Locoregional Therapies for Liver Tumors: 2021 Update

March 01, 2021

Information

Liver CME Symposium | February 25, 2021

David Madoff, MD

ID6237

To CiteDCA Citation Guide

00:00OK, welcome to the second episode of
00:05our yearly after my lecture series.
00:11Today we are going to have
00:16our cheaper international.
00:18An ideology, namely.
00:22Doctor Madoff, David Madoff, David Madoff.
00:28Did his Bachelor degree and Emory University,
00:31and then the MD and University speech book
00:35from there went to SUNY for the residency?
00:38It was Othello, and then a faculty
00:42member at MD Anderson.
00:44From MDN, Nasoni moved to we Cornell
00:47Presbyterian in New York City,
00:49where he became the section chief
00:53of Interventional Radiology there
00:56and join him in July 2019 is now.
00:59Professional radiology and
01:01medical oncology section,
01:02chief of interventional radiology and
01:04vice chair for visas in the Department
01:08or radiology and biomedical imaging.
01:11David is a great aspect in liver tumor
01:14treatment without correctional treatment,
01:15and if you look at his CV and
01:18his publication, he has been.
01:22One of the forces behind the
01:26great developments that.
01:28I've been brought by interventional
01:31radiology in the treatment of liver cancer,
01:35and he in particular is very interested
01:38in all the method to which we can increase
01:43liver regeneration before and after
01:46surgery on Echologics surgery to deliver.
01:50David.
01:53Is one of the members of our team
01:56are as as highlighted in this slide.
02:01The treatment of Reperta
02:03circus numbers very complex.
02:06We have Transformers, action ablation,
02:09radiation, systemic therapy.
02:11We need to mind also the liver
02:15disease that is present in all if not.
02:20Most if not all,
02:21the patient liver cancer,
02:23and so it really takes a village
02:25to be able to manage and treat this
02:28patient and it is very important
02:31concept that this patient should
02:33be treated in referral centers.
02:35Yeah, you can see some of our members.
02:38Actually there should be 2 times than
02:41the pictures that are shown here,
02:44but I don't want to take more time to our.
02:50Lecture tonight then,
02:51so I'll stop here and I like
02:53the baby in the beginning.
03:02Jay Silva I assume you can see my screen.
03:06Yep. OK, so thanks Mario for
03:10that really nice introduction.
03:12What we're going to talk about today is
03:15local regional therapies for liver tumors.
03:19A 2021 update. What I wanted to do
03:22is really go through a whirlwind tour
03:26of what IR or IO can actually offer.
03:30And not necessarily bore a lot of the
03:34audience with a lot of really hardcore data,
03:37which I definitely have, but I think to
03:39make it more interesting and palatable,
03:42I think that we're going to show
03:45a lot of cases and make this.
03:47I think, quite interesting.
03:50So these are my disclosures.
03:53Some of which I'm going to
03:55be speaking about today. So.
03:58As you all know.
04:01Interventional radiology is involved
04:03in numerous types of tumors, right?
04:06We treat both primary liver cancer
04:10and metastatic liver cancer for
04:13the purpose of this talk today
04:15to focus primarily on each CC,
04:18with the understanding that a
04:21lot of the local local regional
04:24therapies that we can offer.
04:28Actually can be translated
04:31into other disease types.
04:34So when talking about the goals of therapy,
04:36there are really 3.
04:38There is what you would call curative
04:40therapy and that could be, you know,
04:43transplantation resection and
04:45ablation for early stage disease.
04:47We also I guess you briefly mentioned my
04:50area of interest in liver regeneration.
04:53We can convert patients who are
04:55unresectable to resectable,
04:56and that can typically be done by portal,
05:00vein, embolization, radiation, lobectomy,
05:01and transarterial emblow therapy,
05:03which we'll get into later.
05:05And for those patients that are
05:08of intermediate and advanced age,
05:10we really can offer what's called palliation.
05:12Which is, you know,
05:14can be transarterial embolization
05:16and or ablation.
05:17So all of the different types of
05:20therapies that we offer really
05:22depends on patients tumor Histology,
05:24the number and location of the
05:26tumors within the liver,
05:28the extent of the underlying
05:30liver disease and of course,
05:32the presence or absence of
05:35extrahepatic disease.
05:36Now what I want to do first was
05:38getting to the whole idea of defining
05:41the different types of procedures.
05:43It turns out that a lot of practitioners,
05:46yet a lot of the time you get a
05:48lot of the types of procedures
05:51that we do kind of misinterpreted,
05:54meaning that the terminology is often
05:56used entertained interchangeably,
05:57and when you go to tumor boards or you
06:00listen to or you read your image Ng,
06:03even your image, even your image Ng.
06:06Reports.
06:08Taste, for example,
06:09is sometimes used in the place of
06:11taec or transarterial embolization,
06:13you know.
06:14See, taste is sometimes used
06:16for debt ace and vice versa.
06:18When we talk about microwave ablation
06:20as well as you'll hear later,
06:22it's always called RFA,
06:25even if it's not really.
06:27Medium embolization is sometimes
06:29referred to as radiation therapy,
06:31and in addition you know when
06:33I'm reading these reports.
06:34There's often times where will do an
06:37embolization where we're discussing,
06:39you know,
06:39an ablation cavity,
06:41and this really isn't the case
06:43and the reason why
06:44I'm saying this and the reason why it's
06:47so important is that it really has
06:50major implications for patient care.
06:52Medical record keeping and billing,
06:54so I see a lot of times where a patient may.
06:58Get a treatment for an image in finding and
07:01in fact it may actually not be necessary
07:04and I'll get into an example of that later.
07:08Of course, before we can even talk
07:11about treatment, I want to stress the
07:14importance of percutaneous biopsy.
07:16OK now, interventional radiologists often
07:19think of this as kind of a mundane procedure.
07:23It's kind of basic and.
07:26In my opinion, Proteinous biopsy is
07:28probably one of the most important
07:30and impactful procedures that we do.
07:33This is a case that I want to show
07:36which is a 64 year old female with
07:39squamous cell cancer of the tongue
07:41base who has a pet CT positive avid
07:44lesion in the left lobe of the liver
07:46and of course because of the location
07:49because of the disease,
07:51it's very important to get a diagnosis now.
07:54We would all agree that this lesion.
07:56It's probably very difficult to biopsy.
07:59OK, it's at the very edge of the
08:01liver is literally right under
08:03the pericardium and diaphragm,
08:05and there really is no correlation
08:07with imaging findings.
08:08But you know,
08:09we we were able to do the biopsy
08:12as you see here,
08:14and this is actually the bottom of the heart.
08:17OK,
08:18and in fact the patient did not have
08:20squamous cell carcinoma but actually
08:22had low grade B cell lymphoma,
08:25which completely changed the patients.
08:27Management.
08:27So the reason why I bring this up is that.
08:32These procedures that you see
08:33here can be very, very difficult.
08:35OK from a technical perspective,
08:37but I think that it would be very
08:40important for the referring physicians
08:42to actually reach out to one of us in IR
08:46to see if it's actually feasible or not.
08:48And in this case,
08:50I think it really helped the patients.
08:53No diagnosis and therefore prognosis.
