Thanks very much. Guys, I got a confession to make. This is my first one of these, webinar, so, bear with me if I get it wrong.
And the other thing I was also gonna say is I've sort of stepped in for David Argyle, who, can't be with us today. So if occasionally I stutter a little bit more than I normally would do, then, just bear with me. So what I'm going to do today is talk about, cats, and my plan for the first lecture of cats and not small dogs, is to talk a little bit about, similarities in treating cancer regardless of species, and essentially, that is to make you a sort of instant oncologist, and, then we'll talk.
About where cats are quite different for dogs, sometimes in ways that you would expect, and sometimes not. And that will cover things like, prevalence of disease and, diagnosing the disease in the first place, and disease behaviour from, from one to the other, as well as treatment, options. So that's just to give you a kind of, broad plan of, of what we're gonna do.
So, let's start off with, how people feel about cancer. So the first thing to appreciate is we talk about cancer as if it's one disease. It really isn't.
It's up to 200 different diseases, certainly in, in, depending on the, the, the, the cell of origin of the cancer, and therefore, we've got 2, 200 different diseases to think about. But, basically, if you're. Client walks through the door and you say, I'm terribly sorry, Mrs.
Bloggs Fluffy has an infection. The response that you'll get if you say, I'm terribly sorry, Mrs. Bloggs Fluffy has cancer, is going to be completely different.
And, you know, the clients usually have, an experience of cancer associated with, their friends or their relatives, and frequently, until pretty recently. The word cancer meant a death sentence in people's heads, usually preceded by unpleasant treatment modalities, people with their heads down there to the toilet, vomiting and, and, you know, how, how the media presents cancer. So not only are we dealing with the actual disease itself, we're very often dealing with the emotions that arise when you start to Discussing this disease.
But cancer, just like infection, has quite a wide prognosis. You know, if you have a common cold, it's an inconvenience, at worst, and you get over it. If you've got Ebola virus, then obviously your prognosis is a lot more guarded.
And something that I think people don't appreciate is cancer is the most curable chronic disease, that we see. So if we look at these two pictures here, we've got a cat who's got a couple of lesions on, on its chin. These are actually basal cell carcinomas, and basically, if you take these off with not much cats attached to them, that's going to, sort them out.
This cat here has come in with quite an advanced injection site sarcoma, over the intrascapular area. And what we're going to be able to do for this cat is going to be quite limited by the advanced nature of the disease. So let's start off by what is the same regardless of whether we're treating a cat or a dog or to a certain extent a person as well.
And what we're really looking for is the answer to two, important questions. The first question is, what is it? Is it actually neoplastic or is it something else?
And if it is a tumour, what type of tumour is it? Because that's going to tell us whether or not it's going to be a disease that we can sort out by concentrating on the primary that we can see, or whether we have to worry about systemic spread. And then Just because this disease has a low risk of spread, is that actually the case in the, in the animal that we're looking at in front of us?
So what we're going to look at is where is the disease in this individual animal? And this is going to be, related to what we talked about before, which is the stage of the disease. People frequently get stage and grade confused.
The grade of a tumour is actually the likely aggressiveness of the tumour. So you're looking at a a a a a biopsy and you're going, actually, there's lots of cells that are undergoing mitosis. The cells look very different from the type of cell that they arose from in the first place.
And this tends to say this is going to be an aggressive one within that tumour type, or maybe the cells look very similar to the normal cells that you would appreciate from, from, the normal tissue in that area. Maybe they have a low mitotic index and essentially these are, are likely to be a more, benign end of the spectrum of that particular tumour type. So stages where the tumour is, how much tumour burden is the animal, carrying and grade is how aggressive is this tumour type like to be.
Cancer is a disease of older animals, so we're often, obviously looking for concurrent disease. Do we have to worry about, you know, incipient renal insufficiency in this animal? Has it got hyperthyroidism as well?
Does it have cardiac disease? We also have to take in mind when we're treating animals, what are the owner's wishes, and that is obviously coloured by Sometimes Dr. Google, or it's coloured by their own experience of cancer treatment.
So you have to manage, those expectations. But also client resources. And when it comes to client resources, we have to think about not only money, but also, a time resource.
Are they willing to travel to somewhere that has radiotherapy, for example? The other thing I also think's important is that we look at what we're planning on doing to this animal, what are the risks to quality of life, existing quality of life, and what are the benefits that we're actually gonna offer this animal? Are we going to do a, a massive surgery that actually might only buy a short period of time, and that whole period of time is spent with the Animal recovering in hospital, is that really very fair for everybody?
