Good evening everybody, and welcome to a Thursday night members webinar. My name is Bruce Stevenson and I have the honour and privilege of chairing tonight's webinar. I don't think we've got any new folks in tonight.
So usual things, questions into the Q&A box and we will keep those over to the end. And then if we have time, Owen has kindly agreed to answer as many as he can. So for those of you that weren't with us a little while ago when Owen was with us, Owen is an RCVS, an American specialist in veterinary oncology.
He is a Cambridge graduate who spent 9 years in practise before his residency term at the Royal Veterinary College. Since 2017, Owen has worked for Highcroft Referrals in Bristol. He is interested in all aspects of oncology, but especially hematopoietic malignancies, immunotherapy for cancers, and perineoplastic disease.
Owen, welcome back to the webinar vet, and it's over to you. Well, thank you ever so much for that introduction, Bruce, and thank you to Dawn and the webinar vet team for having me to speak. It's good to be back.
And this evening, ladies and gentlemen, we're gonna talk about hemangiosarcoma. And I want to prove to you that this is a disease that is just as interesting as it is terrible. And it's also reasonably well misunderstood.
So after a brief overview of hemangiosarcoma, I'm gonna get right down to the nitty gritty and present my approach to the differential diagnosis of splenic masses with and without hemoabdomen. And that's because this is the most common place where you and I are going to encounter hemangiosarcomas and let's face it, it can be really, really stressful. I'm then gonna talk a little bit about the biology of Huangiosarcoma, and I hope to tell you a few things you may not know and why these could be clinically relevant.
I'm then gonna end by talking about the treatment of hemangiosarcoma in some detail and the prognosis. So let's get going. This is a visceral hemangiosarcoma.
OK, or rather these are visceral hemangiosarcomas, and I'd hope that we're all familiar with these. And this is a pericardial effusion caused by an atrial hemangiosarcoma. And we're probably familiar with these too.
This is an intramuscular angiosarcoma and presents as a rapidly growing and often very painful and bruised mouth. This is a subcutaneous hemangiosarcoma. Look at this poor Labrador here with this horrible angry wound there or this horrible exudative lesion down here.
And this is a dermal hemangiosarcoma, tends to look like blood blisters, maybe inflamed, maybe not. This is an intraosseous hemangiosarcoma. This is a retroperitoneal hemangiosarcoma, often presents like a huge mass causing constipation.
This is a lingual hemangiosarcoma. And so lots and lots of hemangiosarcomas are available. In fact, you can get a hemangiosarcoma anywhere where you have blood vessels.
In other words, anywhere in the body. OK? And it's useful because the aggression depends heavily on the location of the tumour.
The visceral ones, with the exception of those in the kidney are almost absolutely metastatic and very rapidly so, very, very aggressive diseases, as I'm sure we're all aware. The retroperitoneal ones which kind of hang off the musculature in the roof of the abdomen, they're similarly really, really aggressive as far as I'm concerned. The exception of the visceral ones is the renal hemangiosarcomas, which are less metastatic for a start and often slower to metastasize.
They're similar in behaviour to the subcutaneous or intramuscular hemangiosarcomas. But if any of you have seen a renal or subcutaneous or muscular hemangiosarcoma, I think you'd all agree that they're too aggressive for our liking. They're still extremely nasty.
We might be talking of a survival in the order of 10 or 12 months as opposed to a survival of 6 months, for example. The lingual hemangiosarcomas tend to be better. Now some of these we may cure.
Possibly half of them. The dermal ones though are the ones with the best prognosis and the majority of the dermal hemangiosarcomas. We see them in this country.
Bruce may be more familiar with seeing them in warmer countries like South Africa. Then the dermal ones are ones where the majority we can cure. And occasionally you get reports of them in the nose or lymph nodes and things.
The prognosis can be quite variable, but in the majority of cases, these are extremely metastatic, and they're some of the most aggressive malignancies that we see in veterinary medicine. Why are they so metastatic? Well, I think this is because we're dealing with a cancer of blood vessels, and here we have a histology picture and you can see lots of badly formed blood vessels that often end blindly and lots of vascular channels.
So we're dealing with a very, very badly formed vascular endothelium. And if any of you are doing certificates or postgraduate qualifications in medicine or oncology, you may want to become familiar with the essential bits of the metastatic process. For cancer to metastasize, all these 9 criteria need to be fulfilled.
And the first few are involved in physically breaking in to the circulation or a lymphatic vessel. Now if your cancer originated in a blood vessel, then the first few are done for you. You don't have to do those.
So for a hemangiosarcoma, you've got far fewer hurdles to overcome to metastasize. So my first key point then, you can get a hemangiosarcoma anywhere in the body. The anatomic location has a very important effect on the tumor's behaviour, but as far as we're concerned, they're all far too aggressive for our liking apart from dermal and some of the lingual ones.
That is because of the unique intravascular situation of these malignancies. You and I are most likely to become familiar with your angiosarcomas in this horrible setting. For example, it's 6:00 on a Friday evening and you want to get away because you've got plans for the week.