08:56So just to talk about HCC a little bit,
09:00we're all aware of the Barcelona
09:03Clinic liver Cancer Staging system.
09:05As you know,
09:06we see patients all the range from
09:09very early stage or stage zero to
09:11terminal stage or stage D and the
09:15treatments obviously fit into where
09:17patients fall on this staging system.
09:20So typically patients that are
09:22very early stage or early stage
09:24have very limited disease,
09:26are often considered.
09:27Or ablation resection or transplant
09:30and depending on where they fall into this,
09:33that will determine the outcome of what kind
09:36of procedures that you would actually do.
09:39Intermediate stage is what we typically
09:41do for local for regional therapy,
09:44or maybe chemoembolization
09:45or radio embolization,
09:47which will get into and then systemic therapy
09:50and basic supportive care are released.
09:53It reserved for the more advanced
09:55age is the reason why I put the.
09:59Question mark for survival.
10:01Is that we go through the gamut of.
10:04Procedures that we can offer
10:06and then at the end
10:08of the talk, we're actually going to fill in
10:11where the survival actually is at this time.
10:14So there are multiple treatment
10:16options for Liberty Mears for surgery.
10:18We obviously have transplant or
10:20hepat ectomy and we if the patient
10:22has two small liver remnants,
10:24we can optimize the future liver remnant
10:27or FLR with a PV or something else.
10:29Portal animalization we can talk
10:31about a blade of techniques which are
10:34divided into thermal and non thermal.
10:36And for those that are thermal,
10:38we can look at those that are heat
10:41based in those that are cold based.
10:43And then there's a whole host of
10:46transarterial therapies we can offer,
10:47including chemo,
10:48infusion embolization,
10:49chemoembolization,
10:49as well as radio embolization.
10:52So just to bring up local
10:55oblated therapies first.
10:57The goal here is to percutaneously eradicate
11:00all viable malignant cells while sparing
11:04as much normal liver tissue as possible.
11:07We can treat tumors with
11:10unfavorable locations or patterns,
11:12patterns of distribution for resection,
11:14or patients that have multiple comorbidities
11:17that probably cannot tolerate resection,
11:20but maybe have resectable disease.
11:23It's these are most often used
11:25in patients that have what we
11:27consider low volume disease.
11:29It can be used for debulking
11:31an nowadays in recent years.
11:33I guess we can also use it to incite
11:36antigen stimulation for immunotherapy,
11:38and these are typically done
11:40as outpatient and repeatable.
11:42So the way we can do tumor treatment with
11:45local oblated therapies is by cooking,
11:48and that's what we would consider
11:50radiofrequency ablation.
11:51We can boil them.
11:53Which would be microwave ablation?
11:55We can freeze them,
11:56which can obviously be cryo ablation
11:58or we can electrocute them and
12:00that would be called irreversible
12:02electroporation and will go into a
12:04little bit more detail in a second.
12:08So this is a case of radiofrequency ablation.
12:12This is a 61 year old female with
12:15colorectal cancer and an isolated
12:17metastatic tumor in segment 6.
12:19Here we see a 2.2 centimeter tumor.
12:23Here there is an axle,
12:25the avid lesion in segment six,
12:27we place the needle proteins ablation,
12:30and here is one year. Follow up OK.
12:35Each major frequency ablation works is
12:37that you have oscillating electrical
12:39currents via electrodes to tumor,
12:41which results in a resistive
12:43heating and tissue hyperthermia.
12:45The tissue nearest the electrode
12:46is heated most effectively,
12:48and the side of toxicity of course
12:50depends on the tissue impedance.
12:52Now one of the reasons why I
12:55bring this up in the setting of
12:57colorectal cancer is with the next
13:00therapy that I'm going to discuss.
13:02Radiofrequency ablation is
13:04becoming less and less performed.
13:06And in fact,
13:07I haven't performed a radiofrequency
13:09ablation since my days at MD Anderson,
13:12now more than 10 years ago in
13:14terms of microwave ablation,
13:16this is a patient 60 year old
13:18female with HPV induced cirrhosis
13:20and a 2 centimeter HCC in segment
13:23seven who was awaiting transplant.
13:26Here we see the lesion here,
13:28which was simply done with microwave
13:30ablation and a 2.7 year follow up.
13:33There's no residual tumor so the
13:36way microwave ablation works.
13:37Is that you can propagate microwave
13:40energy via an electromagnetic field,
13:42and this induces tissue
13:44hyperthermia via dielectric height,
13:45historist hysteresis with that also means
13:48is basically you dehydrogenated the tumor
13:51and actually cause it to rapidly shrink.
13:54This actually is done in a way where you
13:57get higher ablation efficiency because
13:59you can actually get higher tissue
14:02temperatures and therefore you can get
14:05larger ablation zones with shorter times.
14:07And with this kind of treatment,
14:10it readily penetrates through long
14:11or chart issue where RFA is limited
14:14and it's not influenced by heat sink
14:16effects in the same way RFA is.
14:18What that means is that if you
14:20have a tumor that's sitting on a
14:23portal vein or some kind of vessel
14:25that can draw heat away from it.
14:28With microwave ablation,
14:30it's actually less common.
14:33And this is just a study that just
14:35shows that there similar overall
14:38and recurrence free survival when
14:40you compare microwave ablation RFA.
14:42There was no difference in local
14:45tumor progression.
14:46The technical effectiveness as well
14:48as the major complication rates.
14:50So now that we know that RFA is all it
14:54can be used as a first line therapy.
14:57So can microwave ablation.
14:59In terms of cryoablation,
15:02the goal here is to achieve temperatures
15:05less than 190 degrees Celsius.
15:08It results in direct cellular injury,
15:11vascular injury,
15:12and even immunological injury.
15:14What's interesting here is that you
15:17can place multiple simultaneous probes.
15:19You actually get in a natural
15:22anesthetic effect from the ice,
15:24and as you can see from this example.
15:29Here we see the ice ball,
15:31which is easily seen,
15:32so you can actually sculpt the
15:34lesion that you want to treat.
15:37And because of this you actually can
15:40get very predictable and reproducible.
15:42The treatments in terms the
15:46disadvantages because there's so many.
15:49Needle probes are there that are used.
15:52You can have longer procedure times.
15:54There's a theoretical bleeding risk
15:56and you can actually crack the liver,
15:58and patients could actually result
16:00in cryo shock,
16:01which is a form of tumor lysis syndrome.
16:04Now this is 1 case that I got
16:06from a paper from 2007,
16:08and the reason why I'm showing
16:10this like that is that I've never
16:13used cryo ablation in the liver,
16:15so I just want to show you that
16:18the example that we can do it.
16:21It is being used in other
16:23institutions or be it rarely.
16:25And then the last one is
16:27irreversible electroporation,
16:28so irreversible electroporation is
16:30a way that you can alter membrane
16:33ionic potentials and therefore
16:35induce irreversible disruption
16:36of the cell membrane integrity.
16:39The thought here is that this
16:42is a non thermal ablation.
16:44However there are studies now.
16:47They have been published,
16:49which actually does show a
16:51mild thermal component to it.
