OK, thank you ever so much for looking at this webinar. My name's Owen Davis, I'm a specialist in oncology, and today I'd like to consider how we should change our practise to the use of chemotherapy and PPE in this current pandemic. We have obligations to society at large to minimise the travel of our clients and to minimise the use of personal protective equipment.

And chemotherapy treatments typically involve a lot of both. So that should produce the question, should we use chemotherapy at all? And one consideration would be, no, let's do none.

However, one thing to consider is that cancer cases in dogs and cats are very common. And if we were to say, sorry, I'm not gonna do this, then we're going to probably lose a lot of our most committed clients. Furthermore, people may look at the brachycephalic dog that's having severe difficulties breathing, and they may think, well, that dog's had all kinds of expensive and high calibre surgery.

Why can't my dog with lymphoma have treatment as well, so you can get quite a lot of resentment and feeling that the pet doesn't deserve treatment as well. More importantly, if we refuse to treat cancer cases, people will still seek advice and they'll seek advice from elsewhere. They'll often take advice from people who are not qualified to advise them, and they may end up feeding very ill-advised diets or spending lots and lots of money on supplements.

And the real tragedy of this is that treatable signs like nausea and pain will go untreated because the animal has been taken away from your care. So what I'm gonna present this morning is a compromise and the way that I'll be adapting my practise in this current pandemic. It's up to everyone to make decisions for themselves, and I'm not saying this is the way things have been done, but hopefully what I'm going to present is a justifiable solution that works for me at least.

Firstly, I'm gonna talk about mitigating the use of chemo wherever possible, and this involves evaluating the benefit that chemo, as best as possible, can bring to a case before treatment is undertaken. And secondly, where chemo is necessary to use hands-off treatments wherever possible. So I'll say from the start that what I'm gonna talk about may not be the best treatment for each case.

And in some cases it may involve using a very creative and unevaluated treatment, and I can't say that that's better than any anything else. But hopefully, this will be striking the compromise that is required. Lymphoma cases are those that require the most intensive of chemotherapy treatments, and this is where I'm gonna start, OK?

Let's start with canine lymphoma. Lots and lots of types of canine lymphoma are available. OK?

And that underlines the reason why some dogs live for a few weeks and other dogs live for a few years. So, first point then, let's find out as best as possible what type of canine lymphoma we're dealing with before we embark on treatment. First, we need to do a good clinical evaluation and decide where is the disease in the dog.

Particularly I'd like to know, is it in the lymph nodes or is it extranodal? That's very important. Secondly, we need to know what type of lymphoma as defined by the WHO histological classification.

If we put a cytological diagnosis first find out whether it's T cell or B cell with either PAR test, low cytometry, or immunocytochemistry, and then have a good chat with a clinical pathologist. Ask them which WHO category is this most likely to be. The histopathological diagnosis asks for the immunohistochemistry and classification to be applied routinely.

So for some types of lymphoid cancer like lymphoid leukaemia, primary GI lymphoma, that is cases that don't involve the lymph nodes. Primary hepatosplenic lymphoma, again just liver and spleen, not involving lymph nodes, and for the T cell lymphoblastic lymphoma. I'm probably not gonna treat them.

These guys will live for weeks to a couple of months with chemotherapy. However, the diffuse large B cell, peripheral T cell, lymphomas, the more common ones, I think are good candidates to treat. And one point here, stage does not affect treatment or prognosis.

So the stage 5 lymphomas can still experience a good prognosis and are in principle good candidates to treat. So when we're starting treatment for lymphoma, if you have an animal that is really, really ill and needs to be hospitalised, I'd recommend giving asparaginase as a subcutaneous injection. That's because it's the most fast acting lymphoma treatment and it will get that dog out of the hospital as soon as possible.

It's not a cytotoxic drug, it's an enzyme, you need to wear gloves to handle it, but you don't need the full PPE. Sadly, asparaginase in the UK is expensive at the moment, so if that's not possible, I'd give no more than 0.3 Migs per gig of dexX IV.

And provide gastro protection because it is much more ulcrogenic than prednisolone, and I'd start oral pred 48 hours later. But if we don't have a very sick dog at diagnosis, and or if we've had a sick dog that we've treated and we've made them better with the Dex or asparaginase. I would look to treat primarily with Limustine on a 3 week cycle.