Weekend and you see the pesky receptionist has booked an appointment to the collapsed dog into your previously empty 100 appointment. And you find the dog has a swollen, painful abdomen and is in hypovolemic shock and pale gums and poor pulses. You do an abdominal fast scan and you see free fluid, you tap it, it's blood, and there's a splenic mass associated with it.
A very, very common and extremely stressful situation. So I can present some of my thoughts on dealing with a hemo abdomen now. If you've got a canine hemo abdomen.
I think it's helpful to bear in mind that it's likely to come from one of three places, that is the spleen, the liver, or the retroperitoneal space. There's a bit of a difference between small dogs and large dogs. Small dogs get fewer splenic bleeds and more hepatic and retroperitoneal breeds than dogs over 20 kg, but it's still these three locations in well over 80% of hemoabdomens.
If you look at the diagnosis of the thing that is bleeding in these locations, then the grey one, this one is the biggest. And if you look at the key, it's hemangiosarcoma, surprise, surprise. But if you look at the others, for example, the black ones or the lighter grey ones, these are too numerous to ignore.
And these are often benign lesions or other malignancies. Let's consider for a second what they could be. So we've got hemangiosarcoma, of course, but other differentials include benign things that are put in green here.
Or other malignancies that are put in yellow here. And I think it's important to differentiate the hemangiocart from other malignancies because the other malignancies may be much easier to treat and have a much better prognosis. For example, where you have primary lymphoma of the spleen.
Now that's not a normal multicentric case, that's a lymphoma just localised the spleen. These dogs were treated with splenectomy only and had a one year survival of 60%. Chemotherapy made no difference to these.
These dogs had other non-hummangiosarcomas. And the grading system that we use for other soft tissue sarcomas can be successfully applied, and the grade one tumours were cured with splenectomy. And the grade 21 still had survival in the order of 18 months, and it's only the high grade ones had survival comparable to hermanos.
And if you have histiocytic sarcoma, which is a horrible diagnosis in a lot of cases, but if it is localised to the spleen. Then you can often get a very long outcome for these as well. We've got a survival in the order of what's 1314, 15 months, treated with splenectomy, and the majority had an oral lowustine every 3 weeks afterwards.
So, although plenty of options are available, the hemangiosarcoma is outstanding in how aggressive it is. And if we're gonna make bold decisions in the prep room in our dog with a hemoabdomen, we want to be as sure as we can, we have or haven't got a hemangiosarcoma. Other diagnosis, in other words, may not be quite as bad.
So if we've got that dog with the splenic mass. How can we work out what that splenic mass is likely to be? A well described predictor of what a splenic mass is is the 2 2/3 rule, and you may well be familiar with it.
2/3 of splenic masses are malignant. And of those malignancies, 2/3 of these are hemangiosarcoma, so it's about 44% of splenic masses. Now, something that very powerfully changes this is the occurrence of hemoabdomen, OK?
If you've got a hemoabdomen, the proportion of humanangiosarc shifts to approximately 2/3. And so this is another quite well publicised descriptor of what a splenic mass is in the event of hemoabdomen. This is a study that I did a couple of years ago, and actually we found a higher proportion.
We found nearer 80% of hemoabdomen cases had a hemangiosarcoma. But we've got to be careful with this because no study is wrong and no study is right. It depends heavily on the population of dogs that you see.
And this study was done at an emergency centre, the RBC, and it also had quite a high proportion of German shepherd dogs. I'll come back to that in a minute. So We know the 2/3 rule, and we know that if we've got a hemo abdomen, we could call it the triple 2/3 rule if you want.
Other things that can tell you whether you've got a malignant process or non-malignant process would start with a finding of metastatic disease. And I don't, I don't think that that needs much elaboration on if you've got a chest full of mets, you know, you've got an aggressive cancer. But if you haven't got a chest full of nets.
And the splenic mass is huge, then it is suggestive, suggestive of a more benign process or a more low grade malignancy, and that may be a useful finding. The dog's breed, I think could be a tremendously useful finding, but this hasn't been well characterised so far. Let me ask you a question.
We've got dog A and dog B. Which one of these guys do you think is most likely to have a splenic hemangiosarcoma? Put it another way, if they've both got splenic masses, who do you think is more likely to have the Hiangosar, who's more likely to have something else.
Now, I can't see what you guys are thinking, but I bet the majority of us are thinking dog A. Possibly all of us, I think in dog A. And I think as a profession, we have a tremendous suspicion that German shepherds are predisposed to hemanic sarcomas.
And in fact, the first report of the predisposition to this disease I can find it in the vet record in 1978, where a group of practitioners wrote in and suggested that they think German shepherds are predisposed. Why isn't this borne out in the studies? Well, I think this is due to the the maths of it basically.
There are lots and lots of breeds. And in a study, you'll have lots and lots of breeds. It's not uncommon for a big study to have 60 or 70 different dog breeds.
And so if you want to compare this statistically, you'll end up with lots and lots of little groups with small numbers of dogs in it. And mathematically, that's a very weak thing to compare. And you often not get, you often end up with no significance.
Doesn't mean there isn't any significance. It's just a, a limitation of statistics in small numbers of dogs in lots of lots of groups. So we need to combine the dogs somehow to group them in some way, and people have shown that body weight can be useful.
