Great, thank you very much for joining me today. We're gonna be doing a bit of an overview of equine oncology, particularly focusing on sarcoids and melanomas as they're the ones that we most commonly have to deal with within the equine industry. There's a study now a few years ago, look at tumours within the UK, in, and just under 1000 cases were included in that study altogether, of which 24 were made 24% were made up of sarcoids, squamous cell carcinoma is about 19%, which there was a slight predilection towards mares and also cobs in that group, mares most likely due to the volar vaginal involvement.

Lymphomas made up about 14% of them, we start to go down into melanomas, gonado stromal, and mast cell tumours. What they found was that there was an increasing risk associated with an increasing age, which I guess is of no significant surprise. And I'll come on to some slight nuances in in that information in some more recent studies a bit later on in the talk.

And interestingly, in donkeys, 72% of all tumours that are reported with sarcoids, and I guess that the question is, is there bias in there that some of these tumours aren't being reported in donkeys rather than 72% of all tumours in donkeys, full stop, are sarcoids. I'm gonna go through my approach to the case in general to start with, and then I'm gonna go down into the more recent literature and what we can do with with those cases. When we look at a a pleasure, it's very easy in the growing world to look at something and just sort of say, OK, it is a it is a dilemma, let's not bother with the whole conversation.

But I think in not doing a detailed history, we really are doing a disservice to that horse because actually owners might elucidate that it's growing slowly, it's growing fast, there are multiple locations that they're aware of, or any of those little details that will actually make a big difference to the prognosis. Obviously you get your hands on these horses because because they say there's one human in a location doesn't mean there are multiple tumours throughout the horse, and obviously we are far more aware of the predilection sites that we get with these cases. Then do all your vital examinations, and I always like to map and record all sizes and locations of tumours so that we've got a, a record of what has happened and where we might be going as the years progress.

Any any further testing, haematology, biochemistry urin analysis, imaging multiple different formats there and also biopsy. So, when we do mapping, I like to use this as an example, and this is what I use, pretty simple. Lots of people have them, it's just off the, same as the vetting, sorry, the, passport one.

But it gives us a nice little diagram of where to put things. I then normally do a far more detailed diagram, particularly when it comes to melanomas, regarding the anus and tail, because I think it's important. I always use callipers.

I know it's not perfect, but it gives us the best chance of mapping the size of those. When we talk about biopsy and a bit later on again, I'm going to talk about biopsy to biopsy or not to biopsy, but it's important when we're talking about the technique alone, that the technique, sorry, the centre of the tumour may be necrotic. So let's make sure that we always get the edge, and if we get the centre as well, it's not a problem, but make sure we get some nice normal tissue as much as possible.

Got lots of options, true cut, wedge, complete excision, punch, just depends on the location, and that's a case by case decision. The bigger the better. FNAs are pretty much useless in all cases, so I just wouldn't even bother trying with those, for the vast majority.

Obviously correct handling is essential, so getting it into formalin, making sure it's cut if it's a large piece, label margins if that's appropriate. Also, when you're taking biopsies, particularly, say, punch biopsies, it's important to not use raptooth forceps or forceps in general to, hold on to the tissue. Try and use a needle to poke it out and into the sample box so that you don't cause any crush artefact.

There's nothing more annoying than the pathologist sitting on the fence with a crush artefact. Try and give the histopathologist, pathologist appropriate history, otherwise they're not gonna be able to really give you the full answer that you want, so make sure that you get as much as you can. And if you are doing an excisional biopsy.

If you're worried about a sarcoid, try and go 1 centimetre beyond if for most other tumours 5 millimetres, and then they'll be able to give you a good idea of margins. Factor, what else can we be doing in this case, indirect testing. A really good study here just come out in 2022 that had a really good look at all of the different formats of indirect testing that we could possibly do in a horse, and there are lots that are used in other species, but actually at the moment in horses, it's all pretty unreliable.

In some acute, extreme cases, say, acute myeloid leukaemia, which is very uncommon, you'd see a lymphocytosis. You might see a pancytopenia in some that, again, an AML or a bone marrow disease that's causing a complete loss of white blood cells and red blood cells. Often there'll be a thrombocytopenia in there as well.

Biochemistry can give you a good overall picture, looking at organ function, but also maybe think about hypercalcemia, because if there is a hypercalcemia, then that could be a perineoplastic syndrome. Not very common seeing it once or twice in my career. Anti-malarian hormones, specifically for a granulosis cell tumour, urinalysis, if you think there's a urinary involvement.

But the important thing with all of these tests is that it probably isn't going to be the crux of your diagnosis, it's only going to add to the whole picture. And finally in this whole issue is thinking about your imaging case it's not just a a dermal disease, neoplasia, then you're gonna want to start doing a few more of these things. Ultragenography is really critical, really good for superficial lung lesions, so the, the picture on the right hand side shows a nice tumour, and also can be looked at the visceral organs of the, of the, of the abdomen.

Obviously for the chest, it's only gonna do superficial neoplasias, so it's well worth then doing radiography to look at any deeper tissues as well. One note is that because of the depth of the chest in the horse, it is very difficult to get really useful X-rays for small tumours. So care should be taken in over interpreting a negative X-ray.

We've been using CT a lot more recently to look at head and neck pathology and head and neck neoplasia. And it's very, it's fantastic for melanoma, so this picture on the, the right bottom is a melanoma within just by the neck, which is causing various problems. Galbainigraphy theoretically could be used for bone scan, for bone tumours, but I haven't yet seen a case where I've used it, but it's always good to know that it is a potential option.