Or are we going to do something quite simple that essentially going to bring us a long period of time and give us a good quality of life? And that comes back a little bit to what Doug discussed when he talked about the use of chemotherapy and lymphoma, where the client's satisfaction rates are extremely high and they would do it again. And for example, with those cats, the quality of life actually improved while they're receiving chemotherapy.
And also, what I'm going to do a little bit will be coloured by whether I think I'm doing something that's palliative or whether I'm doing something that's curative. I may be more aggressive, maybe with something that's a curative, intent, that may cause, for example, Some soreness during radiotherapy, skin soreness, but we know that's gonna go away and we're going to give a good long period of good quality of life to an animal than if I'm going to make them very uncomfortable for no long term benefit for the animals. So I'm gonna think about that.
And also, I'm going to make very clear that the owner understands exactly what we're trying to achieve. Some clients find it quite difficult to understand that what we're actually doing is time buying in a lot of situations, not necessarily curing them. So, as an, my, as an oncologist and as a general practitioner that's practising with oncology, I think those two questions, what is it?
Where is it? And, an assessment of, the animal that is in front of you and what you're planning on doing's success rate and how, risky are the, the side effects or, or the, the, the, the potential, bad, effects of what you're doing are quite important. So how do we find out what we're treating?
Well, basically, you can use fine needle aspirate, and that frequently is a cheap, easy way of, of getting a diagnosis. But as Doug said, it's not always representative, particularly if you're looking at a low grade lymphoma, where essentially the cells will look very similar to, the normal cells in that area. It's very useful if you've got cells that are gonna be highly atypical.
If you've got a skin lump, for example, the other thing you have to be aware of is what exactly are you sampling. So if we look at this kind of elegant representation of a lesion, not that I produced, we can see that our neoplastic tissue has got a central area of necrosis and it's got an area of inflammation around, . The actual tumour itself.
So where you stick your needle may well give you either a useful answer if you stick it in the tumour cells. If you stick it in the inflammatory cells, then obviously you're not going to get anything useful. But what you may well have as your differential for a lump is it's of inflammatory origin, so that really isn't gonna help at all.
And If you get necrotic necrotic mush on your slide, then essentially that's not really going to give you an answer as well. So, essentially, just for interest, this is a canine Marcel tumour sample, and this would be something where an FNA is very useful. Marcels are, are, are tumours that shed very easily their cells into a needle, and also they're very distinctive with those granules that we can see in, the cells, quite obviously like spotty fried eggs.
So the other ways we can sample to get a, a, a, a diagnosis is to go for an incisional biopsy or an incisional biopsy. And there are pros and cons to, both of those options that we have. So essentially, an incisional biopsy is where we take a sample from our area of investigation, not the entire abnormality itself, and we try and take a piece of normal tissue, alongside the area that we want to investigate because very often, the pathologist will be interested in the interface between the abnormal tissue and the normal tissue.
To be able to tell us, for example, whether or not this is a malignancy rather than a benign mass because, malign masses grow in an expansive fashion, whereas malignancies you have interdigitation between the normal tissue and the, the, the neoplastic tissue. So taking that interface is quite an important thing to help our bio our pathologists. When I was in general practise, what used to happen in real life was that dogs or cats were booked in for a lumpectomy.
So we wouldn't know really what we were treating, and what we would do essentially is an excisional biopsy. So you just take the mass, that was presented in front of you and send the whole thing. To the pathologist.
And what you'd be hoping is that you would essentially be doing this. You'd be taking off the neoplastic lesion with a margin of normal tissue around it. And so essentially, your biopsy technique would also be your curative surgery at the same time.
But the problem sometimes is that when you do it, actually, what you don't appreciate is that the normal, so-called normal tissue around the the mass is actually infiltrated neoplastic cells. So there's a risk that you'll end up doing something like this and actually leaving neoplastic cells behind. Now, the problem with that is that essentially, you're gonna have to do a second surgery to mop up those cells that you left behind.
You haven't got a mass anymore because you've taken away the mass. So you're having to have a best guess as to where you're actually going to do your surgery. And you've probably interrupted the fascial planes, you might have done a bit of blood dissection around the mass itself, and you may therefore have kind of seeded the tumour into areas where it previously wasn't.
So basically, if you're going to go for this sort of technique, then you need to be quite clear in your mind that you can actually go back and actually do a, a, a, a decent surgery afterwards and, not have actually compromised any second surgical technique. So a classic one for a sort of excisional biopsy might be a, a small nodule within a mammary tumour. For example, where you can do a follow up mastectomy relatively straightforwardly or or even a wider excision if you need to.
Just out of interest for cats, most cats do not get benign mammary lesions and therefore, that argument really only applies to taking a nodule out of a mammary tissue to, to a, to a dog. Just a quick reminder, that, essentially you've taken your biopsy, you've got something coming back from the pathologist, and it's gonna come back into sort of realistically one of three groups. It's either gonna be a carcinoma or a sarcoma or a round cell tumour.