As a proxy for breed or breed group, you know, dogs with larger body weights are more likely to get himang yourself. I mean splenic weight or body weight for breed. But in the study that I did, we sought to combine dogs another way according to their family tree.
We took these 5 branches of the canine family tree as representing the vast majority of dogs in our study of about 300 dogs, and we found that if a German shepherd dog or related dog like a Doberman has a splenic mass, 75% chance it's a heangi. On the contrary, if you had a spaniel or poodle, dx and beagle group, it's about 18%. Terriers or brachycephalic dogs, about 16%.
And your sighthounds, collies, retrievers and your mountain breeds are in the middle. So my second key point, unfortunately, without pathology, we, we don't know what this splenic mass is in our dog. But we can refine the 2 2/3 rule by using a occurrence of hemoabdomen, association with distant metastatic disease, finding of a huge mass with no metastatic disease, and the breed group per the dog's family tree.
Before I move on, I don't want to ignore our little feline friends, because these guys can get hemangiosarcoma and these guys can get spontaneous hemoabdomen too, but it's much less common. So this, to my knowledge, is one of the only studies of chemo abdomen in cats. And in these 65 cats with spontaneous abdominal bleeding, we found that about half of them had the bleeding due to a cancer, and 60% of these were hemangiosarcs.
So we could say roughly 30% of feline spontaneous hemoabdomen is due to hemanoussars. But the most concerning thing about this study is that regardless of the cause of hemoabdomen and whether it's curable or not, 12% of these guys survived to discharge. So cats tolerate this very, very poorly.
Moving on. So we've got our dog in the prep room, we found a splenic mass and we found it bleeding. And this is what people say, isn't it?
Shall I X-ray his chest? Because if we X-ray his chest, we might see stuff like this. Or we might see a pericardial effusion, a bit like this.
The atrial hemangiosarcoma will co-occur with about 12.5 to 25% of dogs with a splenic hemangiosarcoma. So, I think it's a very valid thing and a very useful information gathering exercise to X-ray the chest of a dog with a splenic mass.
But what does it mean if you find metastasis? Is it no good? Is it worth treating?
What would you do? Just have a think. Well, I'm gonna share some examples of my cases with you now, and I'll show you what I think.
This is Mimi, lovely dog. She had a large rapidly growing mass behind her right scapula, and it's taken off at the referring vet's where it was a horrible bit of surgery. It was really, really bleeding, and she actually required a blood transfusion.
It was given a diagnosis of a subcutaneous hemangiosar by the pathologist, and by the time the vet was taking stitches out to his horror, he saw it was regrowing. Now Mimi was referred to me. You could see the mass there.
And when we did a CT scan, I'm afraid this is what we found. So Mimi has too many Mets to count. Now, this is one case where we were able to get a CT scan after one dose of doxorubicin chemotherapy.
Where have those mates gone? And I bet you're too busy looking at the lungs. That you've not noticed that the mass has just dissolved.
Let me see if I can play that again. See, if you look behind the right scapula, you won't see the mass now. So Mimi, as it happened, lived for 13 months and all this metastatic disease, dissolved, at least temporarily.
You always get weird cases, don't you? So I'll show you another one. This is Lance, who presented dyspneic with a chest full of fluid.
The fluid was blood. We saw this And we treated him medically. I should say rather we saw this with a fluid full of blood.
This was due to a media sign on mass. The mass wasn't resectable, so we treated it medically and after 3 months, the mass had reduced in size, the effusion had stopped and it was quite discreet. So we then removed it surgically.
This guy lived for 18 months. And this is Dave, a splenic hemangiosarcoma case and his chest looked like this. And after chemotherapy it looked like that.
And this is Taylor, whose chests looked like this, and after chemo look like that. And this is Lizzie. We've got some beautiful images of her osteus hemangiosarcoma here.
And at diagnosis, we saw some metastatic lesions like this in her chest. And they went with chemotherapy. I'm afraid we can't do anything for the leg that had to be amputated.
Another splendid case here with lots and lots of little nets in the chest. And they went We see, as we CT dogs, we find that more and more of them have small nets in the muscles, which may be clinically silent, but it's easy to see on CT. And these go as you treat them with chemotherapy.
And there's this horrible angry lesion here on the left, and after just one dose of doxorubicin, it's dissolved, and another one in the jaw here, which is gone after one chemotherapy dose. So if that's surprising, I don't blame you because the books will say things like, and I'm quoting here from the current edition of the very well respected textbook. When advanced metastatic disease is present, the prognosis is unsurprisingly poor to grave.
Although occasional responses to therapy have been observed. And this ladies and gentlemen, is the danger of dogma and tradition led medicine. Because if the board certified res respected specialists who wrote this chapter had done a literature search, they would have found papers like this.
OK. Response to treatment is not occasional, it's 86%. And they also showed in this paper that the dogs who had prominent metastatic disease everywhere had exactly the same prognosis as those who didn't have metastatic disease.
If you want to see the survival curve, it's here, and it doesn't take a genius to see that these two curves for those with mets and those without METs is pretty much the same. So I want to tell you that hemangiosarcoma is a medical disease. Surgery is essential in a lot of cases to remove a ticking time bomb, like a spleen that's ruptured or is about to rupture.