16:53So here we see a patient with cirrhosis
16:56and had a very challenging tumor where
16:58you see it right here in segment 4B
17:02and it's sitting right on the bile
17:04duct and right near the portal vein so.
17:08So we thought that thermal ablation
17:10with heat may be very difficult and
17:13may result in some kind of injury to
17:16the bile duct or the portal vein.
17:19So here we see the electroporation
17:21needles placed.
17:22Now these need to be very symmetrical
17:24with so that you get very good electrical
17:27potentials across and here we see the
17:30tumor well treated and then at seven
17:33months follow-up there's no tumor at all,
17:35and that's a great result that's exactly.
17:38What we wanted to happen.
17:40In terms of ablation versus surgery
17:42in these early stage patients,
17:44we can see that there's survival and
17:46recurrence recurrence free survival and
17:48overall survival are not statistically
17:50significant in terms of all comers.
17:52However, when looking at
17:54those tumors that are central,
17:55that means that if a patient was to
17:58have a reception of a central tumor,
18:01it would be a very large and
18:03difficult reception that rate
18:05that ablation actually is favored,
18:07and in fact,
18:08when you look at the major complication rate.
18:11The ablation group is statistically
18:13significantly better than the resection.
18:18And then.
18:23Free in terms of overall and disease,
18:25free survival, but it also looks
18:28at the overall quality of Life OK,
18:30So what they found is that there's
18:32really no difference in overall
18:34and disease free survival when
18:36comparing both ablation and surgery.
18:38However, there was a significant difference
18:40in the quality of life scores such that
18:43the surgery does get a little better,
18:46but never to the level of the ablation.
18:48So when we look at a lot of the
18:52interventional procedures that we do.
18:54We're always looking at quality
18:55of life initiatives and then of
18:57course in these particular patients,
18:59again with low volume disease,
19:01we're always looking to treat these
19:03patients as a bridge to transplant.
19:05So this just is a few studies that
19:08just shows how the results of
19:10keeping patients on the transplant
19:12list so they don't drop out.
19:16So in terms of transarterial therapies.
19:20The rationale is that most liver
19:22tumors receive blood supply
19:24largely from hepatic artery,
19:26that these liver tumors are often
19:28hypervascular, especially HCC,
19:29and that this new metastases are less
19:32common than in other epithelial neoplasms.
19:35This has been initiated over 40 years ago.
19:38Some of the techniques we still
19:40use today when I talk to patients
19:43about some of these therapies,
19:46I do tell them that some of this
19:49therapy has been done for decades.
19:51However, it still is not the same therapy
19:54and I'll get into that a little later.
19:56So the goal here is to selectively
19:59and locally deliver these.
20:00Intra arterial therapeutics to the tumor bed
20:03thereby effectively targeting the tumor,
20:06sparing the surrounding hepatic parenchyma
20:08and minimizing complications in toxicities.
20:10But again, as we discussed,
20:12we really need to understand
20:15what the term tases,
20:16because again,
20:17there's a lot of difficulty within the
20:20literature and within just our own tumor
20:24boards and reporting structures that
20:26that seem to use these terms interchangeably.
20:29Now, all utilized selective catheterization
20:31of the paddock artery branches, but.
20:34Once that's done,
20:35the procedures are actually very,
20:37very different.
20:39So what is bland embolization?
20:41Bland embolization is
20:43embolization without chemotherapy,
20:44only using the embolic agent.
20:46The goal here is to completely
20:49occlude the tumor feeding vessels,
20:51which then can cause ischaemia and process.
20:54Now, because of this,
20:56the paint the procedures can
20:58be sometimes quite painful.
21:00So because of the way that we do
21:03it with very small particles,
21:05that actually leads to this kind of pain,
21:08it may have very different effects
21:11on the vasculature.
21:12There's been a lot of extensive research,
21:14but the precise effect on the
21:17tumor cells largely remain unknown,
21:19and because this is done through a scheme,
21:22yeah,
21:22be hypoxic events may actually
21:24cause activation of several genes,
21:26including veg F,
21:27which can then lead to compens,
21:29atory, angiogenesis, and tumor growth so.
21:32Like I said,
21:33the most common techniques that are used
21:35are these very very small particles
21:36which get very distal into the tumor.
21:39They don't actually make
21:40it to the capillary level,
21:41which may be an issue,
21:43but the goal was always really
21:44to get to near stasis or stasis
21:47while preserving flow to the larger
21:49arterial branches.
21:50This is just a case of a 61 year
21:53old female with HCV cirrhosis who
21:55had a 4.8 centimeter HCC.
21:57The goal here was to embolize her
22:00to get her as a bridge to transplant
22:03because she was very close to being
22:05over the five centimeters that would
22:08keep her within the Milan criteria.
22:10We did this very quickly and we
22:13were able to treat this tumor.
22:15As you can see here.
22:18Totally included and then one month
22:21later totally necrotic and now is
22:23at 4 centimeters,
22:24so she ultimately underwent a
22:27transplant that few months after
22:29the embolization.
22:30This is a patient that in a
22:33different location,
22:34probably would have gotten oblated.
22:36So here we see a very small
22:39lesion in segment
22:418. That's a solitaire E lesion that's
22:43very close to a budding the heart.
22:46So I thought that this would be a
22:50very challenging lesion to a blade,
22:52and I opted for embolization.
22:55We see the Hypervascular
22:57territory within the artery here.
23:00At the end of the procedure,
23:01there's no more tumor blush,
23:03and now on the post embolization MRI,
23:05no contrast enhancement is seen.
23:07And this is another case where this
23:10was a patient that was going to
23:12have a combined bland embolization,
23:14followed by portal embolization in order
23:17to increase hypertrophy prior to resection.
23:19So here we see the tumor
23:21we have replaced right?
23:23Hepatic artery from the smam.
23:25The patient was embolized with
23:26100 Micron microspheres and
23:28then a tolling aquatic tumor.
23:30But in this case we actually saw
23:32significant regeneration to the
23:34point where the patient never
23:36actually needed to get there.
23:38Pve and and ultimately underwent
23:40a successful resection,
23:41and this is just some data that I
23:44wanted to to show where we see some,
23:48you know, 33% median survival.
23:5021 months, you know three years.
23:53We also see some patients that
23:55have very good response rates
23:57and reasonable survival rates.
23:59And then when you have post
24:02op recurrence meeting,
24:03survival can be as high as 46 months.
24:08So what is conventional taste or see taste?
24:11So conventional taste is an infusion
24:13of a mixture of chemotherapeutic
24:15agents with iodized oil followed
24:18by embolization with microparticles
24:20and what the oil does act as in
24:22emulsion that functions as a vector.
24:24To carry these cytotoxic toxic
24:26agents to the panic sinusoids
24:28where drugs gradually are released
24:30from this unstable mixture.
24:32So like I said,
24:34these procedures have been done now
24:36for like for more than four decades.
24:39But when I consent or consult patients.
24:42For these procedures,
24:43I tell him that it's not.
24:45You know,
24:46the same.
24:47We don't do it the same way as
24:50we did in 1977,
24:51and based on the global
24:53utilization of this technique,
24:55the Society of Interventional
24:56Radiology has called in the first line
24:59therapy for inoperable HCC patients
25:01with well preserved liver function.
