23:19
but I'm still willing to do general anesthesia
23:21
then Histo is not wrong
23:23
we're both interventional radiologists
23:24
I'll just add so we do a lot of other procedures also
23:27
so Sid had mentioned microwave ablation
23:30
that has decades of research
23:33
and so we have all these other tools
23:35
we're talking about two of them today
23:37
but we have all these other tools
23:38
he had mentioned Y90 as well
23:40
which have long term data
23:41
there's definitely options
23:43
that we also have that do have some longer term data
23:45
we're just talking about the cool new stuff
23:47
the nice thing is so far we don't have
23:50
we have not found
23:51
bad interactions with systemic therapy
23:54
because if we did then it becomes a bigger challenge
23:57
right if I have to take someone off of what
24:00
I'll give you one example
24:01
let's say I have to take someone off of tebentatusp
24:03
also known as kimmtrak which is used in
24:06
you know
24:06
almost half of patients with metastatic uveal melanoma
24:10
if I have to tell a patient
24:11
you have to go off of this so I can do this
24:14
it's not that easy of a discussion because
24:16
you know what are you gonna do
24:18
how to
24:18
you take someone off this drug and then their tumors
24:21
you know grow rapidly
24:22
so as far as we can tell
24:24
and it's always challenging with a new therapy
24:26
because we haven't done 10,000 people yet
24:29
I have not seen any or nor heard of any
24:32
really bad interactions with the standard of care
24:35
systemic therapies that are used for uveal melanoma
24:39
Doctor Moser and Doctor Ma
24:40
have you guys seen any bad interactions so far
24:43
no it's great that you actually bring that up as well
24:45
because these are
24:46
some of the conversations I have with my patients
24:48
as well when they're diagnosed with metastatic
24:50
uveal melanoma you know
24:51
we're sort of in that dilemma
24:52
do we sort of focus purely on the liver
24:55
or do we need to kind of think of it more of
24:56
on a systemic level right
24:58
you know for the vast majority of patients
25:00
with uveal melanoma
25:01
they just may present with only liver disease
25:04
and so it may make sense to just
25:05
kind of focus on just treating the liver itself
25:08
but when you're sort of thinking about
25:09
sort of along lines of Histotripsy
25:11
where you're maybe thinking about treating maybe one
25:13
or even a few number of liver mets
25:17
you kind of have to think to yourself
25:18
well what about the other parts of the liver
25:20
where you can't physically see disease
25:23
you know
25:23
there's that possibility that there may be sort of
25:25
microscopic disease where you sort of
25:27
need to think about incorporating some degree of
25:30
you know systemic therapy alongside it
25:33
you know whereas Hepzato
25:34
you know you sort of have that opportunity to kind of
25:35
saturate the whole liver and you sort of hope that
25:38
that is the only site of disease that's present
25:40
you know from the melanoma
25:42
so you know
25:43
these are sort of the tug and pull
25:44
and sort of having to weigh the risks
25:46
and the benefits of choosing either one procedure
25:48
but you know
25:49
when it comes to patients
25:50
for example who may not
25:51
for example be fit enough
25:53
you know where
25:54
you know handling sort of the hemodynamic
25:57
instability that frequently occurs with Hepzato
26:00
you know
26:00
Histotripsy might be a really great option to certainly
26:02
consider for those patients
26:04
you know in those particular cases
26:06
I may as an oncologist
26:07
want to think about also incorporating systemic therapy
26:10
concurrently you know
26:11
in hearing from Doctor Burns
26:12
hearing that you know
26:13
doing Histotripsy doesn't necessarily forbid you
26:16
or as a medical oncologist
26:17
to give systemic therapy is also a very
26:19
feasible and
26:20
and a great option to sort of hear about as well yeah
26:23
just to go back to what you Doctor Moss said you know
26:26
for the Hepzato of which I forgot to mention
26:27
you don't
26:28
you are under anesthesia and during the anesthesia
26:30
but during the procedure
26:31
your blood pressure can vary quite a bit
26:33
and so what we do is before they're even scheduled
26:36
we get
26:37
they get a stress test to make sure that we don't
26:40
you know we're not looking for
26:41
people who have a lot of cardiovascular disease
26:43
about people with heart attacks and strokes
26:45
you know you're really not a candidate for this
26:46
we wanna make sure that you can tolerate the procedure
26:49
you know intraoperatively during the procedure
26:52
we wanna make sure that your blood pressure
26:54
can tolerate it so as an example
26:56
if you have a I don't know
26:57
an 85 year old who can walk three blocks
26:59
and then gets chest pain
27:00
they're not a good candidate for this
27:03
the last thing we need to do is have some kind of
27:04
terrible cardiac
27:05
or heart or brain complication from the anaesthetic
27:09
hmm such good points okay
27:12
you guys we are getting innuerable questions
27:15
and this is great because this means we have people
27:17
who are really interested in advocating for themselves
27:19
and who wanna learn so you guys who are on listening
27:22
I'm so proud of you guys for being here
27:23
for asking questions we're gonna do
27:25
the best that we can to answer these questions
27:27
I am gonna say some of them I think we have addressed
27:30
like I think there's been the
27:31
the question about
27:33
concurrent treatment with other immunotherapy
27:35
that's been addressed pretty well
27:36
I think the general consensus is yes
27:38
like you can continue systemic therapy
27:41
under the guidance of your medical oncologist
27:43
however we do have this question is
27:47
can I have Histotripsy if I've had Hepzato previously
27:50
Doctor Burns do you wanna take that one
27:54
yes I will say yes
27:55
you can and you can you can go the other way also
27:57
you can have had a microwave ablation
27:59
you could have had Y90
28:00
all these therapies can be mixed and matched
28:02
obviously
28:04
your doctor will evaluate
28:05
to make sure
28:05
your liver is healthy enough to undergo something
28:07
but all of these I think
28:09
probably
28:09
a patient could have all of these over the course
28:11
of treatment regimen if needed
28:12
the nice thing about all of these is that
28:15
Histotripsy, microwave ablation
28:17
Hepzato, none of them cause liver damage
28:19
I'll be honest I was surprised
28:21
I thought Hepzato would cause liver damage
28:23
or soaking the liver in chemo
28:24
how will it not cause liver damage right
28:26
and every single patient I've had
28:28
their liver enzymes are totally normal afterwards
28:31
so I was a
28:32
honestly a non believer until I started doing it
28:35
Histotripsy same way microwave ablation
28:38
Y90 if done appropriately in the right setting
28:41
also does not cause liver damage
28:43
so yeah we
28:44
we're mixing and matching
28:46
the key thing for us to do over the next
28:48
let's say five years
28:49
is figure out how to best integrate all of these
28:52
as Doctor Moser said
28:53
and it's great now that we have all these tools
28:55
but we really still are learning when to use option A
28:59
when to use option B
28:59
when to switch from option B to option A and option C
29:02
and so on and the more tools we have that
29:04
you know of course
29:05
it's more of a challenge to do that well
29:07
this is why we call this
29:08
puzzling out liver directed therapies right
29:10
I feel like from the first time I've ever heard
29:13
Doctor Moser speak about medical oncology
29:15
and clinical trials like
29:16
he was always really upfront about
29:17
talking about how much of a puzzle each patient is
29:21
individually and that as an oncologist
29:23
as an interventional radiologist
29:25
you know anyone
29:25
potentially part of the tumor board
29:27
who is treating a patient with uveal melanoma
29:29
these patients are individually unique
29:31
no puzzle is the same right
29:33
no puzzle is the same
29:34
and to have all of these potential tools
29:36
these potential ways to fit things together