But that's really a first aid measure or to confirm a diagnosis. OK. The, in a lot of the visceral cases or the muscular cases, certainly, you either see the mets or you don't see the mets, they're still there, and they are very responsive to chemotherapy.
Now let's talk a bit about why this could be. OK. When we talk about cancer being a blood vessel disease, that's not quite true, actually.
I was lying to you earlier. It's a cancer of the blood vessel precursor cells, the endothelial precursor cells. And these are produced by the bone marrow and they circulate, ready to get co-opted into a blood vessel, OK?
So the cancerous change occurs in a bone marrow, this is a bone marrow or a systemic disease. It's not something that occurs out in the periphery. And that might challenge our view on saying something is actually metastatic.
If we see a splenic mass with also a right atrial mass, is one the net to the other, or are they just co-locations of a systemic disease? And the systemic nature. Might give you a suggestion as to why it is quite chemo sensitive.
Hemangiosarcoma is a systemic disease with multiple foci, 80 to 90% respond to chemo, but in the cases of the splenic or visceral disease, I'm afraid, disease becomes resistant, comes back at you, and ultimately, you only have a survival of about 5 to 6 months. Does that remind you anything though? What about a T cell lymphoma?
Because that's also a systemic disease with multiple foci. That has a similar response to chemo. And a very similar survival.
So we're very good as a profession at recommending chemo for the lymphoma case. We're really not very good at recommending chemo for the Hemangiosart case, but actually the prognosis and the treatment is, is very similar. To understand further hemangiosarcoma and what you may be getting into if you treat these guys, we need to talk a bit about the perineoplastic the the disease that will be present to some extent in pretty much all the visceral cases and a lot of the big muscular and subcutaneous cases, OK?
We've got a histohoto over on the right, and I put that there to show you just how fragile these blood vessels are. And they're very badly formed and when blood flows through them, they can break spontaneously just due to the wear and tear of blood flowing through the vessels. So we kind of know that you can get catastrophic bleeds.
But you can also get lots and lots of little microscopic bleeds as well, which make the dog a bit anaemic and cause a bit of inflammation and drag the dog down, and they're less spectacular and less hard to pick up. You can also get fibrine deposition in the blood vessels, and that has the effect of dragging a clothesline across the vascular space, and so the red blood cells get smashed up. When they go through, and you can get microangiopathic anaemia as well as the haemorrhage.
And these are some shear injury products we see with the microangiopathic anaemia, and that can be a useful diagnostic clue as well. A second issue that we face, particularly if you want to take these guys to surgery, is that a lot of them have issues with blood clotting. This is Rudolph Verchoff, a very clever man, and he was the one who outlined Verchoff's triad of the three ingredients you have to have for a blood clot to form.
You need stasis of blood flow. Well, we've kind of got that in a hemangiosarcoma, haven't we, because you have lots of blind ending blood vessels. You need endothelial injury.
We've got that too, because the force of the blood damages the lining of these badly formed blood vessels. And then you need hypercoagulability. And let me tell you something else that's quite interesting is that pretty much all systemic cancers will make the animal hypercoagulable.
That's a feature not just of pumangiosarcomas. One of the theories behind that is that an embolus, metastatic cancer cells in the bloodstream will attract a cloak of platelets around it to protect it from the immune system and help to nourish it. OK?
So all cancers are hypercoagulable, that's the bottom line. And because of the other two things which are unique to hemangiosarcoma, we have a strong risk of aberrant blood clots forming. And we don't often get a problem with, thromboembolism things.
We find that there's lots of little blood clots that have gone unnoticed and subclinical, and it's used up the dog's platelets. Ladies and gentlemen, 75% of splenic hemangiosarcoma cases are thrombocytopenic. And 50% of splenicamangiosarcoma cases have also used up their clotting factors.
And with low platelets, low clotting factors, that fits the criteria for consumptive DIC. And then you can get immune-mediated diseases. Our cancers do what they want.
They're not under the control of any other part of the body. So you get cancer cells expressing antigens that just shouldn't be expressed and the immune system hasn't seen. And that can lead to aberrant immune responses where normal parts of the body get caught in the crossfire because they share similarity with this weird new antigen, the cancer's showing.
And some good examples, common examples in hemangiosarcoma include IMHA or IMTP and also vasculitis, which is quite hard to diagnose. But it does mean why a lot of hemangiosarcoma cases have got poor blood pressure and poor circulation to the extremities. And finally, if you've got a big mass of tumour, particularly hemangiosarcoma, which just grow and grow and grow, and bits of it end up hypoxic and die off and start to rot.
And that can cause the dog to have a fever for no good reason, and release a lot of inflammatory cytokines. So my next key point then. Is that where hemangiosarcoma remains in situ, you've got to bear in mind a strong likelihood of perineoplastic disease.
You've got the anaemia, either hemorrhagic or microangiopathic. Consumption of things involved in blood clotting. Vasculitis, immune-mediated disease, systemic inflammation and fever.
And I think we can already see that a lot of these things would compromise the safety of general anaesthesia, for example, The likelihood to bleed without clotting or difficulties maintaining blood pressure with a vasculitis. However, if you're treating one of these guys with chemotherapy, bear in mind that it's not all of the cases where the disease shrinks down to nothing. Some of them.
