So this is a different patient, there's actually, I'll tell you
the end story of this one. But solitary HCC within Milan, 63 year old male, history of a renal transplant and he may be a potential dual liver renal transplant patient. So on a seeming clinic he has a solitary 4.1 centimeter lesion near
the dome, and he has no mets so I always check for that as well. So treatment goal here is bridging to transplant, so I have a similar discussion of chemoembolization versus Y90. You could also talk about bland embolization, I tend to do bland embolization for extrahepatic vessels. So I go through the same
conversation, similar conversation. This guy is with renal insufficiency, renal transplant so I just put up here my renal sparing protocol, how I try to I know a lot of them might be theoretical help prevent contrast-induced nephropathy.
And another comment I wanna make is, he's got in multi hands MRIs, even though his GFR is less than 30, and so the odds comments on nephrogenic systemic fibrosis are related to older garmenia/g products and
with multi hands for example there aren't any known cases of nephrogenic systemic fibrosis. And my MRI radiologists are comfortable giving contrast so I had a discussion with a patient, basically just what I told you and they do fine with this. So this is the planning arteriogram and you can see that the segment
three, two and four. I can pass segment three but I couldn't get up and over into four because of the angle so I decided to treat two and four. Line spread function is a little higher, 10.3 but I also noticed this area, in my cone beam and on my arteriogram that was not there.
So right off the bat, I knew that it's like getting something from the phrenic but I was really worried about his kidney so I didn't actually go and investigate although in retrospect I would have, you'll see [LAUGH] So then I go in and give the Y90 and again you can see
that area. [BLANK_AUDIO] So one month out most of the tumor is dead except for the same area that I saw on my planning arteriogram and I can follow the inferior phrenic artery, the right inferior phrenic artery is these arrows, all the way up to the tumor to that area. So instead of waiting another two three months,
which is what I normally do for Y90, I decided to go back in. And I found the inferior phrenic and I saw the tumor and I did bland embolization. I used 100 to 300 micron embospheres stasis.
>> What would you have done if this patient didn't have renal failure and you saw that tumor and you recognized that there's extrahepatic supply when you're doing your pre Y90 mapping study, how would you do that? >> So I would try to do some redistribution so I probably would have gone into the inferior phrenic then and bland embolized at that point, hoping
to redistribute either on that day or the treatment day and deliver the Y90 hoping to get everything from the left hepatic artery. >> What would guys do? >> Well, I think we would probably do point down on treatment of the phrenic and hepatic artery. >> Would you do the same? >> There's a pre transplant patient so we had one patient go to the
OR, hot many years ago, and the resulting chaos was such that we don't do Y90 in pre transplant patients anymore. >> At all? >> At all. I guess if you guys just de-list them and then put them back on the list, but they don't wanna do that so basically we just don't use Y90 in our bridging patients.
Even though normally times over a year for HCC, every now and then, someone gets lucky. So just to avoid that problem we just don't do it. >> If we can tell prospectively from the imaging that the patient has a phrenic supply at the time of the pre Y90 we sometimes will
do actual chemoembolization of the phrenic suply at the time of the shunt study as well, just because I think the duration of response is better than bland embolization, but I think if you figure that out ahead of time you're better off doing at
the time of it. Obviously in this case you had reasons why you didn't do it right away because of the renal failure. >> How are the symptoms if you do the phrenic with chemo? >>They get shoulder pain but it goes away. >> Okay.
>> Yeah. [BLANK_AUDIO] >> All right. So, one month following the bland embo it was still viable in that same area so I got him back again [LAUGH] poor guy.
I decided to do convectional chemo to the left hepatic artery and this is my pre-procedure and post-procedure medications, based off of the pen protocol. Not everyone gives antibiotics, I don't know if you guys do.
I'm the only one at Jefferson that does, my colleagues do not. And with patients with renal failure actually with him I only gave zosyn the one dose because of his renal insufficiency. And then the catheters I wanna use a higher flow catheter
to get a good dose of chemo in. So then you come back and you can actually see this this little vessel here going up to that area, cone beam shows that well. I get a post treatment CT, not everyone does that, especially when
you're first starting off is really helpful for future treatment planning if you can see how much of your tumor got picked up everything, or you can do a cone beam at the end as well. And then one month following, no viability, four months following,
still no viability, decrease in size and I actually got an email today saying he just got transplanted so that's good. >> Yeah. >> [LAUGH]
So here is a different one, a larger HCC with satellite lesions, so 65 year old male,
no known liver disease. He was on statins and his LFTs were off so they did some testing and then they found this bilobar HCC and biopsy was performed cuz he doesn't have underlying liver disease to confirm HCC. So there is the lesion, it was 15.9 centimeters on MR but on CT 10.9 centimeters and there is satellite lesions bilobar
but there was no vascular invasion. So technically he is BCLC B but I wouldn't TACE this or bland embo it because I would feel like it would require multiple, multiple, multiple treatments and it'd have a huge post-embolic syndrome. So, I talked to them about Y90,
I talked to them about sorafenib and then Jefferson we have this STOP-HCC trial which combines sorafenib and Y90. Would you guys have thought about chemo? >> Sure. There's no reason not to.