And what we've been doing a lot more at Lip is that we've been looking at IV contrast, in CT images. So we've been giving high volumes of IV, of contrast IV, and the idea being that although it's not as useful as intraarterial, it's safe, it is easy, and it is relatively effective. And so this is a post-contrast acquisition, image from the CT recently done by myself and our imaging team.

And it highlighted that the mass within the eyelid and then also it was going onto the eye extended ventrally below the eye and all the way round towards the optic disc. We already probably knew that we were at risk of needing to do an accenteration rather than a nucleation in this case, but what this confirmed was that we really needed to, and also needed to be pretty aggressive in the surgery to ensure that that mass had not, would not progress. What we've also found with a lot of these ocular squamous cell carcinomas and some lymphomas is that the tumour may be small on the outside, but when we do these CTs, we suddenly find that the sinus, the brain is being affected.

And so whenever I'm presented with one of these, it isn't just a simple discrete lesion. I always recommend a CT now, so that we can actually have a full look and a full assessment before we start going down our treatment road. Ask you one of the questions that I would love to ask is whether we could be biopsying, there's been a lot of stuff that's gone out historically saying that we really should shouldn't be biopsying because these tumours will then become angry, they'll grow, they'll get worse.

I think there is pause for thought in that, as long as in the sense of, if you don't have a treatment option going forward, if the owner is not willing, then no, don't touch it because you might increase the rate of growth. If, on the other hand, surgical excision or a surgery or a chemotherapeutic or anything like that might be indicated, then biopsy is absolutely the right thing to do as a primary step. Not only is it gonna give you the diagnosis, it's also maybe gonna give you some preliters for reoccurrence.

There is, of course, another risk that you might see neoplastic cells locally and systemically. Thankfully it doesn't seem to happen so much in the equine world as it does in humans, but we should be handling this tissue with care and being sensible. So trying not to cut too much into normal tissue, dragging your scalpel blade through there.

If you're suturing it closed, make sure that you try not to drag through the neoplastic tissue into normal tissue. And always have a plan post biopsy. You may not have the exact plan, but make sure that you are going to do something with that information.

And also sometimes it stops unnecessary treatment. I've definitely biopsied things that I was certain were going to be a neoplastic process and have proved to be an inflammatory one requiring only systemic or local steroids. So sometimes it's in that advantage from that perspective.

So, really just only some important thoughts on when you consider treatment. Response is always going to be better the smaller the lesion. So early treatment is always better.

From that point of view, the wait and see approach, pretty much that, you know, benign neglect is not benign when the tumour is growing, potentially going to metastasize, although relatively uncommon in sarcoids and melanomas, and also become surgically non-resectable. What could benign in the nature of the neopla does not mean not fatal. You know, melanomas are considered benign in themselves in the equine population, yet they are often fatal due to their ability to lead to faecal inability to pass faeces or various other problems.

Ideally, it proven effective. Now the problem is, as we'll go through a lot of this data, that's not really very easy within the equine world. And also those cases that we have got, they don't, sorry, the studies we do do have often don't have that many cases in, so we have to be careful with saying they're proven.

A lot of research is ongoing in the preparation of the number of papers that are out there is, is huge, particularly when we start talking about individual tumour types now rather than a big overview. And I said, I know is central to creating an appropriate treatment plan. I think most people who are going to be listening to this are fairly OK with sarcoids and the overview of them, and so I'm gonna keep these this to a couple of slides before we go on to the treatments of them.

It's an induced tumour of fibroblasts and. Seems to me that about 6% in one study in 2018 showed that 46% of equine cutaneous neoplasias were sarcoids. So it's a real problem in the equine world and obviously they, they all carry different prognoses.

The owners, there is an owner reported prevalence of 5.8%, so 5.8% of horses out in the world have sarcoids as per owners.

There's a close close association with bovine papillomavirus 1 and 2, and there's so much work going on with that at the moment that I'm not really even gonna touch on it because that in itself will be multiple letters. And there seems to be an increased risk with thoroughbred called horses, arrows, and Apolluters, and also with age, so 70% of sarcoids is developing in 4 year olds and above. And it seems that it's not cash transfer, your house fly, is able to carry the bovine papillomavirus.

It's probably worth considering that in your ongoing air and cases to ensure that there is no significant fly burden. Anna Hollis did a really good review, this year, 2023, looking at sarcoids. So it's got a really nice rundown of all the treatment options, what's available, what's sensible.

So, if you, if you need that, then that's a really good nice little review. We're sensible to classify our sarcoids at the beginning of treatment because they all carry different prognoses and different treatments. So knowing these 6 different types of sarcoid will really help in that process.

So talking about biopsy and earlier I mentioned that I was gonna bring this up again, there were 2 studies this year, again, looking at whether or not a biopsy can predict the risk of recurrence. So this not only therefore leads you towards a biopsy saying, OK, it's gonna give you a diagnosis. Probably we're all fairly aware of what a sarcoid looks like, but always worth checking.

But also it's gonna tell you, is there an increased risk of recurrence? So if we skip to the bottom, sorry it's a slightly wordy slide, but if we skip to the bottom three lines, this was Kerno rather than the Carraous study. And what they found was that superficial inflammation within their biopsies made it much less likely that there was going to be a recurrence.

But that 30 out of 64 sites following surgical treatment had recurrence, so 46.8% of cases have recurrence. And then 21 out of 64, so 32.8% of those horses had sarcoids at different locations following the surgery, so it's a significant concern, the fact that there's this much recurrence.

Carolas, and his crew, his, hers, sorry, not sure, crew further looked into the histopathology and whether there are histop histopathological cues that could tell us whether or not these cases are going to recur. They looked at mitotic count, cellularity, necrosis, nuclear pleomorphism and inflammation. And they found that the only thing that really predicted was mitotic count.