Dogs benefit, but the disease just shrinks down a bit. And in those cases, you could still have things like immune-mediated disease and vasculitis and thrombocytopenia going on because you've just got some cancer cells you seem not to be able to get rid of. And that can make the dog not return to his or her normal healthiness.
And it can also make them more fragile, if you like, more likely to get side effects of chemo. It may muddy the water if say you're treating a dog with chemo and it's doing OK, it could be better, it could be worse, but you start to see things like anaemia or thrombocytopenia, and you worry is that due to the chemo, or is it due to not enough chemo and the disease not being adequately treated? OK.
Now, just have a drink and we'll talk about hemangiosarcoma treatment. So I'll reiterate then, this isn't a surgical disease. Surgery is to stabilise and get a diagnosis only in the visceral cases where you have bleeding or you have something that's about to bleed.
And if we just do surgery for a splenic or visceral hemangiosar, you get survival in the order of 50 or 60 days. Now, around 1/8 or a 25, 8 to 25% of splenic cases will also involve a lesion in the right atrium. So imaging of the heart is indicated in a very useful thing to do, particularly if you have a small lesion and pericardial effusion, that could put the dog into shock at a later date, even if it's coming under control in other parts of the body with chemotherapy.
So, diagnosis, I routinely try to screen these guys for right atrial lesions. As you can see, another image of it here, right atrial mass, also there. And these can be removed.
I know it's an awful lot to do and it can get quite expensive, but I understand that a lot of these right ricular lesions are on the right ricular appendage, and they can be removed in an easier fashion to open heart surgery. You can just clamp across the little stalk and remove these things, with a good degree of success. So I'm not a surgeon myself, but I understand that's the way for a lot of these things that removal of them is reasonably straightforward.
I'd look at other ticking time bombs as well if you've diagnosed a muscular hemangiosarcoma, I might check out spleen and liver and make sure there's no lesions prone to bleeding there. But after we've done that, I would talk to the owner about chemotherapy. And, and the mainstay of chemotherapy for this disease is a doxorubicin-based protocol.
Before I start chemo, I talk about the adverse effects of chemo in general, it can upset the tummy. Or it can suppress the bone marrow. Doxorubicin can also be cardiotoxic, but that's typically a cumulative thing.
And after at least 8 doses, we often we stop at 6, but it's possible. If you're using sterile, if you're using cyclophosphamide, it has a risk of sterile hemorrhagic cystitis. And that's not a Obviously threatening side effects, but it can be really, really painful.
So I have a good frank discussion with the owners before we start any chemo, make sure they're happy with it, and sometimes they say, actually, no, I'm not comfortable with these adverse effects, and I say that's fine. But if you're not comfortable with the adverse effects of chemo, you do need to make sure you're comfortable with the adverse effects of no chemo, which is further bleeding, often within a week, a few weeks or a couple of months. And rapid death.
Sadly, we need to be very frank with people that they're kind of stuck between a rock and a hard place. But my personal opinion is that the benefits of chemo far outweigh the risks they pose. Most cases can be managed without any adverse effect or without significant adverse effect.
So this is the simplest protocol involving doxorubicin injections every 2 weeks. Go for 6 cycles and then stop. And if you do that, you turn a survival from about 6 weeks to about 6 months.
The protocol I use the most in the non-metastatic cases would involve doxorubicin every 3 weeks. And to keep the protocol intense and keep the pressure on the cancer whilst using a 3-weekly injection regime, I give oral cyclophosphamide in the middle. And that's associated with a similar survival time.
The most intense protocol, or one of the most intense protocols we can offer is the VAC protocol where you put Vincristine injections weekly in between the doxos and cyclophosphamide orally every other day at home. And that's still been shown to get a survival of about 6 months. But this is one of the ones that's been shown to correct the fulminent metastatic disease.
So in other words, you'll get the 6 months whether you've got obvious fulminant metastatic disease or whether you haven't. Understandably, a lot of people may not want to go for that. A lot of people may not want, may not be able to afford it.
There's a lot of dogs out there who are very nervous and we don't want to keep seeing them for injectable treatments. So a less intensive treatment is possible. Metronomic chemotherapy involving daily cyclophosphamide at home along with a non-steroidal drug has been shown in a small number of dogs to produce identical survival of about 6 months in the cases which are not metastatic at diagnosis.
It's not without risk, and 15 to 20% of dogs will develop sterile hemorrhagic cystitis. And if you've not seen sterile cystitis before, I can describe it to you. Imagine a dog who has cystitis, and they're really uncomfortable.
They're bothering the owner to go out and wee every 10 minutes and all through the night as well, but you give them antibiotics and that behaviour stops within a day or so. Can we all liken to that? Well, I can explain sterile hemorrhagic cystitis as that same really, really strong urgency to urinate and extremely distractingly sore bladder.
But it doesn't stop with antibiotics. And it can take weeks to get better. So it's a, not a life threatening side effect, but I hope I've shown you that it's not to be dismissed.
Now metronomic chemotherapy. Alters the tumor's environment, basically. It doesn't kill cancer cells.