I know why you'd think they would get terrible post-embolization syndrome because there's no correlation with tumor burden and post embolization. The only thing that affects the severity in duration of post embolization syndrome is whether you get the gallbladder or not. Nothing else matters. So that wouldn't put me off.
I would just give the patient the option of going either way. >> So STOP-HCC trial it's for unresectable HCC. It's Y90 plus sorafenib or sorafenib alone. We discussed this with the patient, he was agreeable. And this wasn't done in multidisciplinary clinic so, the hepatologist, the oncologist and I
all three of us go in at the same time to talk to the patient about all the options and so I do the planning arteriogram and there is supply from the left hepatic artery, the anterior right hepatic artery and the posterior right hepatic artery, line spread function is 5%. So the first treatment I treat the entire right hepatic lobe, I
use 220 gigabecquerel on extended shelf life vials and that's probably the maximum I use in one area, so I did that. A month later brought him back and did the left hepatic artery and then 2.5 weeks later, he starts sorafenib. [BLANK_AUDIO]
And the other thing I wanna show you is only using 124 Gy, I tend to go a little higher now but for that protocol I go with 120. >> Do you wanna talk a little bit more about your treatment days and obviously it makes sense to use extended shelf life glass spheres with patients with high tumor burden for more spheres
and coverage. But what are your days that you will treat and how do you decide if you'll do a patient on a Thursday or a Friday with TheraSphere. >> It depends for me, on the planning day, how super selective I can get, I can get very super selective and the flow,
between how super selective I can and how the flow is, if the flow is little, not as brisk and I'm very super selective, I probably would just treat on a Tuesday or Wednesday but if I'm treating like a whole anterior, whole
posterior or whole left, I tend to use extended shelf life and there is usually really good flow. Also I might use non extended shelf life if there is a vessel nearby that I'm concerned about. For TheraSpheres I tend not to,
my threshold for coiling is much lower than SIR-Spheres but I will coil if something is close by as well. So in this patient, because of the protocol and the STOP-HCC trial, we get CTs every eight weeks.
Pre treatment 10.9 by CT, AFP was 11.4. The second treatment day, the AFP is actually rose to 17 but one month followup, the lesion's already shrinking, 7.6 centimeters, AFP's dropping.
Six month follow up, continuing improvement. Now he is 13 months out and things are truly good and he is tolerating even though. With the trial they actually start with the high dose of sorafenib. He's tolerating it well and doing well but I think usually they dose escalate the sorafenib but not for the trial.
>> He's lucky he got randomized to Y90. >> That's my biggest fear of it, but I think that's the problem with the study is recruitment. Because if it was probably slightly smaller, I would be like, no I'm just gonna go into Y90 right away and then start with sorafenib.
That's why the trial isn't doing that well because we all wanna Y90 everything. Not everything but appropriate things. >> Well, more importantly is we don't wanna just put people on sorafenib and get liver directed therapy which is why a lot of people wouldn't refuse to
be on that study. >> Yeah, and part of it is if they start progressing on sorafenib and their function is okay they come back to us. >> Anybody else participating in that trial here in the audience? No.
>> I think it will take a while to recruit because of the [INAUDIBLE]
And non functioning patients asymptomatic. He had pancreatectomy, splenectomy and metastasectomy and he was doing okay for about a year and then mets start grow in the liver
so he was referred to us. Overall labs looked great, chromogranin A is a little high, bilobar disease including a dominant lesion 8.7 centimeter lesion segment five. No mets anywhere, negative octreotide scans, he wasn't on anything else.
So discussion with patient about the different options and what Bill said earlier about holding off Y90, is a valid point but I did not, I did Y90 first. >> [LAUGH] >> Just so I'm just giving you guys information,
if they have actual symptoms, what we we do. I think it's a little aggressive. Some literature says just give sandostatin 150 sub Q before. I don't know what you guys do for this but this is what we do at Jeferson.
>> I give 500 micrograms of sandostatin sub Q, the morning of the procedure. >> Morning. >> We do 200 sub Q. >> So this is similar to what Ed had on SIR-Spheres versus TheraSphere.
SIR-Spheres is the full pre marketing approval for colorectal mets. TheraSpheres is this humanitarian device exemption for HCC so you do need an IRB for that and you can get an IRB just for HCC or an IRB that's primary and secondary liver disease. And I think the biggest thing down here is each bead of TheraSphere, each bead has much more activity than a SIR-Sphere.
So that gives you the difference, so for the same radiation you have way less beads of TheraSpheres than SIR-Spheres. And also when I look at my doses is although the dose symmetry is a little different, the
doses are much higher with TheraSpheres than SIR-Spheres even though it's less embolic. But again there is no study comparing one or the other, I really wanna do it but I have to get everyone on board [LAUGH]
So I do a planning arteriogram, and I coil the SIR-Spheres and I coil the GDA and the right gastric, it's a little more embolic than TheraSpheres. And I do left hepatic artery and right hepatic artery, and they
both go into tumor. Line spread function 3.1. So, I bring them back. First treatment I do, most of the diseases on the right, so I do this right sided treatment,
a month later bring back and do the left sided treatment. [BLANK_AUDIO] And since June 2014 he hasn't gotten any other treatments, the tumor marker gone down, size initially went up and now starting
to go down. He's currently asymptomatic and we're just watching every couple of months or more. >> It's one of the interesting diseases where if you look at the treatment guidelines for embolization of NET mets.