29:38
is such a gift anyone have anything else they wanna add
29:40
before I move to the next question
29:42
what about SBRT is that
29:43
talking to Doctor Mos or Doctor Ma
29:45
is that something that
29:45
you offer to any of your patients
29:47
certainly a good option that I
29:48
definitely consider I mean
29:49
we have a very strong radiation oncology group here
29:52
Wisconsin and so
29:53
you know often times
29:55
you know before the availability of Hepzato
29:57
and even Histotripsy
29:59
we've actually I personally
30:00
have been utilizing both a radiation therapy
30:02
but also combining it with immunotherapy you know
30:05
we've done some research over the last few years
30:07
that there may be some sort of an abscopal effect
30:10
meaning
30:10
that the effects of radiation therapy in one site
30:13
may actually have an effect elsewhere on the body
30:15
as well and so my belief is that
30:18
you know incorporating
30:19
if you're gonna do radiation therapy to target
30:20
maybe one or even a few liver lesions
30:23
I actually do feel that you know
30:25
incorporation of immunotherapy
30:26
also makes a lot of sense as well
30:29
awesome
30:30
Doctor Burns can I
30:32
can I point out there have
30:33
been a few questions coming through
30:34
that are just asking about
30:35
you know the research and I know doctor
30:38
Doctor Moser and Doctor Padia
30:40
and I think Doctor Ma have all kind of
30:41
alluded to some of the studies around Hepzato
30:44
what can you tell us about what's being studied
30:46
and kind of the data that's coming around Histo
30:48
cause I know that something we all want right
30:49
you know we want the data exactly yeah
30:51
it's when something's new
30:52
you can't have any long term data
30:53
but that's how things work unfortunately
30:54
so this received approval based on a
30:57
limited study of 44 patients
30:58
mainly to show that tumors could be targeted
31:01
and there were no complications
31:02
it was mainly a safety trial as well
31:04
cause if we had a therapy that was really effective
31:07
but it killed half the patients
31:08
that's not a good therapy
31:10
so we want something safe as well as effective
31:12
so there is currently a registry going on
31:14
meaning that it's not a trial that you can enter
31:16
but if you're having the procedure
31:17
you can roll in this trial called boombox
31:19
and that it will be a all comers trial
31:20
to collect date on every single patient
31:23
receiving this therapy at every center
31:25
and so that way
31:25
we can amass a large database of patients
31:28
and put out some publications on long term data
31:30
there have been
31:32
probably over 900 patients treated so far in the US
31:36
and in about a year at our facility here
31:38
we have treated just over 200 patients
31:40
um and so we have quite a big experience of that
31:42
and we are running our own internal studies as well
31:45
to follow our patients
31:46
if they don't qualify for the other
31:48
the other registry
31:49
so that data will probably come out later
31:51
but we have to amass
31:53
I think it's gonna be different based on tumor types
31:55
so we treat many tumor types of this
31:57
we need to get enough tumors in each tumor type
32:00
so I would say uveal melanoma is just more rare
32:03
so it's gonna be uh not as many patients with that
32:06
versus primary liver cancer
32:07
or glandro carcinoma or colon cancer
32:09
so it will take some time for all this data to come out
32:11
if we're talking about local control rates
32:13
we can say
32:14
maybe that will be the same between tumor types
32:16
but maybe it's not
32:18
and speaking of what Doctor Ma has said as well
32:21
about combining immunotherapy
32:22
I think that that will be a role here as well
32:24
because this is think about it similar to radiation
32:27
but now we're not even radiating the tumor
32:29
we're liquifying it so it's a cellular destruction
32:31
not necessarily a molecular destruction
32:33
so there may be some molecules
32:35
antigens that are left inside of this cavity that
32:37
with the immunotherapy
32:38
may provide this abscopal effect as
32:40
as was mentioned before
32:42
that has been shown in animal models again
32:44
that does not translate over to humans all the time
32:46
so there's a lot of unknowns
32:47
I think with with
32:49
with Histotripsy data about the tumor
32:51
specific stuff that you're mentioning Kevin
32:53
is gonna be key right
32:54
cause kind of rolling it into the last question
32:56
about radiation
32:57
tumors have different response rates to radiation
32:59
melanoma is actually considered a
33:01
very radiation resistant like tumor
33:03
it takes higher doses and is less likely
33:05
so I used a lot of radiation before
33:08
we had Hepzato and Histotripsy now
33:10
I mean
33:10
because we couldn't always do an interop ablation
33:13
or an IR guarded
33:14
ablation due to the logistics and invasiveness
33:16
I'm using much less of that now
33:18
because melanoma's radiation resistant
33:20
and so I think for radiation resistant tumors
33:23
these treatments like Histo and Hepzato
33:25
are probably gonna be better than radiation
33:28
we just need the data to confirm that yeah
33:30
so I feel like this goes really well with this question
33:33
and it says it's a little of a complex question
33:35
but why might someone with ocular melanoma
33:36
that's metastasized to the liver
33:38
choose Hepzato over that
33:40
standard radiation for treating liver lesions
33:42
so can we clarify
33:44
this radiation that you're talking about
33:45
because radio frequency ablation
33:48
that's a microwave ablation correct
33:50
and Y90 is I think like kind of like the
33:54
it can be done different ways
33:56
but Doctor Padia has talked to me about how
33:57
like it can be done
33:58
where you kind of explode a tumor from the inside out
34:00
or it can be treating a whole lobe of the liver
34:04
is that the radiation that you're talking about
34:06
or are you talking about different radiation
34:09
I think the first question was on that SBRT
34:11
so stereotactic external beam radiation
34:15
you know to answer the question about I
34:17
I think this person this question is talking about
34:19
more about the Y90 treatment to the liver
34:22
and I think why would you choose Hepzato over that
34:24
and you know Doctor Podia and Doctor Burns there
34:26
it's more IR data so they can weigh in as well
34:29
I think the data is actually better for Hepzato
34:31
the studies for Y90 in uveal are small trials
34:34
they didn't necessarily focus on response rates
34:36
it really was overall survival
34:38
but when you look at the Hepzato data
34:40
that had a higher response rate than what we would
34:42
typically see in uveal
34:43
melanoma patients for anything really
34:46
and
34:47
you know survival of over two years that looks better
34:52
now until we do a head to head comparison
34:54
we can't really say that
34:56
but it looks better and I don't know what Doctor
34:58
Padia and Doctor Burns think about that yeah
35:00
you know
35:01
in the
35:01
it ends up becoming a little bit of a word salad right
35:03
it so this whole radio or radiation
35:06
you know what is that
35:06
so radio frequency ablation does not use any radiation
35:10
it actually works by ionic agitation and heat
35:12
and so on so we're gonna put that one to the side
35:15
so when we talk about radiation
35:16
there's in the liver two forms of radiation
35:19
one is from the outside in
35:20
so you go SBRT which is stereotactic body radiotherapy
35:24
and goes by a bunch of different acronyms
35:26
going to a scanner
35:27
similar to what you've had in a CT scanner
35:28
MRI and some radiation beam shines from the machine
35:32
into your body so it goes right in
35:35
you don't feel it
35:36
and it zaps some body part based on computer modeling
35:38
so that's external beam radiation
35:40
and it goes by a bunch of acronyms
35:41
then there's internal radiation
35:43
where it goes from the inside
35:44
so those are you know
35:45
if maybe even in your eye itself
35:48
when you had uveal melanoma you may have gotten some
35:49
what's called plaque or brachytherapy
35:52
or Y90 is an internal radiation