So the picture on the top is from their study and shows multiple mitotic figures, whereas the one on the bottom shows no mitotic figures. And they found that 80% of cases that had high mitotic count indexes, greater than 20 in a 2.37 millimetre squared section, were likely to occur, whereas 18% that were under 20 recurred.

They also found that fibroplastic were also more likely to recur 3 out of 4. And that was different to other types of, of sarcoid. So it could be really useful to have this information at your fingertips to be able to tell the owner, yes, your case has high mitotic count, therefore, it is likely to recur, we should therefore do extra things to either treat with chemotherapeutic agents or even consider just monitoring and therefore repeat surgery as and when it occurs.

Also another really good review of sarcoids by Of and the crew in this year as well. Now this was a study to look at a meta-analysis of all the papers that are out there on the treatment of sarcoids and trying to work out which treatments are appropriate and effective. But first of all, they had to work out which studies were useful.

And there are some like 1400 studies on sarcoids out there, of which 10 fulfilled the criteria of a systemic meta-analysis review. And the most common reason was that there was no histopathology, so sarcoids were just deemed sarcoids based on their appearance. And or they didn't have more than 6 months of follow up.

So both pretty significant faults in these studies. And I think as we go through the next set of slides, that has to play in your mind that all of those were not included in this study. There, there are ones where there are 15 horses, no histopathology, short term follow up.

What they found in this study was that radiotherapy, cryotherapy, intralesional cisplatin, and electro chemotherapy were the most successful of all treatments. But there is a slightly odd bias in this study that other techniques, sharp as in Malaysia, could be better than those things or as good, but because their studies lacked rigidity, they weren't included. So we have to take a little bit of a pinch of salt with this as well when we are deciding what to do, because I'm not recommending that every horse goes for radiotherapy rather than a sharp excision.

This is their data looking at horse regression er horse. Lack of recurrence and tumour lack of recurrence, and it's just, it goes through all the 10 studies, all the different treatments, and it's just quite a useful thing to have in your mind that particularly the, The radiotherapy is a bunch in the middle do very well, whereas some of your sort of more topicals on the right hand side of each graph are not doing quite so well. No surprise there, we know that they're not as good as some of the other things.

There's some slightly newer therapies before I go on to the more. Usuals that we use, and Anna Hollis is sort of probably one of the people who's pushing this the most, and she's really been, pioneering and and championing ongoing new treatments. So Stephonta, is a new drug out there that is primarily for mas in docks rather than anything to do with horses, but is a tumour agnostic, and what it does is it leads to a massive inflammatory response.

It brings in all sorts of white blood cells, but also what it does is it leads to an increased permeability of the, the blood vessels, and in doing so, they leak, they clot, and then they stop functioning. And as that occurs, that obviously also causes necrosis within the tumour as well as the inflammatory response that's causing necrosis. Overall, it causes hemorrhagic necrosis of the tumour, with relatively limited effect on the normal tissue surrounding it.

In it's very well tolerated, you can go quite high, but in horses in the pilot study by Ridder in 2020, they found that horses are far more sensitive to this. And if we do the higher doses within normal tissues, we see a lot more necrosis, than they were seeing in the small animal. So they've scaled the dose back and we've had some slight changes in the protocol compared to dogs, but it seems to be having a good good effect thanks to those slight alterations.

What they have found, both these guys and Anna and obviously people like us who are now using it as well, significant inflammation, bruising and necrosis, and that whole tissue can slough over the next sort of 6, 16 days. And Anna's got some fantastic pictures of, of big holes that were created by this. So we have to be aware of that when we're choosing location or concerns about that patient.

But all of them have filled in gradually and recovered well. Because of that massive information, there is a need for for extra medications at the same time, so steroids and non-steroidals. And it is actually currently being studied for squamous cell carcinomas as well, in, in horses and also for multiple other masses in humans and stocks.

So to use it, we measure the size of the tumour approximately using the this calculation that we set up, so it's tumour width, times length time depth and then times 0.5, and that's gonna give us the volume for rounding of the edges. And the dose in horses is 0.35 Migs per centimetre cube.

They came up with a maximum dose of milligrammes per horse for most tumours . But 0.2 milligrammes of mucuscutaneous ocular lesion, so they did a squamous cell carcinoma within the eyelid, and they kept it at much lower doses to try and reduce the risk of too much damage to the eyelid itself.

That said, it makes in at the time of injection and then non-steroids follow, and when giving it, it's through one injection site and then a fanning out of the medication throughout the tumour itself. I presented some stuff, a few years ago at Beaver, in which you treat 14 horses in 18 saos. I'm sure she's got more data since then, .

And 5 of those previously have been treated with other modalities, whether it's chemotherapeutic or something else. She did increase the maximum dose of 4 milligrammes if required based on tumour size, and didn't seem to worry too much about that. 5 horses, 6 sarcoids in total.

Required multiple treatments, and interestingly 5 of the 6 sarcoids have been given previous treatments, so were they slightly less sensitive to the medication for that reason. Three of the horses during treatment required due to the severity of inflammation, and 13 out of 16 of the darkoids are fully resolved. So obviously small numbers, but this is giving us an opportunity for ones that aren't surgically resectable.

So, it, it is a very useful adjunctive therapy or complete therapy in some of these cases. The RBC has been pushing and working on some different things as well, so electro chemotherapy has been around for quite a long time, the idea being that by stimulating you get increased absorption of the chemotherapeutic within the tissue, requiring less of the chemotherapeutic or make it more effective. The problem with electro chemotherapy is that it's always been based on cisplatin, so relatively dangerous as chemotherapy do go, but also because of the electrical impulse being quite strong, it's always required a general anaesthetic rather than being able to do it in standing.