Basically embolization is indicative for progressive or symptomatic NETs and all the treatment guidelines basically say you can embolize any of the four possible modalities. There is no recommendation among which one you should use, and it's also if you look at the practice survey that Ron Gulper/g published in 2012, was like 260 radiologists and they asked like what agent do
you use for which kind of hepatic benignancy, NETs was the only one that was evenly divided among the four, everything else there was a strong bias toward either Y90 or chemoembolization. So we really don't know what is best we just presented a multi-centered retrospective study from 7 major US centers here about 150 patients
who have been treated however they were treated. So basically about a third were bland embolization, about a third were conventional chemoembolization, about a third were Y90. And there weren't really differences in terms of tumor control or
survival outcomes among the four in the sort of retrospective assessment. The only things that way matter were tumor grade and tumor burden. And that was basically base net information for the RedNet study which is a perspective randomized trial of the three embolic techniques that's gonna be starting later this year that, hopefully, will
tease out whether one really is different from the rest or not. But right now you can do whatever you want. >> Except well, do you wanna maybe talk about drug-eluting beads in neuroendocrine? Do you guys, do you do drug-eluting beads at all in neuroendocrine tumors?
There's concern that there may be an increased risk of bile duct injuries. I think the data is kinda weak but basically there are some reports of increased bile duct injuries especially neuroendocrine patients with drug-eluting beads. So we occasionally do it when we run out of our ability to get powder doxorubicin.
Sometimes we don't have a choice when we use it. But I think patients need to be informed when there's that situation going on. So we talk to the patients about it. >> Especially three single institution papers that suggested that an increase that happen to be
injury in NETs patients getting DEBs. And if you sort of pull all the patients of those three studies together, the incidence s about 20%, 25%. But, there's just those three papers, no one else has actually reported it and obviously a quarter of the country is using it. And you don't exactly see people refer to it as a big problem then
some of them meeting here said they went back analyzed all the data to present at this meeting hoping to support that concept and found actually that it wasn't true at all. So, one of things that we're looking at the RedNeck studies is when their arms is drug eluting beads is very early safety analysis to see if this is really a true phenomenon,
or whether this is some random single institution misleading retrospective's papers and it remains to be determined but there's definitely some concern because of those papers.
All right so next case, this is a 72 year old man, with HCV cirrhosis, he has a large HCC with portal vein and hepatic vein tumor thrombus. He has good liver function, bilirubin is 0.4, child pugh A but he has very poor functional status,
ECOG is 2. So here's his tumor, here's the HCC, here's the portal vein thrombus, this is enhancing so it's tumor thrombus and here's the hepatic vein tumor thrombus, so when we see an HCC with portal vein thrombus this sort of tends to make
us wanna do Y90. Just because if you are doing a bland embolization and you are shutting down the hepatic artery and the portal vein is also out then that could increase your risk of a liver infarct or liver failure in you are embolizing a large piece of liver.
So, even in the setting of main portal vein thrombosis if the patient is child pugh A. You can still potentially do radioembolization. So the portal vein thrombus pushes us more towards Y90. The other issue for this patient is his poor functional status. So we saw this before, we also get an ECOG on all of our patients,
ECOG zero means that they are active no restrictions. ECOG one they are walking around and doing some stuff but not fully active. ECOG two, they are walking around but not doing much around the house. ECOG three they are mostly in bed or in a chair and ECOG four they're
are completely disabled. So for me, for bland embolization I usually use a cut off ECOG of up to one, and then for Y90, I'll go up to an ECOG of two. And I think its just because the Y90 is a little better tolerated. It's done as an out patient procedure.
There's less post embolization syndrome. So for someone with border line functional status, Y90 might be better tolerated. So in terms of Y90 versus bland embolization the Y90 of course is done as an outpatient,
but you have to do the mapping and order the dose first. So if you have a tumor that's growing quickly and you wanna treat it immediately and it's a tumor that could potentially respond to bland embolization, that might push you towards bland embolization because you'll be able to treat them immediately.
Of course the bland embolization has more post embolization syndrome and they're getting admitted for the most part, Y90 is more expensive and in terms of what we're treating, for the most part bland embolization we're using on hypervascular tumors like HCC,
neuroendocrine tumor, melanoma and then Y90 were using on we're using on hypovascular tumors like colorectal liver metastases. And of course the Y90 we can treat the main portal vein thrombus if they have good liver function. So in this case because of the functional status and the portal vein tumor thrombus we did Y90, treated the right hepatic artery and got a good response. >> So what was the shunt in this case? >> I think it was under 10% I don't remember the exact number. >> Right, you wanna talk a little bit about how you handle higher shunt fractions and people who have vascular invasion? >> Yeah, so the shunt fraction is greater than 20, you could reduce the dose or you could just not treat them and do bland embolization instead. >> You ever put him on sorafenib and redo their shunt study? >> I personally have not done that, have you seen good results with that? >> I've never done it either but other people have, and said if you put on sorafenib for a month and then redo their shunt study that the shunt fraction will go down after the entire androgenic therapy. >> You can also do bland embolization or TACE and then redo a post study and see what the shunt value, it usually goes down as well.