That's very, very important to remember. So it stops the cancer requiring a blood supply or building its blood supply so it can't grow. It makes the immune system more hostile to the growth of the cancer as well.
So if you've got a huge burden of metastatic disease, the best metronomic chemotherapy could do is keep it at a huge burden of metastatic disease and stop it growing. It's not gonna bust this down to nothing. And so if you've got a metastatic cancer, I wouldn't offer metronomic chemotherapy, especially if you've got, a lot of perineoplastic effects going on.
I think for those ones, I would prefer the doxorubicin-based protocols which could bust the disease burden down. But if we're doing this, it is reasonably cheap, it's easy to do, and we don't need to use peroxicam. The initial studies use that, but now we've got evidence to support the use of coccibs or meloxicam as well, and that's licence and it's associated with much less non-steroidal effects.
If you want to use this, you can get small doses of cyclophosphamide ready for oral administration from places like Nova Labs or Kimopets. But are there other options? Yes, there are.
This study used a repurposed drug. Now thalidomide, if you're unsure, has a toxic reputation. In the 1950s, this was given to pregnant women who suffered from extreme nausea during pregnancy, and it treated that quite well.
But it also caused devastating loss of pregnancies and birth defects in a high proportion of their children. And because of that, it was banished for years and people didn't want to use it. But now we've worked out why that was happening.
The reason why it was causing such horrible, terrible side effects is because it is a very potent antiangiogenic agent. And so these guys very sensibly, wondered whether you could use a potent antiangiogenic drug to stop a cancer that develops from blood vessels. And they found similar survival times to doxorubicin-based chemotherapy, 6 months, in other words.
Now thalidomide, is an expensive drug, but we certainly can get it in the UK. It's no safer or no more dangerous the metronomic chemotherapy to use, but it's another, another tool we have in a toolbox. And this is an interesting study using a polysaccharide that's been isolated from the Coriolis versicular mushroom.
It's called I'munity, and it can be ordered online. And this study was done in dogs where the owners had refused chemotherapy. And they, and at the dose which is licenced, they found the time to progression of disease was significantly extended compared to the lower doses.
So, It doesn't work miracles, but it's something else that can be considered. Bear in mind the weakness of this study, you only have 5 dogs in each of these groups. None of these had chemo though.
There's been interest in a lot of cancers in developing an autologous cancer vaccine, where you take a bit of the tumour, you mash it up and you suspend it in something, and then you inject it back into the animal. And in this study, they found with the autologous cancer vaccine, a similar survival to doxorubicin-based chemotherapy. I'm not aware of that being commercially available though.
You've got another immunotherapy technique here with doxorubicin at a low dose. And again, you had a survival of a bit less, probably more like 4 months here, but of note, it is very, very variable. Some of them are going up to about 14 months.
So with the treatment of hemangiosarcomas, bear in mind it's a medical disease and we just use surgery as first aid and to confirm the diagnosis. At diagnosis, I'd recommend looking for other lesions which may rupture and causing further haemorrhage, and surgery would be indicated for these two before chemo starts. I think, yeah, but it gets very expensive and it gets very involved and it involves lots of procedures there and I totally get that.
But a few years ago, a very wise vets once said that we should not be judged on the treatment or the investigation we end up doing. We should be judged on what we offer. And it doesn't cost us anything to offer the gold standard and to make sure the owner understands all of that.
The mainstay of treatment for the systemic effects of your angiosarcoma is the doxorubicin-based protocol. In your non-metastatic cases that have had surgery, you could consider metronomic chemotherapy or thalidomide as an alternative, and the Coriolis ciar extract may have benefit as a supportive treatment. Have you thought About the whole philosophy of what we're doing there.
If we get one of the most aggressive cancers ever, let alone in veterinary medicine. We treat it and we often get it under good control with 6 or 4 doses of chemotherapy. We're doing very nicely.
And then we just kind of stop. Throw in a towel and wait till the dog dies. Essentially, we let the cancer win.
Just giving, we're treating an incurable disease that we'll win eventually and doing quite well and then giving up. Does that, does that kind of make sense? But, so, I can understand why we do that and forgive me for sounding flippant.
We don't want to keep giving chemotherapy to dogs. The side effects might start overtaking the benefits of it as drug resistance develops. But there is considerable interest in busting down the cancer to a minimum with a doxorubicin-based protocol, and then trying to maintain that.
And so a lot of us for a number of years, we're using metronomic chemotherapy after a doxorubicin-based protocol finished. And in this study here, you've got two very different survival curves between Group 1 and group 2. And you see the group one which had the maximum tolerated dose chemotherapy MTDC, and then metronomic chemotherapy.
And a much better survival in group 2, which was just maximum tolerated dose chemo alone. And for this, for the metronomic chemotherapy, they were using meloxicam usually with cyclophosphamide and also thalidomide, which can be combined with metronomic chemo if you want. Another study though has shown survival curves that are almost identical.
This one, I must say, didn't use thalidomide, as well as metronomic chemotherapy. So the jury's out because these two studies are both retrospective and they're not adequately powered to be able to make confident decisions in how we should treat these. What we can take from these is that the response is variable, but overall, the more treatment that you give, the more you're hedging your bets that your dog will have a good response or a better, as, as good as it can be.