35:55
where we deliver
35:56
radioactive particles inside the tumor
35:59
through the blood vessels
36:00
and so now you have this golf ball size tumor
36:04
and then the radiation seeds are in the inside of it
36:07
and the nice thing about that is there's no spread
36:10
there are from the Y90 versus the Hepzato
36:13
it's a question we're trying to answer now
36:14
we're making some progress but
36:16
you know give me about two
36:17
three years and I'll have a better answer
36:19
I'd say that the person who has multiple tumors
36:23
in both the right side of the liver
36:25
and left side of the liver
36:25
and Doctor
36:26
Ma made a very important point about 10 minutes ago
36:29
there are also
36:29
sometimes you see these things or you don't see them
36:32
microscopic tumors
36:33
tumors that are too small to see on our cat scan
36:36
and MRI or even on our angiograms
36:38
you know if someone
36:39
for example has 15 tumors
36:41
in all likelihood they have more than 15 right
36:44
it's just that you know
36:45
microscopic deposits here and there
36:47
we don't see them because our machines are man made
36:50
at the end of the day and they have a limitation
36:52
just like your computer monitor
36:54
has a limitation in terms of resolution
36:56
so the Hepzato
36:58
the nice thing is it kind of saturates your whole liver
37:01
the Y90 is meant to be a little bit more focal
37:03
and targeted so currently in 2025
37:07
how am I doing this in our practice
37:08
and again this is not necessarily the right answer
37:10
just kind of if someone needs a whole liver treatment
37:13
we're leading more towards the Hepzato
37:16
assuming they fit all the criteria
37:17
if someone needs a more focal treatment
37:19
let's say
37:19
you have three tumors on the right side of your liver
37:22
but nothing on your left side
37:24
we may consider more of a Y90 procedure where that
37:27
we just target the right side
37:29
treat those with very high doses of radiation
37:32
and we get very good results
37:33
so there's
37:34
when I think about it as a venn diagram
37:37
where you have like a uh
37:38
indications for one indications for another
37:40
there's maybe a little bit of overlap between the two
37:43
and in that overlap is where we're trying to really
37:45
clear up which one is option No. 1 for somebody
37:49
and option No. 2 we're not there yet
37:52
I think it'll take some time
37:53
I have a question around
37:55
the frequency of using these treatments
37:58
and obviously
37:59
we've established these aren't necessarily
38:00
they're not comparative like competing treatments
38:03
these are used in different patients
38:04
for different reasons
38:05
but what are you guys seeing as the
38:07
frequency with which you can use it to treat
38:09
so Doctor Ma Doctor Moser Doctor Padia
38:11
how often do patients have a Hepzato Kit treatment
38:14
what's kind of the protocol
38:16
the standard protocol was developed off of this trial
38:18
called the focus trial so it's a little bit
38:22
admittedly a little bit arbitrary
38:24
and so what what I tell people is that
38:26
you get two Hepzato treatments
38:28
off the bat they're scheduled
38:30
I schedule them in advance
38:32
anywhere from six to eight weeks in general
38:34
so in other words
38:35
today is February 21st so let's say you get one today
38:38
and then you're gonna get one late March
38:39
early April okay
38:41
and then what we do is we get another scan
38:44
a cat scan or an MRI
38:45
one to two months later and see what we're doing
38:47
and if we decide to do another round
38:51
we'll just we do them in twos like another two
38:53
another two
38:53
another two there's a lot of debate and controversy
38:57
so there's no right answer of after that first two
39:01
you know you get in your new scan
39:03
do you go to Hepzato number
39:04
3 and four and
39:07
as interventional radiologists
39:09
of people around the country and around the world
39:11
who are doing this we're all over the map
39:12
we don't know the right answer for that you know
39:15
on the one hand
39:16
we wanna try to kill as much cancer as possible
39:18
on the other hand
39:18
we wanna be able to stretch these therapies out
39:21
as long as possible
39:22
so we're kind of trying to reach that perfect balance
39:26
so we don't I don't have the right answer yet
39:29
okay this is the
39:30
the follow up question to that
39:31
and then I'll ask Doctor Burns
39:32
is there like
39:33
a lifetime number of Hepzato
39:35
treatments that you can have
39:36
like based on you know
39:37
the data that we have or is it like
39:40
for example if you had 1
39:41
2 3
39:42
4 5
39:42
6 in those pairs
39:44
maybe they all happened pretty consecutively
39:46
and then you reach some level of stabilization
39:49
do you then start the clock over a year later
39:51
if you present with new disease
39:53
and now you have 6 more or are you done with Hepzato
39:55
you can't use it again so right now
39:57
the official line is that
39:58
you should get no more than six
40:00
that being said there have been a lot of people
40:02
who have gotten more than that
40:04
it's just that we don't have
40:05
good data to support
40:08
or negate the fact that you can get more
40:09
the 6
40:09
and we always have to think about every time we do this
40:12
what is the potential benefit
40:14
but also what is the potential risk
40:15
so what we
40:16
what people have seen is once you start to get to 6
40:19
Doctor Mosers talked about the
40:21
white blood cell count Doctor Ma did as well
40:23
in terms of supporting people with the white
40:25
you know
40:25
that can get more severe with them for their treatment
40:29
so if we find out treat No. 6 wow
40:32
your white blood cell cans getting really
40:34
really well then
40:35
you know if I do No. 7 and 8
40:36
Doctor Moser and Doctor Ma
40:37
gonna have some problems managing this patient
40:39
because they're gonna start getting infections
40:40
and so on and we don't wanna get that
40:43
yeah so there is a
40:44
there is a tipping point to watch for
40:45
and that's what Doctor Moser
40:46
Doctor Ma
40:47
medical oncology teams are helping to monitor
40:49
that more long term
40:51
do you guys have anything you want to weigh in on
40:52
or do you think we can move to Doctor Burns
40:54
and kind of flip the question for Histo
40:57
no I mean
40:58
I sort of agree with what Doctor Padia mentioned
41:00
I mean as of right now
41:01
when I educate my patients about going through Hepzato
41:04
I usually say up to about 6 cycles of therapy
41:07
you know
41:08
and the reason I do worry
41:09
especially thinking about even going beyond
41:11
you know just six doses of it is
41:13
you know
41:14
thinking about the cumulative effects of the melphalan
41:16
on the bone marrow you know
41:17
I've seen having treated several patients at this point
41:20
that every time we go through a cycle of Hepzato
41:23
the blood counts get much more difficult
41:25
in terms of their recovery
41:26
and so you know
41:27
maybe perhaps down the road
41:29
as we get more data
41:30
and we see more patients being treated with Hepzato
41:32
we can sort of think about the idea of
41:34
even considering giving more cycles of these therapies
41:36
especially as you said after six cycles
41:39
what happens is
41:40
maybe we give the patients a bit of a break
41:42
and then as we repeat scans down the road
41:44
do we need to think about
41:45
giving more of these treatments
41:47
especially if they responded in the beginning
41:49
do we think about giving them again in the future
41:52
but I have to say
41:53
you know the problem is
41:54
as we repeat scans after every two cycles of Hepzato
41:58
you know uveal
41:58
melanoma is a very interesting disease
42:00
that we actually do think nowadays
42:02
that imaging may not be sort of the best
42:04
or most reliable marker
42:06
to know if patients are actually responding
42:08
I mean we can actually see patients who have disease
42:11
that's otherwise very stable
42:13
but they're still benefiting from treatment
42:16
you know for example
42:16
tebentatusp or kimmtrak
42:18
we've learned that the actual shrinkage of tumor
42:21
actually occurs in about less than 10% of patients