25:03So unfortunately,
25:04at this time conventional taste
25:05is kind of non standardized.
25:07The trend over the years has gone from
25:11whole liver to low bar to selective.
25:14And also from occlusive to not
25:17necessarily occlusive again,
25:18the hypoxic insult may lead to
25:22actually stimulation of growth
25:25factors that may lead to tumor.
25:28To more tumor growth,
25:30there's various chemotherapeutic
25:31regimens and actually in 2019
25:34in the Journal cardiovascular
25:35Interventional Radiology,
25:36there was a global survey which
25:39basically showed that there's lots
25:41of different ways you can do this,
25:44But the most common embolic agents that
25:47we use these days are again our LOPI,
25:50Dolores Idol, PVA gel foam,
25:53and some others.
25:55So this is one of the two landmark
26:00randomized control trials,
26:01first showing the benefit of.
26:05Embolization it's interesting
26:06that the procedure was performed
26:09for 25 years before we actually
26:11were able to show benefit.
26:13This was a study that was
26:15performed from the Barcelona
26:16Cancer Center and it showed largely that it
26:20was working in a select group of patients.
26:23112 out of 903 that had well encapsulated,
26:26smaller sized tumors in patients with good
26:28liver function and good performance status.
26:31So that was one way that we were
26:34able to justify the use of.
26:36Conventional taste and this was another study
26:39that was performed in an Asian population,
26:42mostly with HPV that also had
26:45taste on demand. I'm sorry.
26:47Taste monthly or every two months,
26:49so they had a scheduled time where they
26:52had it and as you can see there is a
26:57statistically significant difference
26:58in taste versus supportive care.
27:01So how does this work?
27:03Well, basically aside,
27:04all Orlopp Idol is a poppy seed oil and
27:08it acts as a drug carrier that seeks out
27:11the tumors and also acts as an embolic agent.
27:15And we know that we can do this with the
27:17understanding that there's very complex
27:20sinusoidal anatomy and such that the
27:23hepatic artery and the portal vein are
27:25actually connected in this time besides.
27:28And the reason why that's important is
27:31that you can get in paddock arterial
27:33and portal venous occlusion such that
27:36the oil ends up in the tumors crosses
27:38from the artery into the portal vein
27:41and then kind of sits there and then
27:43you block up with particles because the
27:46forward flow is the arterial pressure
27:48is still pushing the oil across into
27:51the portal vein so you block it up
27:54with particles to stop that flow.
27:56This is just a case of a.
27:5853 year old man with multifocal
28:00HCC with chronic HCV and elevated
28:03AFP who has multifocal disease.
28:05This large tumor in segments in savings
28:07for taking some eight and four a.
28:10Here we see it on the CAT scan.
28:13Here's the tumor.
28:14The Lipiodol has iodine in it so you
28:17actually can see it on an X Ray and
28:20here you can see after the procedure is
28:23over where the lipiodol is staining.
28:25The reason why I brought up in the beginning.
28:29About the fact that it's really important
28:32to know what that this is lipiodol
28:34is that I had a report recently of a
28:38patient that I treated with this that
28:40kind of called the Lipiodol Council
28:44vacations of uncertain etiology.
28:46A whole plethora of why you know
28:48what what's going on here.
28:50But when we simply just apply it all,
28:52so like I said,
28:54there's arterial portal communication
28:55is very important to understand,
28:57and the more you get into the portal
28:59vein that apply at all in motion,
29:02the better results you actually
29:03get is born out here.
29:05Now we do see in our tumor boards that
29:08sometimes patients do have some portal,
29:10vein, bland thrombus,
29:11and that may be a reason why their
29:14outcomes for at least their tumor.
29:16Is really well because you're actually
29:18doing an arterial importal embolization.
29:20So I want to show a few cases.
29:23This is a patient.
29:24You see the tumor up here
29:27in segment 8. And.
29:30Again, we see the tumor here.
29:32You see, the lipiodol staining the
29:34tumor on the single flora scopic image,
29:37and you can actually see the
29:39portal vein here next to the
29:41tumor as well as down here.
29:43So at the end of the at
29:45the end of the procedure,
29:47we can see that there is a complete filling
29:51of two of tumor with dilipbhai at all.
29:55And then this is the before.
29:58And then this is one month after.
30:01We see a basically a whole.
30:04And ultimately,
30:05the patient had complete necrosis,
30:07an now at nine months.
30:09Follow-up has no residual disease.
30:13So one of the things that I
30:15think is really important and
30:16we can discuss this in all the
30:18different types of embolization.
30:20But because of applied all being
30:22radiopaque we can see I'm using this
30:24opportunity to talk about advanced imaging,
30:27so it's very important to get high
30:29quality imaging during procedures,
30:30which I believe is critical to
30:32optimize tumor targeting and
30:34this can be done with the 3D
30:36angiography combing or cone beam CT,
30:38which is some of what I showed
30:40or combining a multidetector
30:42CT angiography system.
30:44In your interventional suite and we know
30:46that from studies as early as 2007,
30:49of which I was involved in one from
30:52MD Anderson that you do see a lot
30:54of information that is important.
30:57Over standard digital subtraction
30:58angiography and back then,
31:00when we had very poor cone beam CT,
31:03it showed that we were able to impact
31:06the procedure in 19% of the cases.
31:08There's also now new software that
31:10helps precisely identify tumor feeders,
31:12so we're not just relying on
31:15standard DSA alone.
31:16And then we also with the pie at all,
31:19which isn't the same as with
31:21the other kinds of therapies.
31:23We can actually use this to immediately
31:26look at post procedure imaging.
31:28To show the benefit of the of
31:30the tumor targeting as well as
31:32having confirmation that you
31:34effectively treated the tumor.
31:37So here you see a tumor in. I said,
31:41once you fast here, let me go back.
31:47So in this case we have two HCC's in
31:52segments for a in segment 7 and what
31:55I want to show is a tumor sitting.
31:59Here. And here OK.
32:01And when you do the angio it's very
32:03unclear where these tumor feeders are.
32:06So you have one.
32:07It's definitely in the right,
32:09but you have one here,
32:10which is unclear if it's
32:12coming from the left,
32:13so you can so you can do a cone beam
32:15CT from the left and see no tumor
32:18vascularity and then you do it from
32:20the right and we can see a tumor
32:22there and then the tumor there.
32:24And now we know that we're in the right lobe.
32:28So after the procedure is over,
32:30we can see on a plane image
32:33or a flora scopic image.
32:35One tumor treated here one tumor
32:37treated here an on cone beam CT.
32:39You can see tumor here.
32:42In tumor here.
32:43So now we know that it
32:44was effectively treated.
32:48So this is a case that I did just
32:50last week and I thought it would
32:52be interesting to show 74 year old
32:55patient with alcoholic cirrhosis
32:565.8 centimeter HCC in segment 7.
32:59This is the CT scan right here.
33:02This is a previous treatment area.
33:05We did the angiogram.
33:06We see the tumor up here.
33:11We then see I'm selective image here.
33:13So when we do the cone beam CT thinking
33:15that we may have had the whole thing,
33:17we're missing half the tumor.
33:20OK, so we treated the patient.