The RBC and Mike Hewitson have been looking at this tumour specific electrocoration which has from their reports, been having quite good success. So they've been doing it since 2022. Haven't yet published on it, but are collecting data, so hopefully that will come out at some point soon.

And they've been doing it on those sarcoids that are not surgically approachable or have poor margins following a surgical resection. Also, they're using bleomycin rather than cisplatin, so it's far safer. With much fewer, human health risks, which is fantastic and makes it far more acceptable in most places.

The big difference with the TSE rather than the ECT the electro chemotherapy, is that it has this dynamic variability of pulse, so that the. It causes the poration of the tumour cells, so it allows more of the chemotherapeutics into those cells, but it's not causing the necrosis, the death of the red, of the blood vessels that was causing necrosis and pain associated with the ECT. So it stops necrosis, it's less painful and therefore doesn't seem to require general anaesthetic compared with, ECT, make it far more of an approachable and useful tool.

And as I say, they've shown promising results with sarcoids less effective for melanomas at the moment, in the short term they are looking, trying to look at the long term data for that. But I think this is something that really could play out quite well, especially for, for certain tumours, for certain types of sarcoid. What other options are out there because some of those are pretty nasty.

BCG is obviously something that's been around for quite a long time and actually has become more available again now since immunocydin's been brought out to the small animal world and we're able to get it on an SIC. So some studies, one in 2020 most recently showed a success rate of 52% to 69%. Custom was at the 52% mark.

What BCG does, the, the cell wall part of it, it induces apoptosis by releasing a lot of cytokines, makes a big immune response and also necrosis of the tumour cells themselves. Interestingly, it's unsuccessful and varicose are occult, but it's quite good at relatively good at periorbital sarcos often the worst ones. As I said, immunocyan is now available, it's relatively expensive, and you can use epinephrine concurrently with it to try and keep the immunocyin within the site.

But lots of people don't do that. The dose is just on there based on the study, by Caston, and what they do is 2/3 of the dose is given within the tumour itself, in a grid pattern, so where the, . The last ones, we've been given in a fanning pattern.

This we do grids, so multiple lines, across the tumour, and then one third of it underneath the tumour as well. And then you want to see that horse every 14 days, and decide whether or not it needs another medication. And if it does, then do another one.

Keep going until that tumor's gone unless after 4 there's been no improvement, in which case then we want to stop. So we see that picture is of a melanoma or I could find a laser picture for a sarcoid, but what. What I just said earlier is that surgery didn't actually come in as a high hitter in successful rate.

And I think that fits because of some of the studies not being histopathologically diagnosed. But when we look at some of them, you're looking at 73.5 to 80 something% success rate when we're talking about, CO2 laser, cryosurgery, excision, radiotherapy, or a combination of both, but.

There are multiple studies looking at all of those regions that region of 75, 85% success rate. Some claim higher, some claim lower. What they, some of them found again is that there is recurrence of the neoplasia with laser only, so about 38% of them, had recurrence.

So, although the surgeons may like to claim it is perfect, it is not. And so we just have to be careful and have to monitor that site carefully once the surgery has been done. So many creams on the market for everything, and some of them have been researched so it's good to just have a little bit of a thought about this.

Doesn't mean we shouldn't use them if they've got poor success rates, just means we have to use them with the caveat of understanding and the owners' understanding of that situation as well. So a Micro mod 5% can be applied 3 times weekly for until resolution, all the studies have gone up to 32 weeks. 60% of them had complete resolution, which isn't bad for something that is applied 3 times weekly.

And 80% had a 75% reduction in in size. Only 15 horses, 4 withdrawn, so you're only talking about 11 horses in that group. So care with that interpretation.

5FU twice daily application may work for a cult. The important thing with 5FU is it has very limited penetration of the tissue, so it's not going to work for your nodular, your larger swards, you're gonna have to keep it just for those occult ones where it's just superficial. Xoa showed you 60% recurrence with variable outcomes, so it's not one that I would be jumping up and down the reach for.

So the autologous vaccines that are available or theoretically available, they're. I worry about them from the point of view of efficacy and also safety and known treatment. So there's one study looking at 18 cases, 75% had a decrease in the size, in numbers, sorry, 94 had a decrease in size.

So it all looks pretty good, you know, this is a pretty good response, but. Small numbers and it's never really taken off, which always makes me think that it probably isn't quite as good as it claimed it was, and there are complications, inflammation, etc. In a lot of the cases.

I don't know if anyone's even doing Blood route anymore. I love the picture from their own website with somebody with no gloves on. Again, I would be avoiding Blood route.

The only study out there was a questionnaire based one rather than anything, robust and. 49 sarcoids had responded completely, 15 partially and 10 none. So, you know, all right pretty good results if we believe them.

Chemotherapeutics are probably one of other than surgical excision, one of the main things and we we've talked about TSE with bleomycin, which I think might be the way that things should be going for safety. Cisplatin has been something that's been used a lot and a lot of people are still using, but care should be taken when doing so. Any of these chemotherapeutics, when they're being sent out by post, we have to be careful about that.

If you're not wearing appropriate PPE and the owners aren't wearing appropriate PPE, it's a health and safety nightmare waiting to happen. And cisplatin, carboplatin, any of those are all chemotherapeutics. The care has to be done, taken when handling them.

There's a big study by Tao looking at about 630 tumours of varying types, and for sarcoids, he found a 93.3% overall cure rate at 4 years, so pretty good success rate. When you look at the systemic review, that study was sort of in the moderately OK at best, from, from that review perspective.