42:24
but we know those patients are benefiting from it
42:26
because they're living longer
42:28
than patients who are receiving alternative therapies
42:31
and so those are some of the challenges we face
42:33
especially
42:33
of knowing how our patients benefiting from treatment
42:35
things like Hepzato
42:36
and that may sort of help us one day decide
42:39
do we need to think about actually giving more doses
42:42
this isn't
42:42
a big area of research that we still need to figure out
42:45
yeah Doctor Ma Doctor Moser
42:46
you guys got to get working on finding a better
42:48
like a blood test or something
42:50
tumor marker because I agree
42:51
I mean imaging is is archaic right
42:54
like getting a CT scan every 3 months or MRI
42:57
it's super old school
42:58
we need better and I say this as a radiologist
43:01
we need that should be antiquated
43:04
you guys need to come up with a better blood test
43:05
that
43:05
patients can go to a lab and just get a quick blood draw
43:08
and tell how your cancer is doing
43:09
that's uh I want to come back to that
43:12
I want to come back to that
43:13
because I know Doctor Ma
43:14
and Doctor
43:14
Moser have some interesting things to talk about there
43:17
but for Histotripsy for the same question
43:19
how often can patients
43:20
who present as a good option for spot treatment
43:22
and Histotripsy
43:24
how often are you seeing that you could treat a patient
43:26
Doctor Burns there's really no limits on this
43:29
if it is a focal therapy
43:31
we do have to be cautious of
43:32
destroying too much liver at once
43:34
so if you presented with let's say six tumors
43:39
three in one side three in the other
43:40
and really wanted to undergo Histotripsy
43:43
we would probably stage that therapy treat three
43:45
let's recover for four to six weeks and come back
43:48
we just face these guidelines
43:49
on kind of other things we do
43:50
I don't think there's really any right answers here
43:54
the most sessions we have treated one patient
43:56
we treated many patients over
43:57
four times over the course of a year now
43:59
and those are generally patients with multiple tumors
44:02
new tumors can show up we can go after them
44:04
so and those patients have had
44:06
no impact on their liver function
44:08
as far as we can tell based on laboratory values
44:11
yeah
44:11
we did have a question that I think you answered
44:13
kind of in the back end
44:14
it was just about the AST liver function tests
44:17
so AST ALT any of the liver functionality tests that
44:20
those are evaluated
44:22
what are you seeing in
44:24
kind of a normalization of those levels
44:26
after Histotripsy cause I know
44:27
like some patients experience a little bit of a spike
44:30
and then it comes back down
44:31
I can speak to my experience
44:33
it came back down really fast
44:35
I don't know if it happens with Hepzato
44:36
but when we do anything to destroy liver tissue
44:39
the AST/ALT generally go up
44:40
because think about
44:41
those are like made in the liver cells
44:43
if you destroy a liver cell
44:44
all that gets released and that's what's
44:46
that's what's being detected
44:47
so that can you know
44:49
we measure that on Histotripsy the next day
44:50
I would hope that it's high
44:52
because that means we needed to do
44:53
we have to destroy something in the liver
44:55
and then usually
44:55
those go back to normal fairly quickly
44:57
one or two weeks I wouldn't expect them to be elevated
44:59
for longer than that we have patients who have baseline
45:02
you know mildly elevated LFTS 100
45:04
200 AST/ALT and we have some patients who
45:07
their LFTs normalize afterwards
45:09
I can't explain that
45:11
so and that may not be specific to UM
45:13
but that may be that there is some sort of systemic
45:17
issue going on inside of the liver
45:18
where it's maybe helping deliver globally
45:21
by treating one tumor
45:22
we have not seen after Hepzato your AST/ALT
45:27
and then the other ones are like Bilirubin
45:30
and albumin or 2
45:30
the other ones that measure more of a long term effect
45:33
we have not seen spikes which is great
45:36
I honestly didn't believe it was one of those things
45:38
I was like now we're gonna see a spike
45:39
because as Doctor Burns mentioned
45:40
we're saturating the whole liver
45:41
with its high dose chemo
45:42
how we're not gonna see it for whatever reason
45:44
I don't understand the basic science of it
45:46
but it does not seem to
45:49
the chemo that's used in Hepzato
45:50
does not seem to attack the normal liver cells
45:54
and I'm sure there are medical
45:56
oncologists
45:56
who could explain that way better than I can
45:58
and so let's say even the next day
46:00
when we get a full blood panel
46:02
their liver enzymes are basically the same
46:05
so that's one thing fortunately
46:07
I don't worry about what I do worry about
46:10
is the person who has elevated liver
46:13
blood tests before the procedure
46:16
that is always concerning
46:17
is that a side effect from their drug
46:19
is that a issue
46:20
because they have too much tumor in their liver
46:23
or is it
46:24
are they blocking their bile ducts
46:25
those are the ones where we really
46:27
worry and debate about
46:30
yeah
46:30
and those patients who have the elevated liver enzymes
46:32
are the ones that maybe we direct more towards Histo
46:34
or the spot treatments
46:36
versus the total liver treatment
46:37
cause it's not necessarily
46:38
like you mentioned Doctor Padia
46:40
the drug harming the liver
46:41
but is the liver healthy enough to treat them
46:44
agree yeah
46:45
well and to kind of add to that
46:47
one of the other potentials here is that
46:48
maybe you're treating with Hepzato right
46:50
and you're seeing good response
46:52
and there's some good success there
46:53
but there's a rogue tumor that just keeps kind of
46:55
flaring up or it's just continuing to grow
46:58
despite everything else responding well
47:00
that might be an area where
47:02
you know
47:02
you put Histo or you put Y90 back on the table but
47:05
but specifically that you try to aim to do something
47:07
maybe a little less invasive
47:08
a little less damaging
47:10
with the aim of just treating something unique until
47:12
you know something very specific
47:14
this question I think is a doctor Burns question
47:16
how many tumors can you handle
47:17
once in a treatment or does it really
47:19
I mean you I know this is an oblique question yeah
47:22
I would say it's more
47:23
we have some volume limitations now
47:25
so if you had one very large tumor
47:27
that may be all we treat
47:28
but if you have five small tumors
47:30
you may treat all those at the same time
47:31
I think it's gonna really to be
47:33
depend on
47:34
how many different positions you need to be in
47:35
for the procedure
47:36
how long we think this procedure is gonna take
47:38
obviously
47:38
we don't want you to be sleep the entire day
47:41
cause we can stage these sort of uh procedures
47:43
so I would say there's not really a limit
47:46
but
47:47
there are some complications that can happen with any
47:49
procedure
47:50
and those usually happen when you do too much
47:52
at any one time
47:52
so we would say we want to limit the volume
47:56
if you have this procedure
47:57
we've seen especially just
47:58
I'll just generalize to melanoma in general
48:00
it's fairly common to have
48:01
urine changes after this procedure
48:03
so you can have a dark urine
48:05
immediately after this procedure
48:07
we've seen that associated with very large volume
48:10
treatments of any tumor type
48:12
but we have patients where we treat one
48:14
uveal melanoma lesion and they can have
48:17
red urine
48:18
or dark urine immediately after the procedure
48:19
so there is something excreted renally
48:22
some of the metabolites or the the killed cells
48:25
and so we
48:25
don't wanna saturate the kidneys with anything
48:27
cause we can always stage this and do more overtime
48:30
fortunately
48:31
all that resolves usually you just have you hydrate
48:33
give you some IV fluids
48:34
and usually the next day your urine is clear
48:36
so
48:36
we can run into some complications