>> I would just add that there's not an absolute cut off for shunts or 20% is high but that doesn't mean you can't treat the patient, you have to do the volumetrics and dosimetry and if the patient doesn't have COPD or something where you're worried about you can go up to the maximum lung dose, and if you're getting a therapeutic
dose into the tumor at the maximal lung dose, you can still treat people with 20 to 25% shunt fractions as long as. I have a lady whose got really bad COPD and has had 22% shunt and I decided not to do Y90 on her cuz she had hepatic vein invasion, and we're trying
other things first and then come back to it, but there is no magic number you have to plug in the numbers and see what you can get and usually we just go up the maximal lung dose and you can still get a therapeutic dose in the tumor. >> I think that I can comment on,
I think you frequently here this philosophy that patients with microvascular invasion sort of get Y90 versus chemoembolization because somehow the smaller reactor microspheres will get into the tumor thrombus better, but that's basically marketing as far as I know, there is no real
data to support that concept. I think if you are doing lipiodol based chemoembolization the liquid emulsion will go right in the tumor, I mean it's an arterialized tumor thrombus and you'll see the lipiodol uptake in the tumor thrombus. You could actually get complete responses in the tumor thrombus to conventional hepatomized chemoembolization.
So, you know, there are other factors that might tip you between re-embolization, chemoembolization but I don't think vascular invasion is really one that should play into it. The other comment i'll make is one of the comments you said was in deciding between the two, whether you want a quick response or not might influence your decision but the other person in the room is the patient,
and you should ask the patient what they want cuz maybe what the patient wants as a quick response, as opposed to what you want. And so what I tell patients is for the average patient with no big factors that the medical benefit and
the medical risk of chemoembolization or embolization is the same. You don't know how it will work on that patient, but on average they work similarly well and they're similarly safe assuming that there's no other mitigating factors, I can tell them can be quick and sick or you can be slow and glow.
It's up to you. You can pick your poison. We'll start with whichever you want, I'm happy to do it, and if it works well, we'll stick with it and if it doesn't work well we can still do the other one.
You haven't burned any bridges. I hear a lot of people say, oh I told them to get Y90 cuz I they won't get sick. I said, how do you know that's what they want? Most patient want their cancer dead and frankly if they have a little
pain and nausea and in the hospital overnight, it's worth it to them to know that tomorrow the cancer is dead as opposed to getting Y90 a month from now and waiting three more months to find out it didn't work. So, patient preference does come into play.
It's not only a medical decision, in most patients it's really a patient preference decision in terms of quality of life issues and for some patients the quality of life has improved knowing that cancer has been treated as opposed to knowing they'll be done as an out patient.
>> Yeah, so we also do bland embo in the setting of segmental portal vein thrombus. >> How many people have Y90 programs at their institution? Raise your hands. Okay, so far less than half, and how many people have glass microspheres, and how many people have resin microspheres?
Some people don't have either. >> [LAUGH] >> I don't know what the other option is. >> Maybe we have both but we just follow regulatory guidelines and doing it since we are training program so our HCC patients get TheraSphere
under the HDE and all our meths get stratospheres but we basically just do that cuz we have it and we wanna train the fellows in both, and it's compliant to do it that way so we can do it [INAUDIBLE ] >> Same thing although I'm working on getting an IRB to use TheraSpheres for primary and secondary.
>> So we have both and we have an umbrella IRB that allows us treat any patient with either of the devices and we pick the device based on the tumor, the characteristics of tumor burden and sort of patient characteristics with regard to the capacitance in the blood vessel like a metastatic cholorectal patient who's had tons of chemotherapy and has really beat up blood vessels.
We may have had a hard time getting an adequate dose in with resin so we use glass in that patient, so we don't really pay attention to the label indications so we do it on patient's characteristics. >> You decide after? >> After the shunt study,
yeah, we decide after the shunt study.
I think I've heard a lot of that today.
So here is the lady that I'm gonna show today and it turns out, I had a lot of cases that I was going to present but her's is nicely incarcerating and includes a lot of stuff. One of the things that is important for us is that I didn't put it here but I wanted to share that she's 60 years old and was referred by X clinical doctors.
Keep that person's name, talk to that person, work with that person, it works amazingly well. So it's always in the counsel in the first line. I just have where she had her cancer, whether the lesions were synchronous
or not, whether she's KRAS, wild or mutant. Because KRAS mutants don't respond to cetuximab. So you have to know that if you're gonna try to figure out what sort of chemotherapy they're gonna get. When the primary tumor was resected if it were,
cuz that's important. And so it was resected about eight months prior to that. And what chemotherapy the person had. All these stuff matters as you're trying to figure out what to do to this person. And that's kinda where it came into device selection.
Thing is that, I know this is a lot of stuff, it doesn't seem relevant. It's completely relevant. If you're gonna do this right, you have to pay attention to all of these stuff.
And I think we gloss over that and a lot of things as we go straight into device selection and hope that this stuff is gonna follow. And it doesn't. This is the hard part. This is the concerning part and you really have to deal with it. But I think it really makes you a better interventional radiologist
and better able to check your selections. Also, here is what her symptoms were. She has her neuropathy that you get when get oxyplatinin, and she's anxious. And that's not a surprise.