I quickly show you a study here where they used palladia to serenim after doxorubicin-based chemo for splenic hemangiosarcoma, and there's no statistical benefits. So we're working on it, but currently we haven't got any strong recommendations to make in that regard. I guess each case is taken on a case by case basis and discussion with the owner, and their budgets, and their understanding, their attitude to risk, their desire to do as much as they can.
But some things which are worth considering as supportive care, particularly for those that have metastatic disease or those with disease in situ. Would be tranexamic acid. Which strengthens blood clots, in other words, pentoxyphalin.
As a treatment for vasculitis. And importantly, analgesia and gastropro protection. A lot of these guys with vasculitis and thrombocytopenia and things, their gut suffers.
They're not going to have the same ability to maintain blood flow in their gastrointestinal mucosa as a perfectly healthy dog. So gastrop protection, is really important and analgesia, you can imagine protection against little bleeds that may occur in the muscles and things. And Yan bio, a Chinese herb, is an interesting drug.
It has a similar effect to tranexamic acid. It can strengthen blood clots and if you've got a dog with a bleeding tendency, it's something to consider. There is actually a publication that shows in a test tube, and bio, will decrease the proliferation of humanangiosar cell lines.
But that's not in vivo. So, I've talked, I was talking generally and mainly about the visceral cases, because after all, they're the most common. And the prognosis for the splenic cases is about 5 to 7 months survival with treatment.
About 10% will go over a year. Survival remains very variable although some of them might crash and burn at 3 months, others might go kind of 1314 months. What I will say though, is that most owners would pursue this treatment again with another dog, even if they only got 4 or 5 months.
The retroperitoneal hemangiosarcs are rarer. There is a report of a poor prognosis of these, but I think that's probably the CT scan shows, due to the difficulty in removing these. Splenectomy is a reasonably straightforward process.
Removing one of these that has eaten into the musculature is, is often quite hairy and may not be possible. So it's probably in this study they had a poorer prognosis because it was just not possible to control a local disease adequately. Where you can control the local disease adequately, in my experience, they tend to do similarly to other splenic hepatic mangissars.
And then you've got the subcutaneous. Himania socks. And this is where the literature is a bit confused.
And possibly I'm confused too. You can see a very different survival curve here for the red subcutaneous ones compared to the splenic ones. The subcutaneous ones do better in the study.
OK. In one study, they even had a median survival of 3 years. The subcat ones, but 9 months for the intramuscular ones.
In another study, however, we found an average survival of about 6 months for whether they're subcuts or whether they're intramuscular. And that made no difference. So the way I approach the subcut ones, the intramuscular ones is that Very similar to the visceral cases.
I'd look at staging and I'd look at trying to achieve complete local control, which might be surgery. Amputation of the leg might be the most pragmatic in this dog, or a big surgery for this dog. If surgery is not possible, radiation could still be helpful.
And after we've controlled these, I would talk about chemo, and I would counsel the owner in a similar way to a visceral hemangiosarc. You know, we may not get more than 5 to 7 months here on average with chemo as well as the surgery. Cardiac hemangiosarcoma, most studies showed that it is more life-limiting with a prognosis in the order of 1 to 4 months.
But again, I don't think the disease is biologically any different here. It's just because of its location and the propensity to cause pericardial effusion or catastrophic rupture of the right atrium that limits us. If you're able to remove these and treat with chemo, or do pericardectomy to stop pericardial effusion occurring, I would think cautiously, we could get, you know, 5 to 7 months just like the splenic cases.
Dermal ones looking like these blood blisters up here and things. These things can be much more rosy, OK. If you find on histology that it's completely excised and that the basement membrane has not been penetrated, we can expect to cure these.
The aetiology of these is strongly linked to UV light exposure. And so we don't often see them in the UK, but in much warmer climes, they're much more common, I understand. And also in California, I'm being reliably informed that a lot of the local vets will just cryosurgery these things off without staging the dogs because they're common and it's very rare for them to cause any metastatic trouble.
So the median survival has been reported is about 3 years, even though about 80% of them ultimately recur, because they're very, invasive. However, the metastatic rate is low, about 1/3 of them metastasize. Things that could point to a better prognosis include being on the ventrum of the dog, being associated with solar-induced changes, and not having any subcutaneous invasion.
And then we've got the rare hemangiosarcomas that haven't been, very numerous in our literature, but there's a bit of information. The lingual Hiangiosars treated with surgery, plus minus chemotherapy, have been shown to have a survival of about 18 months, and around about half of them metastasize. There are reports of a couple of rare, nasal hemangiosarcomas.
I've seen one of these myself, and they can respond to either complete surgical excision or something at the front of the nose, or radiation therapy, and they can do very, very well actually. So, I think this is my last key point. Surgery and chemotherapy will be indicated in the vast majority of hemangiosarcomas that we see.
In the visceral cases, the surgery is just a first aid measure or to prevent something rupturing. And in the muscular hemangiosars and those of other cases, the surgery is to control the local disease, but it doesn't really control anything else. Chemotherapy is the mainstay of treatment because this is, a systemic cancer that has developed, from circulating cells.