So essentially, if we're looking at the carcinomas, where does that name come from? Well, if you cast your mind back to embryology, which I have to say I successfully snoozed through on summer afternoons, I think in first year, of my undergraduate. Course.
Essentially, when you're in the womb at a certain point, you look like a sort of bead. And what you are essentially is a whole pile of cells around the outside, a tube down the middle, and for want of a better term, squishy stuff, between the outside and the tube. And the squishy stuff is gonna form muscle and bone and cartilage and tendon and all those sorts of things.
And that squishy stuff is referred to as me and chime, and that's where our sarcoma tend to arise from, in, in later life, osteosarcomas, chondrosarcomas, and the soft tissue sarcomas. And then around the edge, that's gonna form, skin, eyes, and those sorts of organs, and that's going to be carcinomas, in later life. And the tube down the middle is gonna form your digestive tract and your lungs and things like that.
And again, that's where they become carcinomas. The round cell tumours. Tend to be hemopoetic in origin.
So basically that's how it all, how it all works out. Why is this remotely interesting? Well, because if you're going to do a finallape and you're going to get a cytological preparation out, then, basically these three groups are things that you can successfully.
Divide the cells, types into from your cytology. So carcinomas, tend to be cells that stick together, on the slide, and, you can sometimes find them in little rosettes, and that is a sort of classic carcinoma, presentation on a finely lapirate. And if it's a sarcoma, then you're gonna see these more spindoloid cells.
Generally, sarcomas don't shed as well into the needle hub when you're doing a fine need aspirate in comparison to . Carcinomas or round cell tumours and round cells basically float around. They don't really want to sort of hang on to each other and by definition they're around and like we said, these are the hemopoquatic cells and and transmittal neurogen which is something we don't have to worry about in the UK.
Doug also touched on immunohistochemistry because sometimes when you get your tissue biopsy sample back, the cells are so different from the cell of origin that the pathologist can't really tell you very much apart from they are probably neoplastic. . And equally, the other problem we sometimes have is with GI lymphoma in cats where essentially IBD cells look like a, a, a population of, of small lymphocytes and low grade GI lymphoma also looks like a population of small lymphocytes.
So one of the things we can do as, as Doug alluded to, is to stain these cells up with particular anti antibodies to particular antigens on the cells to identify the cell of origin. So this is a lymph node and this lymph node has been stained with CD3, which is a T cell antibody. And what we can see is that we have T cells in certain areas and we have blue unstained cells in other areas.
This is where the B cells are living and these are where the T cells are living. If we look at this slide down here, we've stayed with CD79A, which is a B cell marker, and what we can see is basically the B cells are living in these nodules here and the the unstained cells of the T cells. So that's a hyperplastic lymph node.
If we look at these samples here, what we can see is when we stained with the T cell marker, it's a sea of brown and basically the T cells have taken over that lymph node and squashed the B cells into kind of small areas. So the whole lymph node. They faced the architecture is faced by the neoplastic process.
And if we look down here in this corner, then this is a B cell lymphoma, where essentially we've got the whole lymph node effaced by the B cells. The architecture again has been destroyed. So we're not really that bothered about TMB being predictive for cats.
Broadly speaking, but this is a, a, a good example of the technique that we would use for GI lymphoma when we're trying to look for a clonal expansion that isn't always very convenient, in GI foam with cats, but it certainly is, is something that we can we can look for. But the other thing I'm trying to illustrate as well is that we've used, the, lymphoma marker CD3 and CD79A. But we can use other histochemical markers that would example, if we're talking about a dog, we might use CD 31, for example, to identify hemangiosarcoma cells.
So we can use it to tell us where the expansion has been, and so that's a useful thing, but we can also use immuno histochemistry to identify the cell of origin if it's not clear. So, we've identified our tumour type, like I say, for some tumours, there's quite a wide range of behaviours and so we may want to know something else about, you know, how well is this tumour gonna behave within. The, the, the tumour type that we've identified.
So this is an old paper by Castagnaro Eal, which is looking at mammary tumours in cats and dividing them into three grades. They were all treated with surgery alone, and they followed these cases out for a year. So basically, they had, 7 cats who had well differentiated mammary tumours taken off, treated with surgery alone.
And, 33 that had, an intermediate graded tumour and then 15 of them had a poorly differentiated tumour. And we can see at the end of the year, the cats that had the well differentiated tumours removed were all alive and unfortunately all the cats with poorly differentiated tumours had died. And so you can see that obviously in this case, this grading system is extremely prognostic for, for outcome.