But it's the biggest one that is out there, so it's quite useful to have. They look at electro chemotherapy, it was about the same 92.3% success rate, and required the general anaesthesia, so didn't particularly add anything when we talk about cisplatin on its own.

When we do it, we do it with a bit of sesame oil and water so that it stays in situ for longer, and you're doing 4 injections every 2 weeks, and injecting the grid-like pattern. Big side effects, big amounts of tissue necrosis, hair loss, depigmentation, and as I said, health and safety concerns about using cisplatin, because there's some good studies from years ago where anyone handling it then had cisplatin in their urine, which is only going to increase their risk of either not responding to cisplatin when they need it, or having some degree of damage to their cells because of the cisplatin. There are a few novel novel in talking 56 years since they started being out there, a topical liposome well encapsulated bleomycin in combination, with a couple of other medications.

I had again about 70, 80% success rate at one year. And also 5% acyclovir. The problem with acyclovir is that sarcoids don't contain the kinase required for acyclovir activation, so there shouldn't be a reason it should work.

In the study, they found very little response, so I wouldn't be recommending acyclovir, whereas the topical liposomal might be an option. There was a review that Nottenbelt did in 2018, based on some of his work and found that again going to that 5 FU liar zone only and the desarin liar zone, there was a better outcome than, say, the one that each of those on their own. So that combination seems to have a better effect than monotherapy.

Perocular sarcoids are probably the most annoying, as we all know, of all the sarcoids to deal with, and treatments are becoming more and more limited for a number of reasons. So local low dose interstitial brachytherapy, so iridium wires or seeds, placed within the eyelid. I remember doing those as an intern, I'm not sure if anyone's actually still even doing them, .

Pretty good success rates, no surprise there you're sticking brachytherapy within the tumour for quite a long time. There was, and part of the reason is, is there's a high risk to human health, because, A, handling, and B, if they fall out, does the horse eat them? Do you pick them up in their bedding, etc.

So, Frustrating for the horse population it's never really taken off due to the human health considerations. High dose brachytherapy was showing excellent promise, frustrating with the animal health trust closure, it's pretty much stuck at that site at the moment because moving it is a nightmare and setting it up. I know Anna Hollis is again pushing to try and get that set up at Cambridge, but making the bunker required for it, is not the most simple, so it's a watch this space as to whether or not she can get that up and running again.

And cisplatin in that area had pretty low response rates, so we've been using a lot of BTD in that area, and selfonter as well to try and treat some of those. Radiotherapy is theoretically an option, but the problem is getting it. It's, it would be a lovely treatment option for these ones, but there is, I don't know if there is actually anywhere in the UK.

I don't think there is at this moment in time that is able to do radiotherapy. There is somewhere in Germany as far as I'm aware. So it's there for information rather than saying it's a treatment option that we should really be considering.

All the options for radiotherapy are strontium plestherapy, that's a strontium wand, problem with that is it's got quite low penetration, so it's really good for ocular, neoplasias, things like that where it's a relatively small area, very superficial, and we can really treat them quite well. And then all the rest, as I've said, are slightly, this is for information rather than treatment. Also radiotherapy in itself, this was when I was in America, has some significant side effects.

It's not benign, and it can cause skin erythema descrimation of the the skin, depigmentation and permanent epilation. Also when you start to look longer, if it's anywhere near the eye, cataracts, corneal ulceration, bone necrosis, fibrosis, so lots of stuff that can go on and because we're not doing it in high volumes of forces, the exact techniques and things like that aren't always understood. And this is a study that looked to 614 cases, sarcoids 230 cases, had a 75% success rate, and they found that, 87% of them were responsive to the excision.

But they had lots of treatment failures with intralesional platinum containing drugs, so cisplatin, carboplatin, cryosurgery, acyclovir, multiple sarcoids on one horse. So any of those things are gonna make things fail. And immuno stimulating treatments increases success, but, you know, this was everything they did and they still had 25% failure, in, on the average case.

That's sarcoids, the lot there that we can consider, a lot of different techniques, and a lot of different ways that we can try and treat these horses. There is no one answer, because every sarcoid is different location, type, etc. I haven't really included AW4 cream because it's a bit of an unknown.

It, it obviously works well, I'm not denying that fact, but exactly what's in it, the percentages, how they're all calculated. I struggle to bring that all together into a presentation format because it's just not available. That information isn't available.

Also, it, we know it carries heavy metals, it carries platinum-based drugs. So care has to be taken, it should never be left on the yard, etc. So.

Care when using it is what I would say it has its place. Nerves tumours I've just put in here very briefly because they can appear like sarcoids and have very different prognosis. So histopath histopathologically can look very similar, but they have very low risk of malignancy, .

And they're normally subcutaneous nodules that range from quite small to very large, and so you know, you could think that they were nodular sarcoids in some cases. Normally excision is completely curative, although sometimes they can be hard to remove completely because they can have little tendrils reaching out. And sometimes people will recommend intralesional chemotherapy, others will recommend nothing because monitoring just seems to, they don't progress in the same way as you would, occur.

But the risk of recurrence is there and can be quite high, so just care, monitor if we do get poor margins, then ideally intralesional chemotherapy, otherwise close monitoring. So the next big group of of tumour is the squamous cell carcinoma. Again, just like saroys are not gonna take a long time to talk about the look of them or anything like that, everyone knows what they look about look like.