And this is an oral chemotherapy drug, alongside a course of prednisolone. Now this is a a long standing all oral chemotherapy protocol for lymphoma. A lot of people know about it, it's well published and sadly it's not very good.

Lymphoma's not a forgiving disease, it needs to be treated with a combination of drugs if possible. So as an empirical suggestion that I haven't got any evidence for, but it seems to make sense, I'd look to add in a second drug in weeks 2 and weeks 3. Cyclophosphamide, another oral drug, would be a consideration, as would be chlorambil, as would be procarbazine.

Now if you'd like to do this, bear in mind it's not tried and tested and we need to manage the client's expectations accordingly. We should also have a chat with an oncologist about the best doses to use because they're gonna vary from case to case with concurrent conditions and size of the dog, etc. After 4 to 6 cycles of this treatment, if the dog's in complete remission, I'd look to change to a maintenance therapy, as I've outlined here, again, all oral drugs.

Let's go through some adverse effects we need to know about. Asparaggenase is an enzyme produced from E. Coli, so it's principal side effect is hypersensitivity.

And that's why I'd always pre-treat with steroids or antihistamines at the least. You're unlikely to get hypersensitivity the first time you use the drug in dogs, so that risk is still quite low. And on rare occasions in dogs and people it has been associated with pancreatitis and tumour lysis effect.

But these are very, very rare. With the cytotoxic drugs, well, all of them can cause a tummy upset and all of them can suppress the production of white cells and platelets. But this is to different degrees depending on the drug we've got.

With low mustine and all the oral drugs, actually the gastrointestinal signs are rare. With lousine, the level of myelosuppression is very variable, however, some dogs experience severe myelosuppression, others not so much. The principal side effect with this drug though is that it's hepatotoxic.

And the hepatotoxicity can be very severe. Normally, the insult to the liver is cumulative, but in some cases it can be idiosyncratic, so there is no dose of lousine which we would ever consider safe. To minimise the impact on the liver, we can give Sami and silliarin in products like Zentanil Advance or Denamarin, and that helps.

But that doesn't abrogate the side effects altogether. So this is an important thing we need to monitor for during treatment. The most important side effect of cyclophosphamide is sterile hemorrhagic cystitis.

And this isn't a life threatening thing, but it can be really, really painful and take ages to get better, so we need to avoid it. About 15 to 20% of dogs given cyclophosphamide every other day can get this, so we need to know about it. With praccarbazine and methotrexate, as they've recommended, gastrointestinal issues are the most common, generally they're well tolerated drugs.

And with chlorambuil it's even more well tolerated, but with prolonged use, it can cause quite a delayed and severe myelosuppression, particularly of platelets. When it comes to rescue therapy for canine lymphoma, temzolamide could be considered. Publication to support it or Eubicin, another publication here.

These are both oral drugs, but they can be expensive, hard to get hold of and certainly in the case of temzolamide, the effect is very short-lived in the order of weeks. Idalubicin is safe, but we don't know exactly what it's gonna do to lymphoma. So a better example might be if you've got them to use them in combination with other things.

Or just to use intravenous drugs. Now when we're using intravenous drugs, the ones I wouldn't want to recommend would be the vinca alkaloids or cytarabine because they're short acting. We need to go for things that will last for 3 weeks at least to mitigate the PPE use.

Doxorubicin can be considered or mitoxantro, or Tanav. And Tanavir is a new drug licenced by the FDA to treat lymphoma in the States, and it can be ordered from the company VetDC on a named patient basis in the UK. The side effects of these, doxorubicin can cause gastrointestinal effects and can also be cardiotoxic, so you need to evaluate the heart with an echo.

Mitoxantrone is mainly GI. And tannoea can cause pulmonary fibrosis, scar tissue within the lungs, and so you need to consider baseline chest X-rays and X-raying as treatment goes through. When we talk about lymphoma in cats, it's a little bit different.

I'd like to know the grade of the lymphoma to start with in the anatomic site, and that gives us a suggestion about how the disease is going to behave. For example, high grade renal lymphoma is often very, very aggressive, but intermediate grade nasal lymphoma is a much more forgiving disease. Now the histopathology and the T cell or B cell thing are much less important in cats, and I wouldn't necessarily recommend pursuing those.