48:38
that are extremely rare
48:39
if we do too much at any one time
48:40
speaking of UM
48:41
or UM patients do you have
48:43
like
48:43
a rough count of how many uveal melanoma patients
48:45
you've treated thus far
48:46
Doctor Burns and I don't I mean
48:49
it's gonna be in gathering that data
48:51
probably the 10 to 20 range
48:53
you know I think it's not that many
48:55
and like I said
48:56
it's a more rare disease maybe around the 20 mark now
49:00
but again we've treated about 200 here
49:02
and there's been 900 treated globally
49:04
so maybe the rough number is
49:06
you know there's no way
49:08
there's no way
49:08
there's been more than 50 patients in the world
49:09
treated with this condition so far okay
49:13
this is a good question
49:14
would you treat a single liver lesion
49:17
if it has been stable for greater than 2 years
49:19
on tebentafusp I guess this is a global question
49:22
I guess you know you guys could all weigh in like yes
49:24
no why not
49:26
would there be oh wait Dr Ma
49:27
this would be a great time to bring in CT DNA
49:31
yeah uh
49:32
that's a that's a great question I mean
49:34
so I think the dilemma that I would face
49:36
especially
49:37
if I'm gonna be monitoring the patients on Kimmtrak
49:39
right or tebentafusp
49:41
you know they're on treatment for two years right
49:43
but there's this little
49:43
pesky lesion that we just don't know
49:45
is it indeed you know
49:46
an active or live melanoma
49:49
you know could it potentially even be a scar right
49:51
you know these are sort of the situations
49:53
you know I sort of think about as well
49:54
you know do we need to think
49:55
for example not just even
49:56
you know just doing radiation therapy
49:58
Histotripsy
49:59
or any sort of like focal liver directed therapy
50:02
but maybe even surgery to actually remove it
50:04
and then that might potentially be
50:07
you know an opportunity to even render the patient
50:09
hopefully disease free
50:11
but those are the things I think about as well
50:12
but some of the other tools that I've been so more
50:15
so heavily utilizing over the years
50:17
is actually assessing the patient's blood
50:20
and actually
50:21
assessing a thing called circulating tumor DNA so
50:24
you know as you know
50:25
every part of our body you know
50:26
makes DNA as well as our cancer
50:28
but our cancer secretes a particular DNA
50:31
mutation that is very unique to the tumor itself
50:34
and nowadays
50:35
we have newer and sophisticated technology
50:37
where we can actually detect it in the blood
50:39
and actually monitor it over time
50:41
whether you're using it to monitor and survey patients
50:44
for cancer coming back
50:46
or as an alternative approach
50:47
is actually using it to actually detect
50:50
you know how that level changes over time
50:52
while you're on therapy and so nowadays
50:55
there's actually a variety of different
50:56
commercially available CT
50:58
or circulating tumor DNA tests available
51:01
and in my practice
51:02
I actually very heavily use this test
51:04
and actually to assess how well
51:06
for example
51:07
is Hepzato or any of the liver directed therapies
51:10
or even systemic therapy
51:11
is actually working against the cancer
51:14
and so you know
51:14
we've actually had a couple of
51:16
several patients at our institution
51:17
where we've actually been trending
51:19
DNA levels over time
51:21
and I would say about five of our patients
51:22
where we've actually been monitoring it
51:24
have actually been able to clearly demonstrate
51:27
their CT
51:27
DNA going from detectable at the start of treatment
51:30
all the way down to undetectable
51:33
so this is still an area of evolving research
51:35
and you know
51:35
what does it mean to have an undetectable level
51:38
could that level then come back
51:40
you know
51:40
this is an area that we still need more patients to
51:43
accrue to better learn from
51:44
so we can decide
51:45
does it make sense to also monitor patients with CT
51:48
DNA while on therapy
51:50
and I think we need a standard CT DNA test as well
51:53
right so
51:54
the CT DNA stuff really came out of the Kimmtrak trial
51:57
but the assey or the test they used for that trial
52:00
isn't actually commercially available
52:01
was done designed specifically for that
52:03
study and in that study you know
52:06
I think it was 20 to 30% of patients who
52:08
had metastatic disease to the liver
52:10
they couldn't actually detect CT DNA
52:13
so there
52:13
are some other clinically
52:14
available tests that are approved
52:15
for any immuno therapies that we can use
52:18
and I definitely try using them
52:19
but I think we're still learning a lot
52:21
for people who we can detect to see CT DNA
52:23
and it correlates really well
52:24
super helpful
52:26
or patients who their number is incredibly low
52:29
can't really trust what the changes are
52:30
cause the changes are too little
52:32
for people who it's negative
52:34
so it's a great tool if it works
52:36
but for those who doesn't work for
52:38
I think it's still we're still learning yeah
52:40
uh you know
52:41
for someone who had an isolated liver lesion
52:44
that's been stable on Kimmtrak
52:45
if we knew their CT DNA was positive
52:47
and is now negative
52:50
this is a super gray area
52:52
but I would very
52:53
be very comfortable trying doing Histotripsy
52:56
or an ablation or resection
52:58
or some sort of local therapy
53:00
because one of
53:00
the things we always have to balance is treating
53:03
the cancer but also maintaining a high quality of life
53:08
and Kimmtrak can work great
53:10
but it is also weekly treatment
53:12
and being tethered to a clinic once every week
53:15
for two years can take a real big toll on patients
53:18
and so you know
53:20
we don't know if stopping Kimmtrak in the
53:22
situation would be helpful or not
53:24
or be safe or not
53:26
but I think it's a reasonable thing to consider
53:28
trying to balance both
53:29
the quality of life of the patient
53:30
while also maintaining cancer control
53:32
it's a difficult situation
53:34
it's one of these things where
53:35
if you talk to three people
53:36
you'll get six answers hmm yeah
53:39
general question and I did kind of type some answers
53:42
you know Doctor Burns has been in the back end
53:43
typing a few answers to questions as well Histotripsy
53:46
Hepzato Kit insurance coverage
53:48
pretty sure Doctor Moser Doctor Ma you guys
53:51
you guys could weigh in on this
53:52
but I'm pretty sure from talking to the people I know
53:55
through the Delcath Systems group
53:57
that they have insurance codes
53:59
like pretty well pretty well across the board
54:00
they're pretty well easily covering Hepzato right
54:03
I've had no issues okay
54:06
we have it's since it's FDA
54:08
approved and approved by Medicare to my knowledge
54:10
all private I live in Los Angeles
54:13
so of course okay
54:14
wherever you live in the audience
54:15
it's gonna be a little bit different
54:17
but pretty much every major insurance carrier
54:20
provides coverage for Hepzato
54:21
specifically for metastatic uveal melanoma
54:23
keep in mind the device was developed for this
54:25
if you have colon cancer that's metasized
54:28
its way off limits so we have not had any barriers and
54:32
we started as soon as it was commercially available
54:35
yeah it's the same here in the Midwest from Wisconsin
54:38
there haven't been any actual
54:40
issues with getting the approval
54:41
just because it is an FDA approved treatment
54:44
but I would say the biggest challenge
54:45
I would say is really getting the
54:47
insurance coverage of the growth factor
54:49
I think that's been the biggest hurdle for me
54:51
often times because
54:52
it's really dependent on whether
54:54
you do something that's in clinic
54:55
versus
54:56
the growth factor that you can actually take home
54:58
so that's been actually the biggest barrier for me
55:01
not necessarily the Hepzato Kit
55:03
okay
55:04
I don't have Doctor Burns on here
55:06
but he was starting to type an answer
55:08
so I'm like
55:08
trying to look and see if he got his answer typed
55:11
I'm at the bottom here is insurance...