But she's ECOG zero. You can see her past medical history. Nothing was major but she had 20 medications. None of them was gonna cause her to be coagulapathic then and give her a problem. You've gotta pay attention to them none of them were a bit most
of them were vitamins, no allergies she didn't have much of a surgical history other than her resection you wanna look at her physical exam and then look at her labs and as I said don't treat with Bilirubins they are elevated. And then here is her PET-CT which is the reason we went ahead.
This is actually from May because even though with in my institution they always do contrast enhanced CTs with the pat which I think is invaluable. Frequent in other places you just get an non-contrast pattern. It's so much less valuable. So in this case I put the old CT up with the relatively new pattern.
You can see posterior thing there that, right there, it's actually seems to be in the center of the liver and that's why I put it up in the coronals cuz when you see the procedure then you understand why. This is the culmination of it is that we talked to her,
she's got just the one relatively big lesion that's not a minimal to the ablative therapies, in our opinion, synchronous tumor makes her prognosis a little bit worse but she's KRAS, Y type she's got lines
of chemo available, we talk about it, we also mention if I'm planning to use glass, which in this case I did that we put in our consult note that it's under a HDE and we've discussed that it's gonna be managed by the IRB/g, we talked about the alternatives including
drug eluting beads which I say I just don't like as much. Basically I think it's not as good but that's my opinion. Risk to the procedure which I have already talked about, our expected outcomes and our goals.
What's our next step in this and that's I think the direct echo of what you said. So with that then we'll move on to UNS Skip U right.
is the lady that I talked about before, 60 years old, progressing metastatic
colorectal cancer in the center of her liver. And here is her celiac arteriogram and you can see that she has kind of weird anatomy, she actually has a left that provides a left hepatic, and then provides to the five, six or six, seven, and then the other one's coming off from a different place. So the supply to her right lobe was kinda bizarre, but I
thought that both of her right lobe arteries supply the tumor. So from that I decide I was going to, and you can see the tumor-ish in the centre of the right lobe. So I decided I was gonna split the dose and put one in the five, eight and one in
six, seven. So here's the technetium study, looking like I'm gonna probably do okay. There was about a 4% lung shunt from that, then you take your past imaging. You can do it off of this volume/g which offer many things. At our place we always use the CT scan, we believe it's a really accurate volume for the extent that you need it for this, because we really don't know what
the right dose is. But we decide that it's somewhere between 100 and 120 grey. So we use that, use the lung shunt fraction, use the dosimetric charts, which look way more complicated than they really are, and calculate the dose that we're gonna deliver, and then on the delivery day, deliver it. And that's to one of the blood vessels, and then that's to the other one I think, right there. So both of them
supplying the tumor. Then we take them over to PET scan, show that it went to tumor. We've just published here, in like an hour we're gonna talk about this exact situation and she'll be one of the patients, is that we can calculate the dose of
Y90 to the tumor from the PET scan. So you can count the dose, you can count the activity. And we know exactly what we give to the tumor. So we think that's a benefit because you really don't have that degree of quantification and we don't have a standardized procedure with everything else.
So I believe this is sort of like one the one steps forward that Jaffar was talking about. Is that if we can say, this is what we delivered, here's how we got it there, here's how much went there, and here's the response. That's gonna actually be fairly impressive and allow us to do patient
centered medicine. So that's the whole procedure, patient goes home. Like I said no medications other than the PPI's and they often take the pain meds or some of the antiemetic but that's
cholangiocarcinoma. She had a left hepatectomy and she now has a three centimeter recurrence
at the resection margin. She has good liver function, bilirubin is 0.8, child pugh A and good functional status, ECOG is zero. So, here's the tumor,
you can see the resection margin here and here's the three centimeter recurrence. So the options for treating this you could do ablation, bland embolization, Y90, now the location is not great for ablation, it's next to the IVC, next to the heart, so not a great ablation
candidate. In this particular case since it's sort of a hypovascular tumor, we decided to do Y90 and so they've had a left hepatectomy so they only have a right hepatic artery and on the angiogram, this is the right hepatic artery and it turns out that this tiny vessel
here is what's supplying the recurrence. So I spent a lot of time trying to get into this vessel and could not get into it so the question at this point is if I can't get into this vessel, should I embolize the entire remnant liver. I think you could potentially do it.