33:25And we see a basically a Half
33:27Moon where half of it's missing.
33:29So we even got into the other branch.
33:33C. Feeling of the tumor.
33:35And at the end we can see that
33:38the tumor is completely treated
33:40and then on final cone beam CT.
33:44There is complete embolization with lipiodol
33:46so you can see this is very important.
33:50And I just wanted to show that we have
33:52also imaging software that we can use
33:55to track these tumors very nicely.
33:57I don't want to get all details,
33:59but you can see that we have a
34:01road map simply goes straight to
34:03the tumor and that I think results
34:05in a much more effective therapy.
34:07And we published on this back in a 2019.
34:11When we look at treating
34:15with chemoembolization.
34:16We can see that you get much better
34:19local tumor progression and overall
34:22survival when combing CT is used.
34:25And then we look at adverse events.
34:28We always tell patients that this
34:30is a liver directed therapy.
34:32However,
34:33their study that came out of Johns
34:35Hopkins back in 2008 showed that you
34:38can get systemic effects from the
34:41chemoembolization or conventional tastes,
34:43and this is what led to the institution
34:46or development of drug eluting be tastes.
34:49So the idea here?
34:51Is that the chemotherapy is then
34:53loaded into beads and added to
34:56water soluble contrast and can act
34:58as a vector for drug delivery and
35:01embolic agent to block arterial
35:03blood flow or supply to the tumor?
35:06As we discussed.
35:09The actually just you're aware
35:10that Luppino has some limitations
35:12where their attention is variable,
35:14and it could wash out quite rapidly
35:17if we don't use those particles.
35:19And then, like I just showed,
35:21there could be some systemic toxicity.
35:24So with drug alluding beads you can
35:26get predictable retention and this can
35:29lead to overall less systemic toxicity,
35:31and this is just a case that I did awhile
35:34back showing a force .6 centimeter tumor,
35:37which we did with drug eluting beads.
35:40However,
35:40you can't see at the end of the
35:43procedure that the tumor was treated,
35:45because there is no iodine in
35:46these particles and then this is
35:48what it looks like afterwards.
35:50So this is just a couple of.
35:52I have a couple of studies
35:54which show the benefit of.
35:56Of drug eluting beads.
35:57I don't want to get into all the details,
36:00but just show that there
36:02are promising results,
36:03but in my personal opinion I am much
36:05more a fan of using conventional
36:07rather than dip tastes and then
36:10this is just a recent study
36:12published in radiology which is a
36:14prospective single arm study which
36:15also shows the benefit of idarubicin
36:18alluding beads for the treatment of
36:20patients with unreflectively CC.
36:22So there's been a lot of
36:24interest in recent years
36:25in radio embolization.
36:27Here we have an implanted radiation
36:29source that's directly sent to
36:31the tumors via the attic artery.
36:33Use Yttrium 90 as the source,
36:36which is a beta emitter which penetrates
36:39only 2.5 millimeters in the tissue.
36:41There are glass and resin
36:43microspheres available.
36:44These are thera spheres or Sir spheres,
36:46but I just wanted to make sure you're all
36:49aware that these are not interchangeable.
36:52They're very different products
36:55and they have very different.
36:58Characteristics the main idea, I guess,
37:00is that the glass beads are have
37:03a much smaller number of spheres,
37:05so each year themselves is much hotter.
37:08So if you want to treat a much larger area,
37:12you may need to use something
37:14which is much more embolic than
37:16than than these very small ones.
37:19But again,
37:19these have much less activity per sphere,
37:22but here you get a much more minimal embolic,
37:26which is much more like
37:28real radiation therapy.
37:29Whereas the Sir spheres are
37:32more like embolization.
37:34So this is just a case of a 92
37:36year old female with multifocal HCC
37:38who actually had a tumor rupture.
37:41Um, here in in segment 8 with the
37:44satellite tumor as well,
37:45and as we know,
37:47when patients have tumor rupture,
37:48they have a very dismal prognosis.
37:50So like I said,
37:51this is a 92 year old female an because
37:54I did this with with therasphere for
37:57example it was a micro embolic Ann.
38:00I treated her as an outpatient.
38:02OK, so here is the tumor.
38:04We do a mapping study,
38:06so this is the difference.
38:08When you do the other
38:09kinds of chemoembolization,
38:10you basically take the product off the shelf.
38:13At the time of the procedure,
38:15however,
38:16with 190,
38:16you really have to map out the patients
38:19to make sure that you're not getting
38:22nontarget embolization to other
38:23areas which include extra product sites,
38:26and you also have to calculate
38:28a lunch on fraction,
38:29which is how much of the material
38:32gets to the lungs because there exist
38:35you heard earlier there are very.
38:38Small communication between artery and veins,
38:40and therefore if you give too high a dose,
38:43you can actually get pulmonary fibrosis.
38:45So in this patient we were able
38:47to see that the radiation went
38:50exactly to where we wanted to tumor.
38:52Here we see the patient for years later,
38:55so this patient lived to 98 years
38:57old and this again is the fact that
39:00I treated a 92 year old patient
39:02with an outpatient therapy.
39:04I kind of thought was pretty amazed.
39:07These are the toxicities that can
39:09occur by doing very good cone beam CT.
39:12This actually highlights the
39:14reason for it that we can reduce
39:16the toxicities by doing all these
39:19advanced imaging techniques.
39:20This was just the case.
39:22I want to show it with the utilization
39:25of cone beam CT where on cone beam
39:28CT we see in this patient a retro
39:31portal artery that on mapping study
39:34we can see some technetium 99 M.
39:37Maa actually getting into the duodenum.
39:40So if you were not care if you
39:42were if you were not careful,
39:45you would actually send radioactivity down
39:47there and that would result in an ulcer.
39:50So what I want to also highlight here.
39:53Is that? Now a recent article came
39:56out talking about recommendations.
39:59A standardized recommend.
40:00Nations 4Y-90, in this case,
40:03resin microspheres and what they say
40:06is that if you do not use cone beam,
40:09CT or advanced imaging techniques that
40:12that companies or vendors that are
40:15supporting clinical trials won't actually
40:18want them as part of one of their sites.
40:21OK, this just shows some data from Europe
40:25on those patients that are all within
40:28all across all the PC else stages.
40:31I'm in this particular study.
40:33You can see the median overall
40:36Survival's in a PCL CAB&C.
40:39Residents, although common,
40:40are fatigue, nausea, vomiting and fever.
40:44There's the GI ulcers are very uncommon
40:48and as well as grade three biliary.
40:52Issues.
40:54And you know one of the most
40:57prolific users of Y-90.
40:59This is North data from
41:01Northwestern University,
41:02where they looked at their first
41:041000 patients over a 15 year period,
41:08and you can see all the
41:10classification systems, child,
41:12child, Pugh,
41:12AB&C where you see BCLCAB&C,
41:15and they've even treated patients
41:17with PC LCD and then with those
41:20patients that had child Pugh A&B.
41:23These are the overall survival rates.
41:26And you can see they have
41:29very low adverse events.
41:30So based on their experience
41:32with 1000 patients over 15 years,
41:35they use radio embolization as
41:37their primary treatment option
41:39and then this just shows.