So we now know what it is and we know now how aggressive it's likely to be, then we ought to go and have a look really and see exactly where this disease is. So this is what Doug referred to as a workup, and essentially what we're doing is staging. So we're looking at the extent of disease and we can do that through several things.
We can start off with a thorough clinical examination that's gonna give you a, a pretty good hint if, if you've got an animal that's dysneic, for example, with a mammary tumour, then that's suggests that maybe you've got a, a problem on your hands. Equally, if you've got a, a big lymph node related to a particular, you know, the area where the tumour is a draining lymph node, that again is going to suggest that things aren't as they should be. We can, use things besides a clinical examination, we can think about fine needle aspiration of lymph nodes, to look for, neoplastic cells, metastatic cells.
We can use radiographs, we can think about ultrasound, and we can use, more advanced imaging like MRI and CT. So we've got some pictures here. This is a cat with an injection site sarcoma is an MRI.
And in over here, what's someone doing ultrasound. I just want to draw your attention to this radiograph here. This is obviously a, a, a, a lateral thoracic radiograph of a cat, and please note this slightly diffuse lesion up here in the corner.
So one of the things that you really need to, to know is the disease process because that will tell you where to go and look for the disease, . For example, we just said mammary tumours, classically will metastasize to, the chest. They will go to other places as well.
But essentially that gives you a chance to know you should take a chest X-ray for that disease. Marc cell tumours on the whole don't, end up causing, thoracic lesions. So probably you would be better off spending client's money looking elsewhere in a different way.
This animal, this picture here that we can see, is related to that thoracic radiograph I just showed you. This is a condition called lung digit syndrome, and what's really cool, not for the cat, but, as an intellectual, premise, is that the primary is actually that chest lesion that we saw the thoracic lesion we saw, and these lesions that we can see, facing P3 are essentially the metastasis. And we know that because if you biopsy these, what you end up seeing is respiratory viy within the paraffin fixed tissues that you have.
So that's pretty cool. So we said, you're gonna look for lymphadenopathy, you're gonna do a good abdominal palpation. If you're a cat, it's a bit difficult to do a rectal examination, but certainly, that's something we, we're not very good at doing with dogs, particularly in disease at the sort of back end of the dog.
Something else we're not very good. That when we're looking at neoplastic disease is ophthalmological examinations as well. And the other thing you got to remember is you're not just looking for evidence that the tumour has spread, but also you're looking at concurrent disease that might impact on your owner's decision whether to treat this neoplastic condition or whether to modify how we're going to treat this in the in the light of the neoplastic of the concurrent disease.
I just want to put up a sort of evidence of how of how we stage. So, the classic way of staging is the TNM staging system where T stands for tumour, N stands for node and M stands for distant metastasis. And this is the classification for epidermal origin.
So basically, T0 is a, is a, is a radiation addition where we got no evidence of tumour at the time of presentation. TIS means that we've got carcinoma in situ. In this case, that means it hasn't breached the basement membrane of the skin.
T1 is a superficial smallish tumour, T2, the tumour is getting bigger or it's invaded. T3 is, it's even bigger or even more invaded, and T4 means that it's essentially invading other tissues. And this basically is useful for prognostication for the client.
It's also useful from the point of view. Of giving us a baseline from when we start treatment. And it's also going to sometimes influence treatment.
If we're thinking of nasopplaum tumours, for example, then what we can offer for the more superficial tumours is going to be quite different from what we can offer for some of the bigger tumours, with, with any degree of success anyway. So, interestingly, John mentioned, looking at quality of life, and that is something that is very important to us oncologists. Our philosophy is essentially to improve quality of life, to increase length of life, and just because we can do something doesn't always mean that we should.
This cat here that we talked about earlier with these multiple lesions, was treated very successfully, with relatively conservative surgery. She was 14 at the time, and some people might have said, well, she's 14, what's the point? Well, you can see this is ulcerated, she was licking it, it was bothering her.
We did a straightforward smallish surgery and that's it fixed. So why wouldn't you? So the reason probably I became an oncologist is because our treatment options are relatively straightforward.
We have a choice of 3. So, increasingly maybe 4. But we start off, we've got surgery, we've got radiotherapy, we've got chemotherapy, and then our immunotherapy is starting to make an appearance for some tumours, other medical therapies, tying kinase inhibitors and so forth, are, can be considered.
In there as well. And essentially what you do to treat cancer is you may decide to just use one modality of treatment or frequently we use multimodal treatment. So for example, you might use surgery to debulk disease to get down to microscopic disease and then following radiotherapy.
You might use surgery to get rid of a primary and then follow on with chemotherapy to deal with the micrometastatic disease, that sort of thing. Just out of interest, this is a cat with a very large thymoma. His name was Tyson.