55:14
so Doctor Burn says Medicare is covering
55:17
some commercial plans are covering
55:19
but there is a lot of denials coming from
55:21
commercial insurance
55:22
so it's one of those kind of frustrating patterns
55:24
and I think that Kimmtrak experience this as well
55:26
is that and after initial approval
55:28
there was a period of time when
55:30
kind of private insurance
55:31
commercial insurance
55:32
had a little bit more to say about not covering it
55:35
versus once Medicare Medicaid got on board
55:37
and then it became a little bit of an easier process
55:41
at least from talking to a lot of insurance people
55:42
like in my personal story
55:45
that's what I've learned is that it is a process
55:47
and that depending on the therapy
55:49
depending on the approval codes
55:50
and all of the different
55:51
the data that they have at the moment
55:53
it can
55:54
take some time to get that kind of blanket approval
55:57
for all insurances
55:58
and that even if you have that
55:59
you might still run into it with stuff
56:01
years down the road because somebody's
56:03
you know computer acted up in the insurance coding
56:07
and I think just to be
56:08
try to be as unbiased and fair as possible
56:11
I one of the challenges
56:11
Doctor Moser mentioned earlier
56:14
in the conversation is that
56:15
you know the Histotripsy
56:17
he's not specifically designed for uveal
56:19
melanoma specific wasn't FDA authorized for that
56:22
and the published data so far
56:24
if you do a Google search and so on
56:26
it's not designed for
56:27
uveal melanoma and did not look at long term results
56:29
so I think hopefully if that data comes
56:32
then insurance companies will play ball a little bit
56:36
but it's right now my guess is
56:38
it's a little bit challenging
56:39
because an insurance providers gonna say well
56:42
show us the data right
56:43
because that's how they they work
56:45
and I don't know if Doctor Ma
56:47
Doctor Moser agree with that or not
56:49
I 100% agree and I think that's
56:51
why it's important to participate in these registries
56:53
and stuff that Doctor Burns talked about because
56:56
you know to get insurances to pay stuff they like data
57:00
but the other thing they like is guideline approvals
57:03
right so even if it's not FDA approved
57:06
if we can generate enough data saying hey
57:08
this works in uveal melanoma
57:11
petition the NCCN guideline
57:12
uveal melanoma committee to say yes
57:15
we think there's enough data to support this
57:18
if an NCCN guideline says yes
57:21
we think this is useful
57:22
it's really hard for insurance to say no
57:24
but NCCN is data driven so participate
57:28
so if you're someone who's gotten histo
57:30
participate in these databases and all of these things
57:32
cause
57:33
that's gonna make it easier for people in the future
57:35
to get it if the data is as exciting as we think it is
57:38
right
57:38
I think have that Histo is gonna be great option
57:40
we just need the data to prove it
57:42
so we can get it on the guidelines and use it more
57:45
yeah and you guys
57:46
I apologize we lost Doctor Burns
57:47
because his internet cut out suddenly
57:49
and he's been trying to get back on
57:50
on his phone
57:52
but I appreciate you guys jumping in
57:53
and kind of weighing in for Histo
57:54
so in you know
57:55
in his absence and talking about getting back
57:57
you know
57:57
getting to those registries that applies to all of us
58:00
right and for all areas of our disease management
58:03
like make sure that you are participating in
58:05
the patient led registry so
58:06
we've got the Insight Registry led by A Cure In Sight
58:09
there's other registries
58:10
led by other organizations that are tracking
58:12
patient driven like natural history data
58:14
but then we also have oncology data driven
58:17
registries like the one that Doctor Burns is doing
58:19
and I'm sure that there's something
58:20
very specific to Hepzato Kit
58:22
where you're gathering data as doctors
58:24
collectively around the country
58:26
to just know what's happening
58:27
what are the best practices
58:29
and the evolution that needs to happen over time
58:32
speaking of kind of the where's it going from here
58:35
we have people from Canada
58:36
we've got people from the UK
58:38
we've got people in Asia who are just like
58:40
well when is this coming to me
58:41
do we have any indication of like
58:43
Hepzato making it to Canada
58:44
I feel like that's my first question
58:46
anybody know anything about that
58:48
Danet I don't know about Canada
58:49
it is available in Europe
58:51
okay actually has been available in Europe
58:53
it goes by different name there
58:54
it's called Chemo Sat
58:56
and it's been available in Europe prior to the US
59:00
to my knowledge it's not yet available in Canada
59:02
and I don't know the status
59:04
and I think there was a Q&A about
59:06
anywhere in Asia and to my knowledge
59:08
it's not available in Asia commercially
59:11
I don't know if there are plans to do that
59:14
the device is made by effectively
59:17
like a kind of a very relatively small company
59:19
so you know
59:21
you can imagine
59:21
it's not like these guys have a ton of resources
59:24
to kind of do a immediate worldwide expansion yeah
59:28
that makes sense
59:29
it is taking time in all of these aspects
59:31
do we have patients like internationally
59:33
are they able to travel to centers here in the US
59:36
if they wanted to have Histotypsy or Hepzato Kit done
59:39
and they came from you know
59:41
I don't know Italy or just somewhere random
59:45
is that a possibility
59:46
do we have centers that accept international patients
59:48
or is it kind of across the board
59:50
yeah it's gonna be across the board
59:53
I think the one or two challenges as
59:55
so
59:56
I think Histotripsy is probably more feasible to get
59:59
for an international patient
1:00:02
the Hepzato Kit tends to be more expensive
1:00:05
and so
1:00:06
we have had people from outside the United States
1:00:08
inquire
1:00:10
the price tag which is not the physician price tag
1:00:12
it's the hospital price tag
1:00:15
tends to be very high
1:00:17
and unfortunately for an international patient
1:00:19
our hands are a little bit tied I don't
1:00:21
I as a physician
1:00:23
who works in a very large institution
1:00:24
with tens of thousands of people
1:00:26
I have zero control over that I have no say
1:00:29
they don't care what I have to say about the pricing
1:00:31
so I don't see the bills
1:00:33
which is actually great for me
1:00:34
because I don't have to worry about that stuff
1:00:36
and so that unfortunately
1:00:38
acts as a deterrent
1:00:39
to get Hepzato in the United States
1:00:41
for foreigner so I would encourage you
1:00:42
if you are interested
1:00:44
and you don't live in the United States
1:00:45
contact a European site
1:00:47
they are gonna be much more in my personal opinion
1:00:50
more cost reasonable
1:00:53
compared to any American site for Hepzato at least
1:00:56
I agree I think if you're an international patient
1:00:59
doing something
1:01:00
that doesn't have a direct per patient cost right
1:01:04
so with Histotripsy a hospital buys a machine
1:01:06
they've already paid that cost
1:01:08
so the cost that they would have to bill
1:01:10
for the patient is a little more flexible
1:01:13
whenever you have a drug
1:01:14
the hospital has to purchase the drug like Hepzato
1:01:18
and then purchase it for that specific patient
1:01:20
that's not a cost the hospital can control
1:01:23
and most hospitals can't
1:01:25
just write off the amount that these drugs cost
1:01:28
and so
1:01:28
I think for someone trying to pay cash for Hepzato
1:01:31
it's expensive even if
1:01:32
the hospital is willing to do it for nearly free
1:01:35
because with the hospital still has to buy the chemo
1:01:38
which has to be passed to the patient
1:01:39
so I agree
1:01:40
I think doing something that doesn't require a drug
1:01:42
like Histo is far more reasonable
1:01:44
unless you have substantial financial means
1:01:48
yeah I agree
1:01:50