The most important prognostic factor is the response to treatment. So who are the cats our treat? Well, in principle, if the owner's on board, I'd consider treating all of them, but assessing how we're getting on after a few weeks.

If we're getting partial responses where the disease is less, but not completely gone. Those guys won't live more than a few months. And I'll probably stop treating.

If we've got complete responses where the disease has evaporated, potentially these guys can live long term, many of them can live longer than a year, and I'd continue treatment. So to treat cats with lymphoma, I'd do a similar thing to dogs. I'd base it on lomustine and prednisolone.

And for cats, I would also use asparaginase if I can, subcutaneously with the 1st 4 lousine doses. That's because cats seem to develop antibodies to asparaginase much slower than dogs, and repeated use of asparaggenase has been shown to be effective. It asparaginase unfortunately is expensive, so another option would be alternating limousine and procarbazine orally like this.

Alongside Prad Again, after 4 to 6 cycles, if your cat's in complete remission are changed to oral maintenance therapy with clorabicillin pred, just like a small cell low grade gastrointestinal lymphoma in cats. Let's look at some important adverse effects. Well they mustine in cats doesn't bother the liver, however, it is nephrotoxic, so you need to check the kidneys as you go through.

The myosuppression due to lowusine can be very, very variable. For some cats, they can be extremely myelosuppressed for 5 or 6 weeks and you have to dose the drug every 6 weeks accordingly. Doesn't mean you have to stop, you just have to draw out the interval between doses.

Sterile hemorrhagic cystitis doesn't occur with cyclophosphamide in cat. Otherwise, side effects are quite similar. Rescues for cats are quite similar.

I would probably go with doxorubicin or epiubicin every 3 weeks or mitoxantrone. And when we look at the adverse effects of rescue protocols, doxorubicin isn't cardiotoxic in the cats, but it can be nephrotoxic. My Mitoxantrone again, mainly gastrointestinal.

Let's look at canine mast cell tumours here. When we think of mast cell tumours, the key thing to remember is that surgery will cure about 80%. Typically though, we can consider medical therapy for those that are metastatic, those that are high risk of metastasis.

Incomplete excised tumours, all those in your awkward locations. And in this current situation, I don't think we should be treating any mast cell tumours with drugs other than those that are metastatic or at high risk of meths. So let's consider each of these four categories in turn though, for the incompletely excised mast cell tumours, and face it, there's a lot of them aren't there?

I think we need to be asking, is it a high risk or low risk of metastasis? And to do this, we look at things like the grade, the size, the speed of growth, aspiration, lymph node status, breed, and all the well-published prognostic factors. If it's at low risk of metastasis, then a revision surgery, if we can, is best.

Radiation therapy is second best. And then afterwards I'd normally say chemotherapy can work quite well, but now. I'll just say monitor only because a large proportion of these will not recur.

It's only about 30-40% that will recur, and I think that risk is worth it in the current situation. For the mast cell tumours in locations that are not amenable to surgery, again, check is it low risk or high risk of metastasis, and if it's low risk, speak to a soft tissue surgery specialist. Surgery from our cell tumour like this was curative.

TKIs could be a second best, but bear in mind that only half mast cell tumours respond to TKIs. And those that respond respond for a finite amount of time, typically in the order of months. And when you consider the costs of TKIs, these are the very cheapest ones from an internet pharmacy in the UK about a month ago.

And the cost of monitoring tests. 10 months of TKI therapies will cost thousands of pounds. And then the TKI might stop working and you're back to square one, but thousands of pounds poorer.

So that's one of the reasons why TKIs would be suboptimal here. If we've got those mast cell tumours at high risk of metastasis. And they've been completely removed, as this one here has.

I would favour Loustine. A course of limousine is chemotherapy every 3 weeks. And again TKI's are less preferable.

Why is that? Well, the Lomustine or other chemotherapy drugs will kill cancer cells and gradually with each dose they knock down the cancer burden to 0, or we hope it's to 0. They can be used as a course.

TKI drugs. Will not affect the number of viable cancer cells very much, they just change the way the cancer cells behave so that they are less damaging. And over time the tumour will shrink because the stroma, the support network of the cancer recedes, but cancer cells still remain viable and if you stop the TKIs, the tumour can come back again.