It's a circulating disease, and the thing we need to treat that is chemo. Location affects the prognosis to a degree, but it doesn't really change the treatment, it just might change the expected benefit of that treatment. Sadly, all of these things are too aggressive.
But you can see exceptions in some of the lingual ones, a lot of the dermal ones, or the primary nasal hemangiosarcomas. And if you see anything weird, any unusual locations, people like me will always be very happy to discuss them. Before I go, I don't want to forget our feline friends.
I mentioned hemoabdomen earlier, so I'll tell you more about feline hemangiosars. We can get visceral ones that are very similar, as the canine ones. Highly metastatic, treated with splenectomy or hepatic lobectomy or removal of the mass, and then a doxorubicin-based protocol if possible.
More common though is the cutaneous or subcutaneous hemangiosars in cats. And these have a low rate of metastasis, but an incredibly high rate of recurrence. So please don't underestimate the amount of surgery you're gonna need to clear these if you ever see them.
In summary then, I hope I've shown you that hemangiosarcoma is a very treatable disease. It's a medical disease. Surgery is only first aid in visceral cases, but important for diagnosis.
And as I've said, in the intramuscular subcut cases, it's part of the local control of disease, doesn't really treat the systemic issue. Metastatic disease does not have to affect the prognosis, providing you treat it appropriately. Where, where, where disease remains in situ, that is either due to metastatic disease or, pre-surgical disease, beware of the paraineoplastic issues that you may face.
And please don't be scared of recommending doxorubicin-based protocols because for this disease, believe me, there is a clear, benefit in treatment that far outweighs the risk, any risk it could pose. And in terms of splenic masses, thinking back to our dog in the prep room. Remember that there's many benign and malignant differentials that exist.
Finding a metastatic disease is the only thing that's 100% sure of telling you a mass is malignant, but please also consider whether you've got mets, large size of mass in the absence of meths, female abdomen, or the dog's breed group. And I'm just going to end with this. This card came in this morning.
And I think, I used to think I got more thank you cards for treating hemangiosarcomas than anything else. But I don't think that's quite true. I think it's about aggressive diseases.
And the more, the more people will be more grateful as the disease becomes more aggressive. It's hard to, hard to think sometimes. But this card was sent to me in a dog, who we're treating for a retroperitoneal hemania sarcoma.
The dog's still with us and still on treatment. We've got the dog a few months so far and she's doing quite nicely, but the owner just sent a card to say thank you for, for all you're doing. And that's a common feature, as I say, with treatment of very, very aggressive cancers.
The more aggressive it is, the more grateful the people are. And I don't know exactly what goes on in the head of people in every case. But what I have thought Is that when people have a diagnosis of a very, very aggressive cancer in their pets, they hear things like, well, it looks really bad, so there's no point trying from all directions, from the internet, from their friends, from their colleagues, from their families, and there may be some sense or some pragmatism in what they hear, but it's still a very unfriendly thing to hear.
And they feel very isolated. And if we can turn that into, yes, I'm afraid it does look really bad, but we'll try as hard as we can. Then we're standing with them in the despair they face, and we're, we're helping them and they, and they feel not so alone.
And perhaps philosophically, that's why sometimes we get thank you cards when we feel we don't observe, we don't deserve them and haven't done very much. We, we've tried, you know. We've We've made the owner feel like everything that is being done that can be done.
Just a thought. I'd like to thank all these people who tolerate working with me every day. Massive thank you to the NHS and all key workers out there, people who develop vaccines, people who deliver the post, people who work in supermarkets, a huge heartfelt thank you from me.
Thanks ever so much to Bruce, Dawn, and the webinar vet team. It's been always a pleasure speaking for Webinar vets. I think this is the last one I'm doing this year, but I hope to be back next year for a couple of fixtures there.
Thank you ever so much to you guys too for coming or tuning in to listen. And if you've got any questions, I'll try my best to answer them now. Owen, that was absolutely fantastic, as always.
Really, grateful to you and thank you so much for your time and effort that you've put into tonight's presentation. I do really love your poster there, because that is something that we we hear so often, isn't it? But we've always done it that way.
Yeah, yeah. It's I must say it's a bit of a closet surgeon. You, you have successfully changed my mind in thinking that Emanio is a surgical disease.
So, if nothing else, that's, that's a, a good kudos for you. Good, good. I'm pleased.
Yeah, it's it's always hard to, to talk to owners about these things and give them hope with chemotherapy and, and be remain optimistic yet realistic that it's, it's not, you know, curing and everything else. You're just helping their baby get quality of life for, for longer. Hm.
Yeah, absolutely. Owen, you did such a good job that we haven't had any questions coming through. So, it's I think you, you, you've really covered everything, incredibly well.
And, once again, I honestly thank you for your time. And I'm sad to hear it's your last one this year, but, you know, two or three blinks in the eye and we'll be into 2022, and we can have you back again. Great, I look forward to it.
Folks, thank you for your time tonight. Thank you for attending. I hope you enjoyed that as much as I did and to Dawn, my controller in the background, as always, thank you for all your help and for making things run smoothly.
From myself until the next one, it's good night.