And you probably appreciate that Tyson was quite skinny at at the time that we treated him. And we didn't really understand why he was called Tyson because, when we first met him, he was, a very, amiable cat. We treated this thymoma with radiotherapy, the thymoma shrank, Tyson had a slightly more space to breathe, and that became very obvious why Tyson was called Tyson, because then he became a very difficult cat to handle indeed, and spent more time suspended off, various members of staff with his teeth stuck in them, than we would have liked.
But, we treated him very successfully with radiation, and he did, nearly 2 years, after we irradiated that mass. You can treat thymoma very successfully if they are surgical with surgery as well. Decision making is gonna be, firstly, is it cancer?
To find out if it's cancer or not, we're gonna need some sort of, sample, cell sample of some variety. It's nonneoplastic, my first question is, is that a believable, results, or have we just sampled the inflammation around a mass, for example? If it is believable, we're gonna treat it appropriately.
If we really don't believe it, we're either gonna get a second opinion on the sample that we've taken or we're gonna take another sample. If it comes back that it is actually near plastic, then we're going to do a good clinical exam, and we're going to assess the primary tumour, we're gonna evaluate for concurrent disease and we're going to decide whether or not this tumour needs staging based on the tumour behaviour that we know if it's a tumour the very, very low risk of metastasis. This we're gonna do something relatively straightforward like that cap we talked about with the lesions by the lips, then essentially you may well want to go to straightforward therapy.
If you feel that actually you're going to do something it's invasive or there's a significant risk of metastasis, then you'll like to go down this pathway. So essentially that's gonna be the way you're gonna work it up. If you do feel there's a significant risk of metastasis, then you need to think about systemic therapy as part of the treatment plan because otherwise, essentially what you're doing is palliative.
So like we said, if it's local disease, you're gonna use surgery or surgery and radiation or radiation alone. If you've got disseminated disease, you're going to be thinking of using cytotoxics in reality or some other sort of medical therapy either before or after treatment of the local disease or as part of the treatment of the local disease. So surgery, if you are This cat here with a basal cell carcinoma, he's been renamed recently, then essentially you're going to, take this off with not much cat attached to it, and that's gonna be, with curative intent and very likely the cat's gonna live happy ever after.
Sometimes you might want to use surgery for an ulcerated mass in an ulcerated metastasis, for example, where a straightforward minor surgery with two or three sutures is going to get rid of that ulcerated area and give some relief to, the animal. . And you may be using surgery with adjunctive therapy, which is basically like we said before, a debulk where you get rid of most of the cells and followed up by radiotherapy.
And it's important or although painful for me to say that surgery alone cures more tumours than any other modality. So a vast majority of animals, don't need to see me as an oncologist. But what is important is that you actually know what you're treating.
We said there's a real risk with an excisional biopsy that you may leave microscopic disease behind and that makes life very difficult either for yourself or the surgeon who comes afterwards. So a shining example of that is an injection site sarcoma. So, if you take off that injection site sarcoma, with very small margins around it, we know that these recur extremely quickly within about 60 days.
And equally, if, you do that and then send it off and ask someone to do a second surgery, of, in that situation, again, recurrence is extremely likely. The most successful way of treating an injection site sarcoma. That sounds pretty hideous, but realistically, you're looking at a 5 centimetre margin around the mass and two fascial planes deep to give the best chance of success.
So basically, an an incisional biopsy, get a diagnosis and follow it up with, referral is probably the best way to treat an injection site sarcoma. So, these can be very challenging, and do need quite a lot of post-surgical care. When you are biopsying the when you are treating the tumour, don't seed it.
So basically, don't do that blunt dissection unless you're very clear, you've got clean margins. Approach it as what's called a cookie cutter approach, which is essentially going down with, a straight line, 90 degrees to, the skin, and don't compromise on that. This is why I'm not a surgeon because I know I would be a coward in this sort of situation.
The easiest way of making yourself, stick to those rules is to draw out your margin, make the hole, and then worry about how you're gonna fill it up afterwards. I'm told by the surgeons. I'm sure I wouldn't be that brave.
The other thing is, it's very useful for once you've taken that lesion out of your, to ink your margins. So essentially, Do this with something like a waterproof ink, you can use Stevens or something like that. Let it dry before you put it into the formalin.
And if you've got a particular margin that you're concerned about, then do draw the attention to that margin with the pathologist, either by putting A little suture in it or even taking, I know one of my surgical colleagues who takes a, a, a further small biopsy and puts that in a separate pot and says have particularly look at this. So for example, if she was concerned about a margin here, she would take a small piece of tissue, put it in a pot and say, can you see whether that area is dirty? The other one I've seen quite frequently is multiple lesions stuffed, heroically by a nurse into one set of formula, because that saves money on the postage.