You don't wanna do it because there's gonna be a higher risk of liver failure, so what I ended up doing is protecting some of these off target branches by embolizing with gelfoam and then I delivered the Y90 to the right hepatic artery. You can see on the Bremsstrahlung
SPEC CT after delivering the Y90 that the tumor is right here at the resection margin so the Y90 got to the target and protected a lot of the off target liver. So the other question here is TheraSphere versus SIR-Spheres and in this particular case we're treating a small tumor, and it's
supplied by a very small vessel and one issue with SIR-Spheres is that it's less dose for particles but there are more particles, it's more embolic, and sometimes you reach stasis before you've delivered your entire dose. So for the small tumors supplied by small vessel, you might have
better success delivering your whole dose with TheraSphere which is gonna be less embolic. So in terms of comparing TheraSphere and SIR-Spheres, the way that I think about it is that if you're worried about reflux,
if you're worried about reaching stasis before delivering your entire dose, then that might push you more towards TheraSphere, also for portal vein thrombus, if you wanna be less embolic that might be another reason to use
TheraSphere. For SIR-Spheres it's lower dose per particle, more particles so if you have a large lesion and you feel like you need a lot of particles to cover the whole thing that might be a reason to use SIR-Spheres. In terms of indications,
TheraSphere has a humanitarian device exemption for HCC, SIR-Sphere is FDA approved for colorectal mets .At our hospital we're not particularly influenced by the indications. If your IRB for TheraSphere says you can only use HCC then of course that's gonna be a restriction.
Our IRB says that we can use TheraSphere to treat anything, so that doesn't restrict us. And then in terms of insurance approval, I have had some issues, if you're treating something unusual like if you're not treating HCC, neuroendocrine tumor or colorectal mass sometimes the insurance
company won't pay for it but if they are gonna pay for it I personally haven't had any issue where the insurance company said it will only pay for SIR-Spheres or will only pay for TheraSphere. >> For a long time Blue Cross had a national non payment policy for any kind of metastatic disease other than the tumors that Edd listed and they actually just reversed that policy recently.
So it used to be almost impossible to get approval. In fact when I would have conversations with patients about chemoembolization verses Y90, I just flipped to the back of their charts and look at their insurance cuz often that determine what they got. I mean in Philadelphia, it's either Blue Cross or Medicare and so depending upon who their insurance
coverage often that determined what therapy they could get paid for. But now they've Blue Cross is when they used change policy where they will cover therapy for any liver dominant not about any but most liver dominant metastases so breasts and things that they used
to not pay for. That's a big change. When you [INAUDIBLE] assume that the rest of the liver was gonna get [INAUDIBLE] kinda the same thing. >> Yeah. I just ordered it as a whole remnant liver dose, and then assumed
that I would just deliver it more selectively. >> So you're doing a segmentectomy? >> Right. Yeah. Yeah.
epithelioid hemangioendothelioma very rare. This is a 64 year old female she had a recent history of breast cancer and then followed by lymphoma and then she had a follow up PET probably a year out after her lymphoma was treated they showed no FDG avid lesions but
four months later there were multiple bilobar FDG avid lesions. She was referred to surgery for laporoscopic evaluation, possibly ablation and resection. They did a biopsy and it showed hemangioendothelioma so they
closed her up and sent her our way. [BLANK_AUDIO] So this is five months after the PET so nine months after no, the PET was negative. And so she was asymptomatic, ECOG zero,
labs looked okay. No mets anywhere. So then I was with the task of what are treatment options and there really isn't that much for hemangioendothelioma. Liver transplantation seems to be the main stage treatment for it, for hepatic hemangioendothelioma.
Unfortunately she had breast cancer and lymphoma recently so she's not a candidate. In terms of going doing a literature review on transarterial therapy. There's a few case reports of doxorubicin based chemoembolization with up to the seven years survival with that. There's not much of anything about radioembolization or radio
sensitivity of these lesions. And then targeted molecular therapies are just starting to evolve including one that's a merck inhibitor that's used for melanoma. So me and the oncologist saw the patient together and we talked about all these things with her and she decided to go with Y90 first, I talked about TACE versus Y90 and I said there is no data saying
to do one or the other so let's try Y90. So, of course people with odd diseases also have odd anatomy [LAUGH]. So her common hepatic trifurcated into the GDA, a small little origin that went into the lateral left hepatic artery and the right hepatic artery, and a separate branch that was the
medial left hepatic artery and the right gastric. So, on the planing day I embolize the GDA and the right gastric. And, first treatment I treat her entire right hepatic lobe. Second tumor are two separate bios, I went into the lateral and media left hepatic arteries.
[BLANK_AUDIO] So, one month following she had increased size and number of lesions. Some of the larger lesions had necrosis and well this is treatment effect or she progressed between, it could be multiple things.
Treatment effect, she progress after treatment or she progress between the pre treatment scan and post treatment scan. Again I try to get a pre treatment scan within one month of treatment, to avoid that compounding factor. But in five months she had decrease in her lesions so things were looking good.
The first nine to eight months there was two lesions, so the rest were stable or slightly decreased the two lesions on the right that we're growing. So this seems to be an aggressive tumor because it popped up in four months and even within like two months it looked like it had grown.