Commonly affected areas, the external genitalia, whether it's the penis or the the vulva, we're seeing a lot of ocular ones at the moment, ocular and periocular, and, They're sorry, they're the main, main locations. Metastases do occur, so the, the slightly bloody picture at the top is evidence of large lymph nodes associated with a squamous cell carcinoma of the penis, which we had ultrasound scanned, located those and confirmed that this horse was going to also need the lymph nodes removing. In humans, there's only a 50% survival rate of head and neck squamous cell carcinomas currently, but hopefully it doesn't seem to metastasize in the same way in horses as it does in humans.

So fingers crossed we're gonna have a better EPS rate than that. There are some predilections that we see with squamous cell carcinoma, so Hafflingers have a predilection, particularly with limble's squamous cell carcinomas, although the last time I saw a Haflinger I don't remember, . There's also other breed predilections, Clydesdales, Belgians, Shires, Appaloosas or anything with a white eye really, or a white penis vagina is going to be at risk of squamous cell carcinoma.

And this year another study came out of Colorado, where they looked at 3,272 horses and what they were trying to work out is whether latitude, longitude, UV maximum values. Were associated with the occurrence of a squamous cell carcinoma. And what they found that the only one is the higher altitude was a risk factor.

And so what they proposed was that it is the overall amount of UV exposure over a long time that is the risk, rather than a one-off maximum intensity UV that may burn. Obviously, multiple burnings probably counts, builds up to that overall picture. So again, nothing of surprise, but it just builds a picture that we've got to be careful with these cases that are white.

In 2015, a group found that there are some prognostic markers, so expression of P53, with P53 within the tumours correlates with metastasis, and less differential tumours are increased risk of death for that horse. There's a smaller number that there seems to be this . Paillomavirus 2 that seems to be associated with a few of them, 6 out of 13 tumours had it, and not seen in solar damage cases.

So is there slight, are there diff nuances in this squamous cell carcinoma? Is there a virusy one versus a a solar damage one? Again, information rather than definitely guiding our treatment.

The squamous cell carcinomas are difficult to treat, there's no question about that. Surgical excision is our number one treatment option because most of the other things are not very effective and we have to therefore be careful. Theoretically, radiation therapy could be used, intralesional and systemic chemotherapeutics could be used, although have such poor success rates, there's really not much point in talking about carboplatin, doxorubicin.

You might use cisplatin as an adjunctive post surgery, but most of the time that's not even something that we consider. Photodynamic therapy, theoretically is out there again for information because I'm not sure of anyone doing photodynamic therapy. For the more minor lesion, we can do some topical treatments.

So 5 fluorouracil, 5 FU, can be applied into the lesion, intralesionally, every 2 to 5 weeks until tumour reduction is seen and or topically, which is far more common. So in the first intralesional they did 5 horses and they found there was a big reduction in the size of the tumours, but sadly recurrence occurred. So again, it might be an adjunctive thing to add in rather than the primary treatment, get rid of the tumour first.

Topically can be really helpful, especially in those early cases. So when you're talking about a vulva or a penis, which has the, the, the mild changes, the slightly ulcerated, slightly reddened looking regions, that's those ones that you can use 5FU. Again, I mentioned earlier that it's got really narrow penetration, it's only millimetres of penetration.

So anything deeper than that isn't going to be affected by 5FU. In Mas they applied it every 2 weeks, then, sorry, every day for 2 weeks, then every 2 weeks until remission. Sorry, 2 weeks on, 2 weeks off, 2 weeks on, 2 weeks off, that's what I was trying to say.

Males, they did it, every 14 days, just one application every 14 days because of difficulty in getting to the penis and willingness for the horse to allow it. 10 out of 11 of those animals were in remission, and as I say, these were all horses with mild lesions rather than significant lesions. MetaCam, there's a study out there looking at a case, so really not very helpful and I really wouldn't be using this as a treatment.

You could use it. As an adjunctive, putting it on metaam rather than bee, for example. Theory being that it stops angiogenesis, essential for growth, and can help in those cases.

But there's 5 months before recurrence, was there always going to be 5 months before reoccurrence, so don't know. Immunotherapy is a theoretical thing that's going on out there. Again, one case, I really wouldn't be too interested in that.

I can see those probably are one of the ones we use the most. A lot of people are using it intralegionally, but there isn't much evidence, for, sorry, I thought I had for regional, but it's something we could consider. We're using it a lot with our ocular ones, so we have a surgical debulkment, maybe removing the third eyelid.

And then mitomycin applied to the eye, at the time of surgery, and then every 6 hours for about 7 days with 7 days on, 7 days off. In some of the more mild ones we're going twice a day, because we've found that seems to be effective and slightly more approachable for at home cases. So the important thing about squamous cells, try and get rid of them, cut them out first and foremost, and then consider these little nuances in there.

Make sure that you're doing the imaging correctly because these are the cases where you've got that infiltration within the sinus, within the brain from an ocular squamous cell carcinoma. Feel for your lymph nodes, consider metastatic checks, so ultrasounds of the chest, the abdomen, X-rays, etc. Because I've definitely found some that have some pretty nasty abdomens.

Melanomas, the last big group that we're going to do, . Obviously associated with coke colour in the vast majority of cases, you do get melanomas within other colours which are different kettle of fish. About 80% of grey horses over the age of 15 will have melanomas somewhere, whether they're visible or not doesn't matter, they're somewhere in that horse.

We know what they are, we know that they're mostly around the tail, perianal genital region, but also around the lips, particularly the commercials of the lips, the salivary glands, and then internally, although, to be honest, so difficult to find on ultrasound scan. Although frequently benign, they are considered benign, some can metastasize, so always worth getting some histopathology when you do remove them. But more concerningly, it's their growth.

Doesn't appear to be a link with sun exposure, and there are now reports of a primary corneal malignant melanoma within the eye. This is a study 3 years ago, in 2000 looking at Camarty horses and just the location of where the melanomas are. And it doesn't really surprise us that this is their route.