Well, that's lovely if they're all benign lesions, but if you've got 5 lumps in a pot and one of them is malignant and you the margin on it, then life becomes quite difficult to identify. So we've talked about surgery being very a good option. The other one that is a very good option to treat local disease is radiotherapy.
This is Liverpool's old machine. And this is what's called a linear accelerator and or sometimes we refer to external beam radiotherapy, where the animal is positioned on the couch down here and the beam comes out from up here from the, the, and it basically that's how, how, how it does what it needs to do. Down here, this is plesio therapy.
What we've got is a applicator and at the end of here is a piece of of metal impregnated with strontium 90. And this is predominantly a beta radiation source, which is why we've got the perspex to protect the person who's administrating the administering the radiation. And this is a very type of superficial radiation which can be used for noses.
And then there's also brachytherapy where you actually use something like a radioactive wire or a radioactive bead. To, either, you, you implant them in the tumour and leave them within the tumour, or, you can put them through, a cannula and allow doses to be delivered as you go along, within, a tumour, bed. So essentially, when we talk about radiotherapy, we tend to mean external beam.
It's a sort of, we're a bit lazy about that. So we can use it as adjuvant therapy after surgery for mostly microscopic disease and this is potentially can we think of as a curative for things like soft tissue sarcomas in in dogs and mat cell tumours in dogs particularly. We can use it for gross disease for certain tumours, and that usually is palliative unless we're looking at a lymphoid tumour and we can also use it for pain relief for things like appendicular osteosarcoma in the dog.
So this case here is a case of nasal lymphoma in a cat. You can see on the lesion here and you can see there's fluid accumulating in the sinus here. This is an MRI and This is the cat afterwards.
This cat was very lucky because the turbinates weren't particularly involved. And so basically, when we finished the radiation, the the tumour had completely gone and the cat's anatomy returned back to normal. Sometimes what you find is because the lymphoma can be a bit destructive, then you end up losing the turbinates, you end up sort of the gap there rather than, this nice picture we can see here.
So if we have systemic disease, then essentially we're going to have to think of some sort of systemic treatment. So we're going to be using cytotoxic drugs and maybe receptortizine kinase inhibitors. We can use it for palliation or cure alone.
So obviously with the lymphoma, we would be using it, on its own. There's no exceptions the lymphomas and radiation or, we'll talk about nasal tumours in a bit more depth in our next lecture. We may use it as neoadjuvant therapy, to try to reduce the lesion, to shrink down a lesion prior to surgery, or we may use it as adjuvant therapy post-surgery.
So for example, primary tumour in the cat where we have a high risk of metastatic disease, there is a little bit of a debate as to whether or not we should be offering, post, surgery, treatments to these. That's something we can always discuss with Doug. Personally, I do tend to offer doxorubicin as, as, for there is a high risk of metastatic disease.
So, people have used in injection sites sarcomas, drugs prior to a surgical procedure. There's a study looking at using epiruicin, giving a couple of doses before surgery, then performing a surgery, and then following up with epiruicin. It was extremely successful, that particular study.
The, one of the things just be aware of is that those tumours were quite small. They were, not having breached, out of compartment they were arising from, so that made the surgery a little bit more straightforward. And the other thing we have to think about, for, both cats and dogs is, is obviously supportive care.
We need to be, thinking, be very mindful of pain relief. We've obviously got meloxicam, which is licenced for cats in the UK. Rubella Coxi has appeared fairly recently and, I've got a lot of experience of using it in cats, from the point of view of cancer.
We've also got the opiates as well. . Sometimes, getting rid of some of the inflammation around a space occupying lesion in itself can improve quality of life.
And obviously, there's a role for non-steroidals and, and, prednisone in that. And then other things you might be wanting to think about are obviously antiemetics, antibiotics and dietary sport. If you've got an oral tumour, and that's something we got to be thinking about as well to, improve these animals, quality of life.
So what are the special considerations that we have with cats? Well, the first one Doug's mentioned a little bit about is, diagnosis, where things might be slightly different. So cats have a lot of this low grade GI lymphoma, and this is gonna be challenging for, your clinical pathologist to diagnose on FNA.
And so it's going to be quite common in those sort of situations to want a full thickness biopsy to get an an accurate diagnosis. Most cell tumours in dogs, the vast majority of them are going to be relatively straightforward diagnosis by FNA. Some of the more anaplastic ones might not be.
In cats, the histiocytic variety, can be quite challenging to diagnose. And again, the more anaplastic variety in cats can be more difficult to maybe, taking a biopsy more frequently than you would do in, in a dog bearing a mat cell tumour. Basal cell tumours have been recently subdivided into other types.