So, back to the clinic and talked to her about chemoembolization. >> I think that the concept of sort of pseudo progression that you show here were basically because the lesions become necrotic. They become easier to see on MRCT and that's something that is difficult I think for some of our diagnostic radiology colleagues to get
a handle on. It's hard for anybody. I think you know its hard to know sometimes whether there's true progression or pseudo progression, and it's just something to make sure that when you're discussing what's going on with the patient,
with medical and college tell people that sometimes the things that are called progression certainly after Y90 especially are not necessarily progression. >> Yeah. In fact mainly we don't image it one month after because they always
look worse at one month. I think that's just a very very misleading scan, unless its gonna change what you do next, I wouldn't do that scan. >> So the reason we do it,
I went back to Riod/g a lot and asked him why, it was mainly because that's what BTG recommends and what our IRB says. So when I talk to patients about it I tell them it's because I'm looking to see places I didn't treat if anything grew there. And I need to treat that,
but that one month one is definitely controversial whether you need it or not. And so I went back to the right and I did unconventional chemoembolization and that's how I do it. I continued to be symptomatic but at one month there's bilobar bar progression so I don't think the chemoembolization helped her
much. I saw her back in the clinic and said, I don't think it's worth doing your left side at this time, let's see what oncology can offer you cuz I knew there was that melanoma treatment with Trametinib so right now the oncologists decided to just hold off treatment for now,
they're just monitoring but I think soon she's gonna start Trametinib [INAUDIBLE] And hopefully we'll keep following her and see how things are going. >> It's a terrible disease, I mean nothing really works very well for this. >> We got a little bit of stability. That's my last case.
>> Good. We have other ten minutes if want, any questions about anything we talked about or other aspects. Sir? >> Can you talk about the dose and the shelf life thing?
>> So the glass microspheres are manufactured on Sundays and you order a dose based on your treatment days. So if you treat a patient on a Wednesday in particular, you're trying to target 120 grade to the right lobe for example you'll have let's say 5 GBq vial.
And if you treat the same patient tying to get the same dose on a Friday or it might be a 10 GBq vial. And if you wait for the extended shelf life which was manufactured the Sunday before, and you treat that on that patient on a Monday, it might be a 15 or a 20 GBq vial so the number of spheres increases as you go through the week. And then you can treat with an extended
shelf life that was on a Monday or Tuesday, for example, that was done the week before and it's all a matter of trying to get the tumor coverage hopefully that wanna get to. When you're trying to hit that sweet spot of having the right number of spheres to cover the tumor and get the right
therapeutic dose in the patient and so the TheraSpheres really the regular shelf life stuff is really hot. And then you have the extend the shelf life using it the next week, it's sort of in the middle and then SIR-Sphere, the resin microspheres are on the other end of the spectrum and we sort of do the same thing.
We mix and match based on the patients tumor burden, how vascular they are, the tumors are, what the flow is like, all that kind of stuff and trying to figure it out. It's something that gives you a lot of flexibility and everything
but we almost never give glass microspheres on Tuesdays, Wednesdays or Thursdays. We're treating almost all those people on Fridays, Mondays and Tuesdays. And in the middle of the week we're doing SIR-Sphere cases on Tuesdays, Wednesdays,
Thursdays, cuz we have both, so does that make sense? >> It's crystal clear. >> What's that? No. >> So basically you're trying to nail the dose and you're trying to
[INAUDIBLE] >> There's more spheres, the longer you wait out in the week, to get this, cuz each sphere has the same specific activity and it's decaying from the time it's manufactured.
So on a Friday, to get the dose you need, you need to give a lot more spheres on a Wednesday, right? So, on Friday we're giving, it might be a vial that has twice as
many spheres than versus the one you were treating on a Wednesday. So if the patient has a large tumor burden we wanna have more spheres to try to cover everything. If a patient has, if you're doing a raise in segmentectomy and you got a really hypovascular tumor it doesn't matter, right?
There all these spheres that are gonna go in the tumor, and you're gonna kill it. It's gonna be fine. But if you're treating larger volumes, larger tumors, hypovascular
tumors, that kind of stuff, it does matter, probably. We don't have a great data but it does matter how many spheres you're giving to the patient to try to cover the territory. Does that make sense? >>Yeah, I got it.
Okay, Derrick. >> I have two questions, first do you always do Y90 [INAUDIBLE] >> We generally don't alter the target dose based on the type of tumor but certainly based on sometimes patient characteristics or liver hepatic reserve
or something like that, I don't know what you guys do. [SOUND] >> I base it basically on hepatic reserve and how big of an area so if it's a small area, even if the bilirubin's a
little higher, I'm gonna t lean towards rad/g segmentectomy if I think they can tolerate that little area going away, kinda like what a surgeon does for whether they can resect something or not, how aggressive to be.
If their bili is between two and three I tend to go 120 and lower, but if it's between one and two I tend to go like 140, 150 or do radiation segmentectomy so it's like how much can their liver tolerated and there's no specific science to it,
but that's how I base it off of how much volume I'm treating and what the liver function
so this is a 55 yer old man with colon cancer and liver mets,
but he also has a spine metastases. So this patient presented with metastatic disease so he never had his primary resected, he got chemotherapy, he got a radiation to his spine met and then the follow up head CT showed that he he had a lot of liver metastasis that were still hypermetabolic
but his primary colon tumor was no longer hypermetabolic and the spine metastasis were also not active. So the only hypermetabolic disease was in the liver. This patient had good liver function, billirubin 0.3, child pugh A and his ECOG one. So in terms of radioembolization for colorectal mets we're treating unresectable liver dominant disease,
so the question really is what is liver dominant disease and how much extrahepatic disease is too much? So if you take a look at patients who are dying from colorectal cancer and you're try and figure out why are they dying. Most of the deaths are due to the liver metastases.