41:40And this is something that I
41:43think we basically treat probably
41:45less than I think we should.
41:47We start tumor board is patients
41:49that have portal vein tumor thrombus.
41:52This just shows the overall benefit
41:54of those patients that with Y-90.
41:57And I also believe conventional
41:59tastes do a good job,
42:01at least getting into the tumor vasculature
42:04of these portal vein tumor thrombus.
42:07They're having some advanced
42:09radio with embolization concepts.
42:10When we first started
42:12doing radio embolization,
42:13patients got whole liver infusions.
42:16However,
42:16overtime with patients getting
42:18going into liver failure and
42:20having really severe fatigue,
42:22it's turned into a originally low bar.
42:25Infusions OK,
42:25which you so from here to
42:28here and then overtime.
42:30The idea was that we can maybe get
42:33segmental infusions and then ultimately
42:35get the infusion directly into the.
42:38Into the tumor,
42:39provided that there is a single
42:42or maybe two feeding arteries.
42:45So here we talk about radio radiation,
42:48lobectomy OK,
42:49and this is a way that we can
42:51hypertrophied the liver prior
42:53to resection while still keeping
42:56control of the tumor.
42:57So the idea here is that we can
43:00generate future liver remnant
43:02hypertrophie that permit resection,
43:04allowing for a biological test of time.
43:07And as you may have seen from
43:09the previous patient,
43:11the previous slide we can permit
43:13patients with portal vein tumor
43:15thrombus to maybe be converted to even.
43:18Being resectable the pathophysiology
43:20of this is that you are getting
43:23some scarring and fibrosis of the
43:25liver in the side that was treated,
43:28and therefore you're getting compared to
43:30Tori hypertrophy of the untreated low.
43:33That being said, the treatment changes
43:36are comparable to portal vein EMBO.
43:38I'll beat it. Invite at a slightly lower,
43:41slower way, but it does have
43:43the benefit of tumor control,
43:45which portal embolization doesn't,
43:46and then we can talk about
43:48radiation segmentectomy,
43:49which is directly getting which is
43:51supposed to be a curative treatment,
43:54similar to ablation,
43:55where you treat up to two panic
43:57segments with a low bardo.
43:59So you're basically taking this large
44:01dose that you do for the whole lobe,
44:04and putting it into one or two segments.
44:08OK, you get much higher.
44:13Active activity to each of those areas
44:15and in some cases it's been adopted
44:18as first line transarterial therapy.
44:19So the idea here that is that it
44:22really needs to. In my opinion,
44:24it really needs to be more validated,
44:26but you can see from this case that you're
44:29placing the catheter right up to the tumor.
44:32The tumor here is completely hot
44:34and then after six weeks later you
44:37see complete necrosis of the tumor.
44:39So I also wanted to focus on
44:42portal vein embolization.
44:43This is a transvenous therapy supportively,
44:45and embolization is is that it's a way
44:48of redirecting portal blood flow to the
44:50future liver remnant and by doing so
44:53could initiate hypertrophy of the non
44:55embolize segments and by doing that
44:57can reduce perioperative complications
44:59such that we can increase the number
45:01of potential surgical candidates who
45:03have what we call marginal anticipated
45:05future liver remnant volumes.
45:07We can also achieve looks like similar.
45:09Survival rates surgical
45:10patients not requiring PV.
45:11Now Kevin Billingslea spoke
45:13about this a month ago,
45:14so I didn't want to focus too much on it.
45:17But this is just a case of a patient
45:19with HTC 10 centimeter solitaire E mass.
45:22But you can see here we perform volumetry
45:25in patients that have cirrhosis,
45:27but normal underlying liver function.
45:29We need about 40% of the remaining liver
45:32after surgery, so this patient had 33%.
45:34I don't want to get into all the
45:37like how you measure it exactly.
45:39It's kind of beyond the scope here,
45:42but basically this patient did
45:44not have sufficient liver.
45:45A sufficient anticipated future
45:47liver remnant.
45:47So this patient was considered
45:49a candidate for right Pve.
45:51We do write PVE,
45:53we do Pve.
45:54Cricket Aneus Lee where you
45:55puncture into the right portal
45:57vein and ipsilateral approach.
45:59We infuse particles and coils and we
46:01can see that there's complete diversion
46:03of flow from the right into the left.
46:06We do the volumes and this
46:08patient increased their size,
46:10their liver and 18% so this patient was
46:13considered a candidate for right hip.
46:15Protect me and this is how the
46:17liberal looks intra,
46:18procedurally or interactions
46:20intraoperatively where you see a
46:22very atrophic right lobe and a very.
46:24Hypertrophic very pinkish.
46:28Left lobe so this patient underwent
46:31a very uneventful hospital course
46:33after surgery,
46:34but developed recurrence at five years,
46:37but then underwent
46:39successful transplantation.
46:41A little bit of data on this.
46:45This is the only prospective
46:47clinical trial looking at PVE and
46:49in the setting of injured liver.
46:51It's the only clinical trial that
46:54will be done because there's those.
46:57Surgeons and interventional radiologist
46:59who believe that it's unethical to submit
47:02to subjective patient to a procedure
47:04that they think or I should say,
47:06not subject to patients to a procedure that
47:08those surgeons and radiologists think work.
47:11And then if a patient dies because
47:13they went into liver failure,
47:15that will be a problem.
47:17So this just shows how using
47:20Portal vein embolization.
47:21Actually improves patients
47:23postoperative course.
47:23This was a study that we did at MD
47:27Anderson where we see that all of
47:30the deaths occur in those patients
47:32that did not have Pve and then
47:36in terms of survival outcomes.
47:38We have,
47:39you can see that there are pretty
47:42similar those patients to those patients
47:44that have deviated to those that didn't.
47:46Now what we need to understand
47:48is that those patients that did
47:51not I should say that received
47:52portal vein embolization.
47:54Those patients typically would
47:55not have been a certain would not
47:58have been a surgical candidate,
48:00would have probably undergone
48:01a transarterial therapy,
48:02and the numbers show that those
48:05patients would probably have a 20
48:07to 30% three year overall survival.
48:09So just by doing the Pve and
48:11getting the patient to surgery,
48:13the patient had a much better outcome.
48:15So when we look at the staging
48:17system which I discussed in the very
48:19beginning and by understanding all
48:20the different procedures that we can
48:22offer at all the different stages,
48:24we now see that those patients
48:26that have very early or early
48:28stage disease can result in.
48:33Major stage be can have a greater
48:36than 2.5 year survival and then those.
48:39Of course that have advanced in terminal
48:41stages obviously don't do as well,
48:43but this just shows a recent.
48:46This is from a recent Journal of Hepatology
48:49Clinical Practice guidelines from Easel
48:50that there is really the newest thing.
48:53So I just wanted to pretty much finish
48:56up by some things that we're doing now.
48:59Some new therapeutic approaches and I want to
49:02discuss immunotherapy and interventional on.
49:04And how it interacts with interventional
49:07oncology so we all know that
49:10immunotherapy plays an important
49:12role in malignant tumor treatment.
49:15In particular.
49:16Immune checkpoint inhibitors have
49:18promising clinical applications and we
49:21also understand that monotherapy only
49:23benefits a small portion of the patients.