They were all lumped together as basal cells, but some of them are turning out to be. Other types of, of tumour, but a classic, basal cell tumour is, pigmented on FNA, and people can think that they're dealing with melanoma. Melanoma in cats is, is relatively uncommon.
And injection site sarcomas, you're going to really need, an incisional biopsy. Occasionally you can diagnose them on FNA, but just be aware of that. So tumour behaviour, certain tumours, you know, they'll be coming from the same histotype and therefore there'll be an assumption that they're gonna behave in the same way from species to species, but some of them don't.
So appendicular osteosarcoma in the cat, unlike the dog, has a low risk of metastatic disease. Cutaneous squamous cell carcinoma in the cat is, a relatively common presentation certainly, in in areas where it is sunny and is associated with UV light. It's not really clear that there's an association with dogs.
And if we do have a cat with lymphoma, we don't usually see hypercalcemia. We tend to see hypercalcemia quite commonly in dogs that are particularly associated with mediastinal lymphoma. If we look at the prevalence of different tumour types, then, if we're looking at oral tumours in dogs, we tend to see squamous cell carcinoma, leant melanoma and fibrosarcoma.
In cats, it's vast majority of the tumours we see unfortunately are squamous cell carcinoma, and about 30% of the fibrosars. I'm just neatly ignoring the, the more rarest subtypes that we sometimes see. But melanoma is quite rare.
Lymphoma, type that we see depends on FERV status and also we tend to see much more extranodal types of lymphoma in cats than we do in dogs, for example. If we think about cutaneous tumours in cats, at least 70% of them are thought to be malignant. So if you're seeing, whereas in dogs, it's the other way around.
And in dogs, hepatic tumours, primary tumours are more likely to be malignant than benign. In cats, it's the other way around. We have other considerations, to think about that we don't really think about with dogs particularly, although, there's, some interesting work coming out on that.
But, basically, we're used to thinking about, feline leukaemia virus and feline immunodeficient virus in cats. And in the days when FELV was quite prevalent in the United Kingdom, then essentially we were seeing it in young cats. It tended to be T cell derivation, it tends to be multicentric.
Now we've got our FELV vaccine around and we're seeing considerably less FELV positive cats. We're tending to see older cats with low grade G GI lymphoma. And as Doug said, if you are FELV positive cats, you have an increased risk of developing lymphoma, and also you will respond properly to the cytotoxic drugs that we use, but you won't respond for as long as you would do as if you were a FELV negative cat being treated with lymphoma.
And with FIV, we know there is an increased risk of developing lymphoma. There's some studies out of Australia where FELV is traditionally not very common that show that there's a link between FIV and the risk of developing lymphoma. The other viruses that we have to think about in cats are the papilloma viruses.
We do know there is a type of squamous cell carcinoma which we'll discuss in the head and neck cancer lecture. Which we tend to refer to as Boeing's disease, which is very clearly related to the feline papilloma viruses. But there is a question mark about whether or not there is a role in the other forms of squamous cell carcinoma and there's some, authorities studying that.
So we're gonna talk a little bit about the cytotoxic drugs. And, the first thing to appreciate is that the body surface area chart between cats and dogs is slightly different. So just, look at the, we tend to look at the dogs with two decimal places after the, when we're looking at doing a calculation, after the main digit on the, on the right hand side, in cats there's a, there's usually a third to digits to look at.
And the dose is probably, not the best way to calculate it below about 15 kg body weight anyway. So, what you find, for example, with carboplatin is that we will be using 300 milligrammes per metre squared for dogs. We tend to use about 180 for cats.
Be aware also that carboplatin, is cleared predominantly by the kidneys, so that's obviously an issue with an older cat. Doxorubicin, as Doug said, is nephrotoxic in the cat and that's probably it's dose limiting toxicity, cumulatively, and we should be checking your creatinine every time we're using it. The dose rate is slightly complicated in cats.
I've written down the lower dose of 1 milligramme per kilo. But some people will be using 25 milligrammes per metre squared. So it's quite a wide range of dose in the literature, to be aware of.
Cisplatin, not that anybody uses cisplatin commonly these days in the UK, but that will kill cats quite successfully, and 5FU isn't something you should be using in cats either. Doug mentioned, that lowmine ham, if you keep using, sequential doses of it can cause pulmonary fibrosis in cats. Cats seem to tolerate walking around with not very many neutrophils, relatively straightforwardly, but they do tend to go off their food, probably more frequently than dogs.
And I think there are, a couple of reasons for that. One is that, Elis, as we discussed, associated with Christine is something that we see relatively commonly. And in my experience, that's been with the higher doses.