So I think it's very important to have something to measure to demonstrate that the TKI is worth the expense and worth the risk of side effects because there is no stopping point. I'd consider a TKI for measurable mast cell tumour that is at high risk of metastasis, like this horrible one here. Lemoine could be used, but because of the liver toxicity, I'd prefer to avoid it if we can.

And this is just a picture of how this particular mast cell tumour responded to TKI drugs. With mast cell, visceral hemangiosarcoma in dogs, these guys will live 6 to 8 weeks with surgery alone. However, if you use chemotherapy, that will be extended to 5 or 6 months.

Significantly greater but never as long as we'd like. Now, there's a number of reports and a growing amount of evidence that metronomic chemotherapy, using a small dose of cyclophosphamide orally every day with paroxicam can give you the 6 months. In non-metastatic cases, OK?

Metronomic is attractive because it's cheap, it's at home, less frequent monitoring, and it's all oral. So that ticks a lot of boxes here, and this is the treatment I'll be offering for hemangiosarcomas. So it works by altering the environment of the tumour, OK, it doesn't work by killing cancer cells, it just stops the cancer acquiring a blood supply and it alters the immune system so the immune system's more likely to make an anti-cancer response.

And that's important because in principle, it can be applied to many different cancers. It's altering the environment, it's not focusing on the cancer cells, and that'll be an important point I'll come back to in a second. So peroxicam is the best established NSAID.

However, meloxicam or the coccid should be fine as well. There's evidence to say that they work, and given that they're licenced and have fewer side effects, that's what I'd go for with this dose of cyclophosphamide here. When you're giving this treatment, 15 to 20% of dogs will get sterile hemorrhagic cystitis, and that can be painful and takes ages to get better.

That's the most important side effect. To abrogate this side effect, you could consider using a similar drug, chlorambuil, at this dose here. It's less tried and tested, and particularly I'm not aware of it being significantly evaluated for hemangiosarcoma.

But there is support to say it has a beneficial effect in metronomic chemotherapy. And it doesn't involve the sterile hemorrhagic cystitis risk, so it is potentially a lower risk alternative in terms of side effects, but higher risk in terms of unproven efficacy. Now for those hemangiosarcoma cases that are metastatic at diagnosis, like this dog here.

If you use the traditional dose intense doxorubicin-based protocols, you could take away the mets. Literally, it can be a very rewarding disease to treat like this because temporarily at least you get rid of the disease burden. And the metastatic cases had similar survival times to the non-metastatic cases if you treated them with doxo.

With metronomic chemotherapy, you're just gonna stabilise the disease burden, you're not gonna get rid of any meds. So that's one disadvantage the treatment has. So for hemangiosarcomas, I'd recommend staging carefully.

You want to do an abdominal ultrasound and you want 3 of your thoracic radiographs under general anaesthesia and inflated and very carefully positioned. And for the metastatic cases, I'd counsel these clients. You can offer metronomic chemotherapy.

But the dogs may benefit more from supportive care, perhaps tranexamic acids or iron or B12 supplementation, analgesia, anti-nausea treatment, etc. Because even with the metronomic chemotherapy, they're unlikely to survive more than weeks to a couple of months. Canine osteosarcoma, bone tumours.

This is another tumour where the benefit of chemotherapy is without doubt. If you just amputate the leg, they'll live for 3 to 5 months. But with chemo as well, 10 to 14 months.

So there's no good oral option for this particular disease. I'd recommend starting by staging each case very carefully with the three view thoracic radiographs inflated under general anaesthesia, very carefully positioned. And if you find mets at diagnosis, these dogs aren't gonna live more than 3 to 4 months with chemo.

So I'm gonna consider not treating these with chemo. There's other things you can do for them though. You can consider metronomic chemotherapy as I've discussed, analgesia is very important, appetite support, omega 3 supplementation for caexia and things, short courses of antibiotics, use of bronchodilators, etc.

And hopefully that will maintain the quality of life and maintain the bond of the client with you rather than turning them away. But I don't think it's justified to treat these with chemo. For the non-surgical cases where clients refuse amputation or for orthopaedic conditions, amputation isn't appropriate, survival will be dictated by the dog's comfort levels.