Although I am surprised that parotid is relatively low, I would now, in my experience, put that quite a lot higher, but tail perianal being the most frequent location. We know associated with grey, therefore it's gonna be kinetic, but the guy at some, I've, I've forgotten the the study here, sorry, have shown that there is a gene associated with it, that causes grey and thus enhances the melantic proliferation. And this normally sort of progresses and gets worse by the ages of 4 to 8, and 4 to 8 years old, and then that every year they sort of progress by 4 or 8%.

So they're getting worse and worse, more and more of them. And locoregional malignancy is more likely a problem rather than the systemic malignancy. In most cases in this study, they found that melanomas progressed by about 0.3 of a grade.

This is the grading system that they put together, and it's quite useful to have. And so it's just a way of being able to say, OK, this is how bad things really are. Doesn't always change what we do, but it's useful to give to the owner, as and when you have that discussion.

Ocular melanomas are one thing I'm just gonna highlight specifically rather than anything else. And the reason for that is it's very important to find if it's a cyst or a melanoma, that's gonna really change your therapy and your recommendations to the owner. Common sense number one is what is the colour of the horse.

If it's brown, it's much less likely to be a melaloma, far more likely to be a cyst, but what you need to do is get an old car on there. If it's a cyst, you're gonna have this hypoechoic centre, as in the video that played and a circle, whereas a melanoma will have a solid tissue that you can see on the scan. What is what you're gonna recommend because obviously a cyst has a very different treatment to a melanoma.

Other imaging is pretty essential in these cases because because you found 11 place doesn't mean that you're not gonna find them somewhere else or how bad they might be. But I always recommend an upper airway endoscopy, and this is obviously a pouch and we can see these arrows pointing at melan melanitic cells, which might become a problem in the future, but they're not something I'd be worried about now. One of the, the problems with these cases when you find these, or if you find them unbeknownst to the ongoing disease, you're, you're worried about a fever of unknown origin, you find these, is what effect that's gonna have on the insurance.

So if it is documented down, I like to try and be as blunt as I can and say at this moment in time there is no evidence of a melanoma, there are these melanocitic cells, but this shouldn't hopefully stop them ensuring that what's going forward. As always looking for mass and radiography and CD to look at all of these things. If we worry about melanoma, benign neglect, that's what lots of people say.

And I'm very much against benign neglect in these cases like I am with sarcoids because, you know, that, that anus and that picture, if we'd started early, we might have been able to control them for another number of years, whether that's through surgery or onset or whatever it might be. We could have controlled that to a point where we at least maintained a normally functioning rectum. The middle two pictures are a horse that presented with a facial paralysis to me a little while ago and actually had a melanoma that was sort of going all the way through into the sinuses, and actually going into the brain.

So. This, you know, these melanomas, although infrequently they'll do this, we should be aware of it and we shouldn't ever underestimate a melanoma. Surgical removal is always my preferred option, because it's quick, easy, and gets it done.

Often though, that's not an option, whether it's in the parotid, it's deep to a bone, whatever it might be. Chemotherapeutics really aren't very effective. Cisplatin, mitomycin, electroche, chemotherapy, chemotherapy, they're really not very effective.

And lots of people are injectingitomycin C and maybe it might shrink it a little bit, but it's, it's just not effective. So What else can we do? So cisplatin, they found an 81% local cure rate, but you're talking about tumour being injected, and how many horses have you ever seen with one finger?

Platin continue needs at the free relapse again of that site, not of the multiple melanomas that are elsewhere in these waters. So, Again, another piece of research, sorry before I come on to the other ones, brain pause there, a group in 2020 looked at the bark of white birch and found that it affects primarily melanoma cells and fibroblasts, and it seemed to be anti-proliferative and cytotoxic. It also penetrates the skin well, so it could be used topically.

Now this is all research and I haven't seen anything come out of this group since then, which is a bit of a shame cos I'd hoped that this might be something that, you know, owners could be doing to try and reduce those, tumours on a, on a more daily basis, but I haven't yet seen anything come out, from them. So immunotherapy is a great idea. So 2016, this group did some work on it.

Morphogenesis is a group in America who are making it annoyingly. We can't still get it in the UK. I emailed them again and they said no, so it's not even an option for us over here.

There are all sorts of autologous vaccines. There is now a company in the UK who are making autologous vaccines with some pretty, Broad claims on their website with no actual research that I can find . So I would be very, very cautious with these autologous vaccines, and.

There might be legs here. I'm never, never gonna say it might not, it won't work, but care with them. And I'm not sure what the new company's vaccination, how it works, what it's made of, etc.

Because that information isn't readily available. So this the details on this page are based on the morphogenesis company, which is made in America. .

Their study had end of one really helpful, and they did lots of injections, so. Yeah, I'm just not pushing it, sorry, that's that's probably the summary of it. Except on the other hand, I, I, I'm a fairly big proponent of, I think it's a really good way of controlling these cases.

Licenced for dogs with melanoma is not licenced in horses. When I first talked to bos, I point out that I'm not expecting a solution of my lens. I'm not expecting them to disappear.

What I'm expecting or hoping for is stagnation of the tumours at the at the stage they're currently at. I monitor these very closely, so monitor, map and measure all melanomas on day one, and then every time I go back apart from that first loading protocol time. What I'm finding is the vast majority of my cases are stagnating very, very well, so I'm really pleased with where they're at.

The problem is the cost associated with it, so lots of owners aren't willing to do it. But I do point out that even if you've got insurance for 1 year and we do 1 year, that might be 1 year of pause in growth. So it's always worth trying to do a year or 2 years, whatever it is, and if we stop, it doesn't matter.