So this is sort of the rational for saying that if the patient has big liver metastases, they have some extrahepatic disease but it's small, and it's stable or it's shrinking, then there might still be
a rational for treating liver metastases, that's gonna be the cause of death. So in this case we did do SIR-Speres, we treated the right hepatic artery. This is the pre-treatment PET-CT and one month after treatment we
got a follow up PET-CT. You can't see it on these slides but there was a partial response on the right and the left had a significant progression but the big problem is that there was new activity in his primary colon cancer on the follow up. So we decided at this point, it's sort of a
a grey zone but we decided that with progressive extrahepatic disease that it was no longer liver dominant and so we did not treat his other side. >> [LAUGH] >> You disagree? Well I have one more slide on it and maybe we could have a discussion.
>> Go ahead. >> So I think PET-CT is very helpful for colorectal liver mets, so for evaluating response quickly, so we generally get a PET-CT before treatment and then one to two months after treatment we'll get a followup PET-CT to evaluate response.
And that's just because that we can actually see the response one to two months after treatment on PET-CT, whereas on CT or MRI it can take two or three months to really see a response on imaging. So, if you're dealing with something that is not hypermetabolic on PET-CT such as HCC then you're not gonna be able to follow response
on PET-CT, and you're gonna have to wait two or three months to see the response on the CT or MRI. The other thing that makes PET-CT really helpful for colorectal mets is that only half of them actually show a response. So if we don't see a response on one lobe, we typically won't treat
the other lobe as it probably won't respond as well. So, thoughts on this? >> I think that's an interesting algorithm, I guess we don't have the luxury of using PET-CT as much in integrating it into the algorithm. I think we use it in our institutions much more to determine
if patients are gonna go to surgery to make sure they don't have unrecognized nodal disease or something but as far as decision making for liver directive therapy, we don't use it much and I think on follow up when you see patients at one month after Y90 at least as long as they're not progressive and often times you're
following a CEA and if the CEA is coming down or at least not rising and they're showing a least stable disease at one month you write that it's gonna take three to six months sometimes for maximal imaging response but as long as they're not progressing, we go ahead and treat the other side.
I think the other thing you think about is as far as sequential lobar approach versus whole liver in a single treatment session I think in the clinical trials we're doing, we treat the whole liver with separate infusions right and left lobe, it's safe to do that. And people who have have extrahepatic disease like this gentleman
or someone who really should be getting back on systemic therapy earlier. We're starting to do more whole liver therapy particularly like melanoma patients, patients like that who really need to get back on their systemic therapy quickly. We treat the whole liver in a single session so as not to delay
them getting back on systemic therapy. I think it's one of those things that really is on a case by case based I don't know what you guys do in your practice. >> Well, I think for colon cancer, we don't stop chemotherapy so I mean it's different for doing in salvage but if they are on chemotherapy, it's perfectly safe to do Y90 concurrently with chemotherapy.
You just have to pay attention to what drugs they are on. So the 5FU, you don't have to dose reduce and it's a radio sensitizer so it's actually good to have them on that, if they're on full flux, you have to dose reduce the external platin/g for the couple of months that they're getting Y90 so you have to coordinate
that with your oncologist. If they are on [UNKNOWN] you don't have to dose reduce a renal t-can so really the issue of keeping on chemotherapy, they needed it if they have extrahepatic disease I say just keep them on it, and we'll
just treat right through in coordination with the chemotherapy. >> No vastin. >> No vastin right, so that's why we asked them to stop for a month before we do them and stay off until we go back on again. You can do it, the extrahepatic disease issue is really a judgement call.
I think your estimate of the percentage of colorectal patients who die from liver failure is low, 53% I think is a way underestimate. I think it's probably more like 70 and the other thing is, it's obviously a judgement call. You have to look at the patient and the patient's scans and you
have to say in your heart of hearts, do you think they're gonna die from liver failure or from dissemination and that's sort of subjective. In every paper we published on chemoembolization for any tumor type, extrahepatic disease has never statistically impaired survival
versus the patient you treat with no extrahepatic disease at Pem. On the other hand if you look at North Western patients, they're on your papers. Most of their papers,
extrahepatic disease did statistically significantly reduce survival compared to patients who did not have it, which to me just means we have better judgement than they do. I mean at some point if you are too aggressive doing lucrative therapy like I've said at some point you have to say
no, no. This is all risk versus benefit and you know if the benefit isn't there, it's not worth the risk. It's just a question of where you draw the line. The other phenomenon that actually Edd described was that it's not at all unusual for patients in systemic therapy to respond outside
the liver and not in the liver. So the liver is this wonderful protective place for tumors to grow where the liver detoxifies the systemic agents. So with many different types of metastatic disease, you all see the scenario where they actually may have a fair amount of extrahepatic
disease but that is all stabler responding to chemotherapy and the liver is progressing. And they will ask you to lay around liver therapy in that setting because they don't have control of the liver and they have control everywhere else. In which case the amount of extrahepatic disease is not so important because
that's being controlled by the drugs. So you kinda have to look at each patient individually. There are a lot of different factors that can play in that decision. [BLANK_AUDIO] >> That's it for my case, so Susan I think we have
some cases. >> Any comments or questions from the audience about anything we've talked about so far? There are no stupid questions except the ones you don't ask.
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