49:26So for that reason,
49:28combination of different immune
49:31checkpoint inhibitors with
49:32different mechanism of action.
49:34Have been utilized.
49:36However,
49:36despite this there's been a
49:39increase in the incidence of immune
49:42related severe adverse events,
49:44so in some cases a lot of patients
49:48may not be really amenable to this.
49:52We know that our interventional oncology
49:56therapies do elicit systemic immune response.
50:00However,
50:01these responses may be too weak to prevent
50:03local recurrence in distant metastases,
50:05and it's really unclear how we
50:07can regulate the immune system
50:09through these different mechanisms,
50:11and this is a you know from a paper
50:14from current oncology reports in 2020,
50:16which shows a very complex.
50:20I used paradigm in how we know therapy can
50:23be used in the setting of chemoembolization,
50:26radioembolization, inflation etc.
50:28So there is an opportunity for
50:30potential synergy with these
50:32checkpoint inhibitors with some of
50:34the therapies that we can offer.
50:36And this just shows how taste and
50:39ablation and even breakey therapy,
50:41really can result in both
50:43immunostimulation an immune suppression.
50:45I don't want to get into
50:47all the details of this,
50:50but basically it's something where we
50:52can utilize the intervention oncology
50:54therapies in order to really delve
50:56into how we can treat patients much
51:00more effectively with immunotherapy.
51:02And then this just shows that
51:04there are numerous ongoing studies.
51:07Looking at the combination of immune
51:10therapy with locoregional therapy and
51:13this is a study I just wanted to show
51:16one that just got activated two days ago.
51:19At Yale Cancer Center,
51:21which probably need to discuss soon.
51:23If Mario allows me to at our upcoming
51:26one of our upcoming tumor boards,
51:29which is the Merkley 012 clinical trial,
51:32which is basically taste is the backbone,
51:35with or without, you know,
51:37therapy,
51:37which in this case is is pen bro
51:40plus at multi kinase inhibitor
51:42which is live at and if so each
51:46patient will get taste and then they
51:48may or may not be randomized.
51:51Those they get the systemic
51:53therapy and those that don't,
51:54but we can go into that another time.
51:57And Lastly,
51:58I just wanted to show that
52:00we do treat other patients.
52:02I just have a couple of cases to
52:04show that this is a patient with
52:07colorectal cancer that followed.
52:09They failed multiple
52:10chemotherapeutic Regimen's who was,
52:11as you can see,
52:13has innumerable tumors with with this
52:15colorectal cancer did have normal
52:17underlying liver function and we
52:19treated this patient with white 90
52:21and you can see that there's a clear
52:24impact on the tumor response and I
52:26don't want to go into all the surf locks,
52:29data and all that,
52:31but just be aware that.
52:33We can do it for this.
52:35This is a patient that was referred to me.
52:37Well,
52:38it was a Cornell from a radiation oncologist.
52:40Actually with chair who had breast cancer,
52:42liver,
52:43Mets.
52:43And as you can see it's really
52:45really overtaking the liver.
52:47I was asked to see if we can really
52:50do anything for this patient and we
52:52did why 90 the page and then this
52:56was a situation where the patient
52:58was able to see even though she
53:00did succumb not within a year,
53:03she was able to see her son's
53:05wedding and also spend their her
53:07last Thanksgiving with family.
53:09So again,
53:09this is where the palliative nature comes in.
53:12And then Lastly,
53:13this is a patient with pancreatic cancer,
53:16who we were able to.
53:18Treat with conventional tastes in
53:19a term that I call like just like
53:22radiation segmentectomy something I
53:24call now chemoembolization segmentectomy,
53:26where we can actually you know,
53:28in pancreatic cancer,
53:30we know these patients have very hypo
53:32vascular tumors in a very dismal
53:35plastic fibrotic tumor structure
53:37where if we can treat the entire segment,
53:39the tumors cannot live, so that's
53:42something that we're also looking at,
53:44so I wanted to make it clear that you
53:48know HCC is not the only thing we do.
53:51If you do have patients that have
53:54other types of tumors, we're actually
53:56able to really treat those as well,
53:58and we're happy to speak to you about them.
54:02So in conclusion, I hope I demonstrated
54:04their local regional therapies do play
54:07an important role in the management of
54:09both primary and metastatic liver cancer.
54:12They often provide benefit for survival,
54:14local tumor control,
54:15and improve quality of life compared
54:18to and in some cases, you know,
54:20compared to resection and compared
54:22to some systemic therapies,
54:24it may result in cure.
54:26In some patients,
54:27such as those that have solitaire E
54:30small HCC's and can enable patients
54:32to be bridge or down stage 2.
54:35Transplant or surgery?
54:38There's various sublative
54:39entrance arterial therapies,
54:40and they have very different
54:42mechanism of of actions,
54:43but I think when looking at
54:46these kinds of therapies,
54:47it's important to really understand
54:49the real true nuances of the therapies
54:52that you're either performing or
54:54requesting is a refer so that you
54:57really understand what we're talking
54:59about and how to read reports when
55:02they come out saying ablation
55:04or a key mobilization.
55:06I've also hope to have shown advanced
55:08that both advanced imaging an
55:10catheter based technology has been
55:12very helpful in treatment decisions.
55:15By providing intraprocedural guidance
55:16and therapeutic confirmation that we
55:19were able to effectively treat the tumors,
55:21and we're also now on the precipice
55:23of looking at combination therapies
55:25which appear promising,
55:27such as those found in immuno oncology.
55:30So with that I think I'll stop here.
55:36Think I was on time, but you know I'm
55:38sure we have some time for questions.
55:42Thank you very
55:43much, Sir David. For anybody has a
55:47question and type type it please in
55:50the chat and then we will respond.
55:52In the end I mean by what
55:55people may be thinking.
55:57I want to thank you for the these.
56:00Are this great review of all the possible.
56:06Approach is there.
56:08Interventional radiology can can
56:10provide for the treatment of primary,
56:12secondary liver tumor.
56:13I mean from my own point of view, I,
56:16I think you really showed the complexity of
56:19the dictation making that is behind this.
56:22It's you know, as you said at the beginning,
56:25we think in a very simplified way.
56:28Yeah, let's sub later if aid is.
56:31But in reality, you really do.
56:35Send the patient to centers that have
56:39all these possibilities, Anan abilities,
56:41and they can really tailor.
56:44The treatment of the patient to the.
56:49To amend personalized treatment
56:51to the patient, and. Great.
56:55So we have a question from even a
56:58rukundo great informative presentation.
57:01My questions and terminology,
57:03embolus therapy versus embolization.
57:05Is there any difference?
57:09Well, that's actually a very
57:11interesting question because I like
57:13to always call things emblow therapy.
57:16Now clearly there's really not
57:18a major difference between.
57:19Well, I guess the term embolization
57:22implies that similar to like,
57:24what a pulmonary embolism uses
57:26that you're taking a catheter,
57:28and your iatrogenic Lee moving one
57:31particle or or structure to another area.
57:33Now that could be with one particle, right?
57:37But that doesn't have to be with.
57:40The whole thing, so I guess emblow
57:43therapy is actually defined.