I guess the only final thought I have to say is
1:01:52
you know for patients who are very interested in
1:01:54
sort of these newer and novel therapies
1:01:56
you know for example
1:01:57
I mean for those international patients you know
1:02:01
it's not unreasonable to think about
1:02:02
you know participating in clinical trials
1:02:04
you know as
1:02:04
you know
1:02:06
all the drugs we have nowadays
1:02:07
had to go through clinical trials in order
1:02:09
to get to that FDA approval
1:02:11
and to some extent
1:02:12
some of these trials and drug therapies
1:02:14
are covered by the sponsors
1:02:15
and so you know
1:02:16
Delcath
1:02:17
sort of being the sponsor or the makers of Hepzato Kit
1:02:20
they
1:02:21
actually had this available in
1:02:22
Europe for quite some time
1:02:23
before it came to the US
1:02:25
and so you know
1:02:26
it's my understanding that
1:02:27
you know a lot of these
1:02:28
Hepzato based studies might actually
1:02:30
potentially be available in Europe
1:02:31
so I would encourage you know
1:02:33
for patients who are international
1:02:35
if they're thinking about
1:02:36
you know some sort of liver directed therapy involving
1:02:38
you know Melphalan liver directed therapy
1:02:40
maybe at least consider it
1:02:41
sort of exploring clinical trials as an option
1:02:45
okay
1:02:45
I do want to end on this note around clinical trials
1:02:49
this is just kind of a
1:02:50
I don't want to spend a ton of time on this
1:02:52
but I do want this discussion
1:02:53
kind of just opened up a bit
1:02:55
for patients who have questions about
1:02:57
you know if I choose to use Hepzato Kit as
1:03:00
you know a front line treatment or first line treatment
1:03:03
or if I have a Histotripsy treatment
1:03:05
because I'm one of those rare patients
1:03:07
who maybe only has one liver tumor
1:03:08
and it stays that way
1:03:09
despite all of the indication that it should change
1:03:12
does this change
1:03:14
how a patient can then participate in clinical trials
1:03:17
I guess this is maybe a Doctor Moser question
1:03:19
that's why I was trying to tap into the
1:03:21
one of the questions in the chat
1:03:22
so right now yes
1:03:24
for some so you know the major randomized
1:03:28
trials right now in the United States for uveal
1:03:30
melanoma are the Ideaya study
1:03:31
the Replimune study
1:03:33
both of them do exclude prior liver directed therapies
1:03:36
be it radiation ablation Hepzato Histo etc
1:03:41
one of them
1:03:42
maybe both of them do allow prior metastectomy
1:03:46
which means you'd cut out just one or two tumors
1:03:49
I don't know that for sure
1:03:50
I think one of them does the other one I don't
1:03:52
so if you do that
1:03:53
you would lose the opportunity to go on
1:03:55
those two studies now
1:03:56
there is a new randomized study that's coming to the US
1:04:00
we're hoping
1:04:01
this will be here in the next couple of months
1:04:03
and that is a randomized study from an Ionctura
1:04:05
using a drug called Roginolisib
1:04:08
and that randomized study should not exclude you
1:04:12
or it
1:04:13
should not exclude patients who've had local therapy
1:04:16
such as this so there are options coming
1:04:18
but the two most readily available
1:04:20
randomized studies for uveal melanoma
1:04:22
do exclude patients who gotten local therapies
1:04:24
at this time my recommendation for patients is
1:04:28
talk to your medical oncologist
1:04:30
and find out and if your medical and I
1:04:33
this is gonna maybe raise some eyebrows
1:04:35
if your medical oncologist does not
1:04:37
see a good amount of uveal
1:04:38
melanoma patients
1:04:39
I don't find these two guys on the bottom and fly to
1:04:42
you know Wisconsin or Arizona or somewhere shop around yeah
1:04:45
I mean this is one where you don't wanna
1:04:48
you don't wanna jail yourself right
1:04:50
like some of these trials are really promising
1:04:52
and if they exclude
1:04:54
Histotripsy or Hepzato
1:04:55
and you come to me and you get Hepzato and
1:04:59
I actually ask every patient like
1:05:00
have you talked to a uveal melanoma oncologist
1:05:02
and I'll even email our guy
1:05:03
even if he's not seeing them
1:05:05
would this patient be a candidate
1:05:06
for the first line trials
1:05:08
that Doctor Mosers talking about
1:05:09
because I don't wanna
1:05:10
I don't wanna jail someone's downstream options
1:05:13
right so
1:05:15
and you know as we all know
1:05:16
everybody on the webinar right now
1:05:18
all the participants uveal
1:05:20
melanoma is something that no one's ever heard of
1:05:22
unless you have uveal melanoma right
1:05:25
so even medical oncologist correct me if I'm wrong guys
1:05:29
90% of medical oncologists never see
1:05:31
uveal melanoma patient right
1:05:32
so it's not their fault
1:05:33
it's just they don't get exposure to it
1:05:36
hmm yeah it's a rare disease
1:05:38
and I think Danet you bring up an interesting point is
1:05:41
you know sort of how do we decide on sequencing right
1:05:43
do I first maybe consider a clinical trial first
1:05:46
or maybe think about Hepzato first right
1:05:48
I mean I would always say
1:05:50
you know public service announcement
1:05:51
I would say for a rare cancer like this
1:05:54
you know the only way we're gonna get better therapies
1:05:56
is a patient actually participate in clinical trials
1:05:59
you know there's a lot of misunderstandings about
1:06:01
how clinical trials operate
1:06:02
but I think
1:06:03
it's important for patients to
1:06:04
just talk to their oncologist
1:06:05
learn more about it
1:06:06
better understand what thier options are
1:06:09
but you know
1:06:09
the thing I have to say about like Hepzato
1:06:11
for example is
1:06:12
you know you have to have liver only disease
1:06:15
and if you have disease outside of liver
1:06:16
they have to be definitively treated
1:06:19
the concern that I often bring up with patients
1:06:21
and this is a discussion I have
1:06:22
when we discuss risk benefits
1:06:23
whether it's you know
1:06:24
clinical trial other therapies
1:06:26
Hepzato other liver directed therapies
1:06:28
is if you precedingly receive a different therapy that
1:06:32
you know does well
1:06:33
but then unfortunately the disease worsens
1:06:35
or metastasizes out outside the liver
1:06:38
and Hepzato may no longer be an option
1:06:40
and so those are the conversations I have with patients
1:06:43
and you know
1:06:44
when it comes to clinical trials
1:06:45
you know they can be optimized
1:06:46
labor intensive
1:06:47
and you have to think about the quality of life
1:06:49
for patients how often they have to come into visits
1:06:52
you know for the treatment monitoring
1:06:53
and so
1:06:53
those are some of the aspects and components I often
1:06:56
frequently discuss as well
1:06:57
and not every center has clinical trials available
1:07:00
so on some occasions
1:07:01
patients may even need to travel as well
1:07:04
pretty far for them
1:07:06
that's such a good point
1:07:08
Doctor Moser do you have anything you wanna add there
1:07:10
no I agree
1:07:10
and you know like Dr Ma said
1:07:11
not only is it spreading outside of the liver
1:07:14
but right now the FDA labels for Hepzato says
1:07:17
less than 50% liver involvement
1:07:19
now I think we're learning that maybe
1:07:22
that may not be the case
1:07:23
we may be able to safely do this that's still unknown
1:07:26
so if someone has you know had 40% of their liver
1:07:30
you know you you have to just watch it closely
1:07:32
you know and I put people on frontline
1:07:34
uveal melanoma clinical trials
1:07:36
but also told them
1:07:36
we're gonna watch your labs like a hawk
1:07:38
if your LDH goes up
1:07:39
or your liver enzymes change or anything
1:07:42
we're gonna scan you early
1:07:44
so we can transition quickly to something like Hepzato
1:07:47
so we don't lose that window
1:07:49
you know yeah
1:07:49
and I'm in agreement with that 50% mark guys
1:07:53
I mean it's
1:07:54
I think the risk is that sometimes these MRI and CTs
1:07:58
they're imperfect tools right
1:08:00
so the risk is that let's say the MRI CT says you have
1:08:04