You've at least gained a couple of years. It's 2 injections, sorry, 4 injections every 2 weeks and then every 6 months thereafter. Theoretically, it's only to by a medicine or an RTVF specialist, although there seems to be some nuances in that, thanks to, some groups who are very willing to put their name to other people injecting these things.

So, yeah, I, I would recommend that we stick with the, the rules and the regulations, but that's me. There is more research coming out now, so actually there's some, some good stuff that has shown a good response in these cases. In 2012, a group confirmed that the Tyrena in there, so these should theoretically work.

Then looked further and found that there was a response to the vaccination and no side effects other than some local swelling. I have had one case recently that needed but every time I injected it, and that was it, just be on day, but the day after. And Fernando Milana company a year ago, didn't have much success with some melanomas in the eye, with it, but slightly different case, you know, you're, you're choosing it probably towards the end of the treatment course or the, the hopeful, the progression of the disease.

Some more other conversations I've had though is that there is some research coming that has shown really good responses. So I, I think it is very much something that we should be using in these cases. Others have tried to link it in with a few other interleukins to try and increase the response to the, the vaccination, so looking at IL 12 and 18 and then adding like protein 100 and thyroidase.

What they found is that it. All of these led to a tumour reduction in size, and that actually the glycoproin and thyrozinase had no additional effect, so could we be using IL 12, IL 18? Frustratingly, at the moment there is no available options for either of these, but maybe that's something that will come in the future.

I just put this in because I think it's a squamous cell carcinoma rather than a melanoma, but it's amazing what people do, amputating a limb on a Shetland pony and supposedly it's doing all right, at least as of the study, the end of the study, but, you know, it just shows what some people will do and can do in these cases. That slightly into the wrong place there. So for melanomas, benign neglect is not a treatment option of choice.

Obviously sometimes it has to happen, but we should be being proactive as much as we possibly can to remove those when we've got the option. Can be fatal due to local growth, er and therefore let's get this surgical excision. Consider onset for me, and I wouldn't be really doing chemotherapeutics, just repeat surgeries as much as, as is required.

Pre brief little section, lymphoma is a much bigger, it's just multiple talks by itself, but I'd be silly not to mention it, and I haven't mentioned lots of the other tumours that are out there because it's just too many, and I think it's more important to look at things that you're gonna see every day and be able to give you the information and the armoury to talk to owners and provide all the options required. Lymphomas, 3% of equine neoplasia can be one of four groups of multicentric alimentary mediasty cutaneous. I think we see a lot of alimentary, a lot of cutaneous, very rarely multicentric and very rarely mediastinal.

Clinical signs depending on where they are, so really complete lethargy, skin disease, whatever it might be, possibly a thoroughbred predilection, and it seems to occur in 5 to 10 year olds, also there seems to be another bracket as they get older, but definitely it seems to be in that younger category that you see most, most of them. Paraxia seems to be often with them, and whether that's paraneoplastic syndrome or if that is something else we don't know. Diagnosis is, sorry, biopsy is essential, and that can often just be a true cut needle, and that'll give you enough peroneal fluid, very rarely helpful even in the alimentary form, so don't, don't bother with it too much or don't, if you get a negative, sorry, don't assume it is a negative.

Ultrasound is always essential, and particularly pay attention to that wall thickness because that can be your first indication that there is a lymphomatous disease process going on. Dacytiology is, is not known. In humans, it can often be associated with a viral challenge in horses there seems to be an inflammatory process, quite a lot more than there is a truly neoplastic.

So they really do respond to steroids very, very well, at least for some amount of time. And so. If it's a single single focal nodule, then getting rid of it is the right thing, but if it's lots or it's in intraabdominal, then steroids can be very, very effective.

It's quite useful to do some immunotyping, just to make sure you know what your prognosis, be bad, terrible, so B cell rich or T cell rich. And it can be a grave prognosis. I would put a caveat with that, that the cutaneous ones seem to do relatively well for quite a long time.

At some point it will catch up with them, but you can normally buy enough time that it's well worth treating, well worth monitoring these horses. Chemotherapy is also an option. We would have done cisplatin, but also we've done various doxorubin, LS barge, cyclophosphamabia thiscristine protocols, .

The problem with it is that you don't, we don't have the data to be able to provide that to an owner to say, OK, if we do this protocol or top protocol or whatever it might be, then we're going to have success. So it's very hard to sell this, especially at the cost within the UK, you know, in America it was actually financially viable, over here it's just financially crippling. Corticosteroids are probably the mainstay after surgical excision, and so yeah, Preds normally OK.

Dex if you can get Dexin IVIM, is going to be far more cytotoxic to the leukemic lymphoblasts, so well worth doing dexamethasone if we can. Radiation again, just there for information rather than expecting anyone to do it. So thorough, well done documented work it gives you a good starting point, can give you the opportunity to monitor as you go forward.

Assumptive diagnoses aren't appropriate, not, not anymore. We can do better than that. So get a biopsy as long as treatment is an option.

The historic fear of biopsy should be lost now as long as we can crack on. Wait and see approach is not OK. If it is going to be done strict guidelines, so tell the owner the tumour is this size today, if it goes up to this size, monitor it, then we need to get it removed whilst we've still got the option before it gets too bad, because it's amazing how many owners come back 5 years down the line and say, now fix it, please.

And there are so many therapeutic options out there, it really is a bit of a minefield, but hopefully this has given you some of the, the tools to be able to decide which ones are the appropriate ones and how you can progress to give that horse the best option. So thank you for listening, and there are a couple of pages of references, just so you've got them, you need them. Thank you very much.