57:44Should be defined as the
57:47treatment of patients with.
57:49You know, using these transcatheter
57:51transarterial methods,
57:52but I guess embolization doesn't
57:55necessarily have to be therapeutic.
57:57So that's actually a great I
57:59think about that all the time.
58:01And you know when we talk about in reports,
58:04for example, embolization of that,
58:06would you know?
58:08And I think that's the actual.
58:10That's the actual difference.
58:14I come. Baby, do you have?
58:19Can you expand a little bit of
58:22the possible adverse effect of
58:25combination therapy with the. They
58:28send the email uncle immunotherapy.
58:33Well, basically we don't know
58:34that yet, right? I mean,
58:36that's why we're doing these.
58:38That's why we're doing these studies.
58:40I mean basically.
58:43We also we also don't know if you
58:47should do the if you should do the.
58:51There are which therapy used to 1st right?
58:54Like should you do the should you start
58:57with taste and and then follow it with
59:00immunotherapy or should you start with
59:02your therapy and then do the taste right?
59:05You know each. I guess trial is
59:08very different, right? And each.
59:12I guess therapy has its own company,
59:15has its own adverse events.
59:18The thought is that you would
59:22do the immunotherapy. You know,
59:24after the at least two weeks you would
59:27do the therapy immunotherapy after the taste.
59:30That by then the tastes adverse events
59:32should already be taken out of the equation.
59:35Because in the time that you're
59:38getting the immunotherapy,
59:39those patients would already
59:40be beyond that time.
59:42So in terms of the actual combination
59:44is kind of hard to understand. I mean,
59:47particularly in the Merck study where.
59:50Pizza getting taste first.
59:52So you know, we still don't know.
59:55I mean,
59:55we're still very early in in all of these,
59:58you know, in all of these studies.
60:00So I.
01:00:00I don't have a very good answer yet.
01:00:04Switch an ATC and different
01:00:07histopathology dash subtypes
01:00:09with different molecular bases.
01:00:12Do you predict?
01:00:15If there is a possibility that the
01:00:17different subtype of ACC can be
01:00:20treated differently by locoregional
01:00:21therapies and they, I would have
01:00:24to say the answer is yes.
01:00:26The reason why I think that is that
01:00:28there's a very big difference is as
01:00:31you know in colon cancer and right
01:00:34sided versus left sided colon cancer
01:00:36and actuality when there's been studies
01:00:39out there that with colon cancer
01:00:41that there's when patients get why
01:00:4390 to deliver in patients that have.
01:00:46Different types of colon cancer.
01:00:48They actually get different.
01:00:51Response rates.
01:00:53So that way you would actually be able
01:00:57to tailor it so I do believe that in time.
01:01:01You know, as I said,
01:01:03I mean right now we're only like 40
01:01:05years into really treating patients with
01:01:07these kinds of therapies for liver cancer.
01:01:10So which means to me that in 100 years
01:01:12we're going to be so far advanced that
01:01:15I don't see how you wouldn't have,
01:01:18you know, genetics involved into a
01:01:20personalized treatment algorithm
01:01:21for these kinds of therapies,
01:01:22so that's what we're here to do.
01:01:25That's why we're doing the research here,
01:01:27so I think that that's a great question,
01:01:30and I think that.
01:01:31Like I said,
01:01:32we're in the we're in the infancy.
01:01:34So the agency is acquisitively
01:01:37rather sensitive. How do you
01:01:39decide between taste and why? 90?
01:01:42Because in certain institution actually
01:01:44went 90 is preferably with days.
01:01:47Can you comment? So I thought
01:01:50I had a slide and an and where it went,
01:01:55which was a meta analysis of. And actually,
01:01:59the slide said how to decide now?
01:02:01Maybe I went through.
01:02:02Maybe I clicked the button too fast,
01:02:04but at the end of the the taste.
01:02:08Question I thought I had a meta analysis
01:02:11lie which basically shows that there's very
01:02:15similar outcomes in both taste and MY90,
01:02:18so you know the way that we've
01:02:22used to think about it is that.
01:02:25In in, in patients that were older patients
01:02:28that you know we want to do it as outpatient.
01:02:32You know, back then,
01:02:33those were all considered.
01:02:34You know why 90 patients?
01:02:36OK? Now we do taste all the
01:02:40time as outpatient as well.
01:02:42So when I'm looking at it I'm looking at,
01:02:45I guess the.
01:02:47The I guess you need to look at the patient.
01:02:50In general the performance status you need
01:02:53to look at is it low bar or BI lo bar.
01:02:56You have to look at how you're going to like.
01:03:00If tumors are all in different locations
01:03:02where you have to cherry pick each each one.
01:03:05Sometimes you opt for.
01:03:07Radioembolization or the other
01:03:09one so so basically.
01:03:11If you have if you have
01:03:15multiple tumors in in a lobe.
01:03:18And you're doing radio embolization.
01:03:21You either have to treat the whole lobe.
01:03:26OK,
01:03:26which is a very big low bar taste or
01:03:29you have to do all of this difficulty
01:03:32which is changing out catheters,
01:03:35splitting doses.
01:03:36You know it's very complex
01:03:38the way the anatomy is OK,
01:03:40so the other thing I said is that
01:03:43sometimes you have patients where
01:03:45you don't know what you want to do
01:03:48and chemoembolization or the other
01:03:50embolization is besides why 90.
01:03:53Are ones where you can get them.
01:03:56You can get the product off the shelf.
01:03:59OK,
01:04:00so instead of having to order it and
01:04:03and waiting and all that kind of
01:04:05stuff so you know there's a lot of
01:04:09different opportunities for treatment.
01:04:11Unfortunately, and this is where.
01:04:15You know, institutional.
01:04:16I guess expertise comes in
01:04:19is that there is no answer.
01:04:22OK, there really isn't, and you know,
01:04:25I, as we've discussed in the past,
01:04:27I personally believe taste is a great
01:04:30option for portal vein tumor thrombus,
01:04:33because you know,
01:04:34if you look at a lot of the
01:04:37Asian publications,
01:04:38you can see the actual apidel
01:04:40sitting in the portal vein codian.
01:04:43OK, where it's very difficult
01:04:45to see that with Y-90.
01:04:48So I know that why 90 right now
01:04:51seems to be the hot option.
01:04:54Technically I used in figuratively
01:04:56for portal vein tumor thrombus,
01:04:58but it's a very very delicate situation,
01:05:01I mean.
01:05:03I I don't really get too much
01:05:05into the expensive at all,
01:05:06which we haven't even discussed at all,
01:05:09but.
01:05:10A lot of it is just
01:05:12institutional northwestern.
01:05:13I guess you would most likely
01:05:14get away 90 even though I do
01:05:17know they do taste so you know
01:05:19it's very difficult to choose.
01:05:22Alright, so if there are no no other
01:05:25questions, I think we need we.
01:05:28We need to thank David Matter for this.
01:05:31Very nice, informative in broad
01:05:34lecture an and keep that in mind
01:05:38when we have a patient with the.
01:05:42Metastatic of primary liver cancer.
01:05:44Thank you very much to all
01:05:46and have a good evening.
01:05:48Thanks Mary for the invitation.