you know the radiologist reading well
1:08:06
you have a 60 70% replacement of your liver with tumor
1:08:10
and then when we do the angiogram
1:08:12
we see it's really not 67% it's really 99% right
1:08:15
and that's the risk and then it's you know
1:08:18
doing this stuff is not gonna work
1:08:19
and so we've been we've tried to do our best
1:08:23
in kind of abiding by that rule
1:08:26
I do I get concerned
1:08:27
when they have a very heavy tumor burden
1:08:29
and I don't know this is the best option for them
1:08:33
yeah and I will just
1:08:35
because I've heard Doctor Burns talk about this before
1:08:37
in just generally around liver tumors
1:08:39
this is where if the liver burden is really high
1:08:42
he and his team and they know the Histosonics
1:08:44
they're evaluating
1:08:45
you know how often can we go in with someone who has
1:08:48
basically nothing left and use Histotripsy as kind of a
1:08:52
our last option
1:08:53
to just try to give some relief to the liver
1:08:56
and they're seeing that you know
1:08:57
in some cases that can be helpful it's just you know
1:09:00
of course the data is still evolving obviously
1:09:02
uveal melanoma we're still learning
1:09:05
but I
1:09:06
I appreciate you guys for like just talking about this
1:09:08
because I think that this is something we need to know
1:09:10
about us patients
1:09:10
like you said Doctor Padia
1:09:12
like we shouldn't be going into a treatment
1:09:13
expecting
1:09:14
to then be able to jump right to a clinical trial
1:09:17
and I think the other maybe caveat that
1:09:19
I wanna add to this
1:09:20
because this can make it sound a little grim
1:09:21
if you're feeling like oh
1:09:22
well what if I can't get in a clinical trial
1:09:25
because none of them have openings right now near me
1:09:27
because there are limited slots in some cases for
1:09:30
you know certain trials
1:09:31
so just limitations to the trial being open
1:09:34
or the accessibility of the trial
1:09:36
or maybe you're just not a patient who
1:09:38
presents with disease in a way that it would be
1:09:40
effective to be part of a clinical trial
1:09:42
I know I was one of those people
1:09:43
I had one spot and it just stayed one spot
1:09:46
and then we treated it
1:09:47
and I had nothing show up for like 15 months
1:09:49
that's not normal like most people aren't like me
1:09:52
and so I just was a little bit discouraged
1:09:54
I think as a patient to find out like
1:09:56
oh like I thought that I could do clinical trials
1:09:58
oh never mind this
1:09:59
this one microwave ablation I had almost two years ago
1:10:02
that was the one
1:10:03
that initially kind of disqualifies me
1:10:05
from most of those ones that say
1:10:07
you can't have liver directed therapies first
1:10:09
so and doctor Moser gave me some hope
1:10:11
so I wanna like
1:10:12
give patients some hope
1:10:13
that if you choose to do spot treatment
1:10:15
or you choose to do Hepzato first
1:10:16
and have some kind of a liver or directed therapy
1:10:19
and then you need something else
1:10:20
are there avenues
1:10:22
of compassionate use or expanded access for patients
1:10:25
and how do you kind of figure out that path
1:10:28
there can be it's a case by case basis
1:10:30
but also
1:10:31
if you get a liver directed therapy and you get
1:10:34
you know two years or a year
1:10:37
we're constantly changing
1:10:38
new trials are constantly opening up right
1:10:40
we had discussions at the big
1:10:42
Ocular Oncology Cooperative Group last month about a new
1:10:46
trial that could be coming to uveal melanoma this year
1:10:48
and so it's never wrong to say
1:10:50
I'm gonna do the liver directed therapy
1:10:52
because options are changing
1:10:54
and I think that's why
1:10:56
it's important to remember what Doctor Padia said
1:10:58
which is
1:10:58
connect with someone who knows you uveal melanoma
1:11:01
even if you see them kind of once a year or one
1:11:04
every other visit to quarterback your care
1:11:06
you know we know what's coming
1:11:08
it can help direct you there
1:11:10
and we can also let you know what trials are available
1:11:13
because there are some you know
1:11:14
earlier phase uveal
1:11:15
melanoma specific trials
1:11:17
that don't exclude you from prior directed therapy
1:11:19
you may have to travel and that may be a discussion
1:11:21
but there are a lot of options out there
1:11:23
and it's constantly changing
1:11:24
so yeah
1:11:26
now the treatment space is definitely changing a lot
1:11:28
frequently I really
1:11:30
I'm very excited to talk about this
1:11:31
COOG meeting that just happened
1:11:33
kind of happened when I was in recovery
1:11:34
and it was great so you guys
1:11:36
there's so many good things on the horizon
1:11:38
I hope that those of you listening
1:11:39
you've had a lot of good information
1:11:42
you've taken away maybe some new information
1:11:44
maybe some misconceptions about
1:11:46
either of these therapies have been
1:11:49
fixed or like you've you know
1:11:50
gotten better information around them
1:11:52
but thank you guys for your participation
1:11:54
this has been one of the highest participated in
1:11:55
webinars that we've had with just countless questions
1:11:58
and I'm really grateful to all of you for being here
1:12:01
listening and staying with us
1:12:02
and of course to our doctors
1:12:03
Doctor Padia Doctor Burns
1:12:05
Doctor Moser and Doctor Ma
1:12:06
thank you guys so much for your time
1:12:09
if anyone wants more information
1:12:10
specifically on Hepzato Kit
1:12:12
I did post this on the webinar page
1:12:15
that you can go to the Hepzato Kit website
1:12:17
I believe it's HepzatoKit.com
1:12:19
you can also reach out to
1:12:21
I believe they have a map on there
1:12:22
where you can find
1:12:23
centers that are offering Hepzato Kit
1:12:25
near you you can of course also reach out to these
1:12:28
these doctors as well
1:12:30
and find out if they can refer you to somewhere
1:12:32
maybe closer if you're looking to
1:12:33
need to travel to find Hapzato Kit
1:12:35
same with Histotripsy
1:12:36
Doctor Burns said to go ahead and
1:12:39
and share that
1:12:39
if you are interested directly in working with him
1:12:42
you can reach out at Histotripsy@Providence.org
1:12:46
that's their main Histotripsy coordinating email
1:12:49
you can also go to the Histosonics website
1:12:51
and they too will have a team of people
1:12:53
who will direct
1:12:54
you to the centers that are closest to you
1:12:55
because there are
1:12:56
rapidly expanding places that are getting the
1:12:59
Histotripsy machine
1:13:01
I know of people on the East Coast
1:13:04
not gonna say names
1:13:05
but in a very well known East Coast hospital
1:13:08
they're getting the Histotripsy technology
1:13:10
it's already here in Arizona
1:13:11
so it is expanding and you know
1:13:13
like that like Hepzato Kit
1:13:15
like the access to it is growing
1:13:16
so I love that we have these to use
1:13:19
and I just want to thank you guys again
1:13:20
for being part of this webinar
1:13:22
thanks for inviting me with this was super fun
1:13:24
hopefully people found it informative and helpful
1:13:26
thanks everyone
1:13:28
thank you yeah and Doctor Brown says sorry
1:13:31
he just we we tried to get him back on
1:13:32
and the internet didn't wanna cooperate so
1:13:35
but thank you guys
1:13:36
and if we have any other questions that come in
1:13:38
I will make sure to reach out to these doctors
1:13:39
and just get some better answers
1:13:41
if I can but in that
1:13:42
with that I'll go ahead and dismiss our panelists
1:13:44
and we will head to the rest of our days
1:13:47
this is being recorded
1:13:48
so those of you who want to catch the recording later
1:13:50
rewatch it for your
1:13:51
of your own purposes or to share it with a friend
1:13:53
please
1:13:54
make sure to look for this on our YouTube channel
1:13:55
and subscribe and on our podcast
1:13:57
where you can listen to it as well
1:13:58
but this is definitely like a listen on YouTube
1:14:00
cause you wanna like see the visuals
1:14:02
so we will see you guys later
1:14:04
have a good wonderful weekend