So if we're using 0.75 milligrammes per metre squared in some of the lymphoma protocols, that seems to sort of trigger it more commonly than if we're using 0.7 or in some protocols, it's even as low as 0.5 milligrammes per metre squared, and we seem to see less problems with a slightly lower dose.
. Cloambiil is well tolerated, and we use it for GI lymphomas we talked about, and cyclophosphamide is well tolerated in cats. We tend to use it orally in the United Kingdom, which again, sometimes means that we have to recompound or accept that we're gonna give a 50 milligramme tablet and then, not give it that, that, that, that next dose, very frequently. Hemomatic cystitis is not, reported in the cat like the dog.
And like we say, with low mustine, generally, it seems to be, well, better tolerating in cats and dogs. We don't see hepatotoxicity that we see in, dogs, but pulmonary fibrosis is reported. So, what about side effects that we have to worry about?
Well, we should be taking a baseline blood out of any animal that we're going to treat with chemotherapy, to understand, how the animal's performing, generally, how, well those organs that are gonna clear the drugs are, functioning. And We want to be monitoring our bloods regularly for neutropenia, because that's going to involve us having to delay giving our cytotoxic drugs until the neutrophil counts back to normal unless we want to give ourselves real problems. Like I say, they are more susceptible to anorexia.
We talked a little bit about ileus and vincristine. We also, there's a report of a significant amount of animals becoming anorexic on doxorubicin. And what it's not clear about is if the animals are feeling nauseous.
So Marropotin is a good idea if you think an animal is feeling nauseous, and it's very easy just to give a dose and then if the animal starts eating, you know, that was the problem. And sometimes we've used mirtazapine, to kind of encourage eating. The other thing that can happen, which probably worries the client more than it worries both the cat or the oncologist, is that they can lose their guard hairs during chemotherapy.
The most extreme version of alopecia I saw developing a cat is this cat here. This is a cat. Interestingly, we were treating for nasal lymphoma with chemotherapy.
And this was a domestic long-haired cat when we started, and you can appreciate that he's definitely lost his whiskers, but he's off, he's losing the rest of his coat as well. So I thought I'd just put a little bit about receptorizing kinase inhibitors here, just so, we're all clear what, what they are. They've been licenced in the United Kingdom for the treatment of mat cell tumours in dogs, and there's two of them.
There's one called serenib phosphate and the other is called maittinib. sucks in it, I think it is, but don't quote me on that. And basically, they act, by stopping cell proliferation.
So a normal cell, crudely speaking, will, proliferate once a growth factor has interacted with a Tyrazine kinase receptor classically on the outside of the cell. This will call this thing, basically get is transmembranous and has a dimer that gets phosphorylated within the cytoplasm of the cell, and this triggers a whole cascade of events that cause cell proliferation. So very simply, in a normal cell, no growth factor, no dimerization of the Tyrazine kinase receptor, no phosphorylation, no cell proliferation.
We know that in Marcels, tumours, not infrequently, there is a mutation, which means that yrazine kinase receptor is permanently switched on, permanently phosphor-related, and that's causing unregulated cell proliferation. So if we can switch this switch off, then we stop the cell proliferation. So A classic one in a mat cell tumour is that the growth factor is called steel factor or stem cell factor.
The receptors called kit and basically, that's what we'll see written about on the data sheets for canon mat cell tumours. So in cats, we also know, I'm just gonna move this one forward, that we have the same issue that's about half of cutaneous mast cell tumours that have been looked at in one study had a mutated kit, so that Tyrazine kinase receptor permanly phosphorylated. And if we look at cats, splenic my cell tumours, it was even higher.
And if we use a Tyrazine kinase inhibitor, so basically serinib or macitinib, then in theory should block activity. So they have been using cats off licence. However, protein losing nephropathy is reported, and azotemia associated with it and you can have the sort of expected neutropenia.
So serenib has also been associated with elevations. In ALT as well. So, be careful with the receptorizing kinase inhibitors.
They're not conventional chemotherapy and they do have some slightly less expected side effects that you would not necessarily look for, with a, with a conventional chemotherapy. So the important thing essentially is, don't equate cancer with death. Many cancers can be cured with surgery if they're caught early enough, and they can have good quality of life while living with their cancer.
If an animal bounces through your door with a lump on it, happy as Larry. You stick a needle in it, you find out that the lump is actually near plastic. That doesn't mean it suddenly had a rapid diminution of its quality of life.
It's exactly the same animal that walks through the door in the first place. So you need to kind of look past the diagnosis and, evaluate quality of life and improve it if you can, and remember, cats aren't small dogs. Any questions?
Thank you very much indeed, Sue. That's a wonderful talk. Very, very clear and logical, and took us right the way through the subject.
If you're saying that that's your first time you've done that very modestly, then I think we're all very privileged to hear it, so thank you.