OK. The dog will be put to sleep long before the Mets ever threaten the dog's welfare. So I will not treat these with chemo at the current time.

You can, instead you can do these things for the dogs, particularly hypofractionated radiation therapy involving, you know, 1 to 3, or possibly 1 to 4 radiation treatments at weekly intervals. That's a really good form of pain relief. You can also consider osteoclast inhibitors like permidronate and zoledronnate, as well as other multimodal analgesia.

So for the non-metastatic osteosarcs that have had amputation, I would use carboplatin as normally. But I'd use no more than 4 doses, and typically I would give 5 or 6 if I can. But at the moment there are publications based on 4 doses showing this is efficacious, so I've used just those.

And one thing we could consider, which is a bit experimental, is sattraplatin. Satraplatin is an oral platinum drug. And there's no evidence to say that it will work specifically in canine osteosarcoma, but initially we used to treat these guys with cisplatin.

And then we started using carboplatin, a a similar platinum drug, and we found that it worked similarly well. So I would hope from first principles that citraplatin will have some effect as well. And of course it is oral and it keeps the PPE down to a minimum.

It may be hard to get though. Now when we're dealing with bladder tumours in dogs or any kind of lower urinary tract tumour, these are diseases which are characterised by severe pain. And you can chart how well you're doing when you treat this disease by asking how comfortable is the dog, how dysuric is the dog.

Again, these guys are nearly always put to sleep due to the pain and the intractability of the pain, long before the metastatic disease causes a problem, with some exceptions, but that's the majority. So it's a horrible disease, really. Most medical therapies achieve stable disease.

But only a small proportion achieved partial responses. That's something we need to bear in mind. So, one consideration would be, is radiation therapy available for these guys, and that will vary depending on where you live and whether the local radiation centre is happy to radiate a bladder or lower urinary tract.

But often this can improve comfort. And sometimes improve urethral patency better than anything else. This is some slides of brachytherapy using an iridium wire in a canine urethra to treat the urethral obstruction there.

So radiation therapy might be my first consideration. Metronomic chemotherapy has also been used and has benefits in 70% of cases. I would use chlorambuil as a first line.

I wouldn't consider cyclophosphamide because if the dog becomes more dysuric, you don't know whether it's due to tumour progression or whether it's due to a side effect of the cyclophosphamide. So I'll use lorabil. And the majority of cases will have clinical benefits, OK, with minimum toxicity, and that will be my first line of treatment.

So I would ask, is radiation therapy or for very rare cases surgery an option? If not, I'd go with analgesia, and I'd go with metronomic chemotherapy. And I counsel a client, that may not be enough.

If you've got a very, very painful dog at diagnosis, this treatment may not cut it, and it may be worth just considering analgesia alone for those. If you need something to improve upon this and reduce the burden of disease and make the dog less painful, then blastine. Is one of the drugs that has been reported to have the highest response rate.

The highest rate of tumours shrinking, so that might be the best chance. I would probably give, you know, 1, possibly 2 doses of Elastine at the most. And if it's not working, I'd stop there.

If it's working, I'd increase the interval to every 3 weeks and then every 4 weeks. And as soon as I can, I'd get back on Metronomic chemotherapy again to minimise the use of injectable agents. And coming to the end now, just wanted to talk about anal gland tumours.

OK. These are surgical diseases if you can. And surgery alone is the most beneficial thing that we can do for these guys.

Although surgery rarely achieves a cure because most cases are slow to progress, then surgery may be all you need to get you through this pandemic situation. So if we get incomplete excision of an anal gland tumour, you could consider monitoring only. The gold standard would be radiation, if that is available.

One consideration, if you decide that a a case particularly needs medical therapy, a very advanced case in other words, could be oral mealan. The publication Here from Australia using oral mal lamb. And it's quite an easy thing to follow.

It's dosing for 5 days consecutively. And then stopping for 16 days and then starting again. So it's an ongoing 5 day course repeated every 3 weeks.

And there have been some very good survival times reported with this. For the most advanced cases where they need some form of local treatment, surgery is not possible, then bear in mind that chemotherapy in the growth setting here has demonstrated no benefit. Radiation is probably the best bet, if available.

And lastly, thyroid tumours are surgical diseases too. I'd apply the same principles as anal gland tumours. They're usually slow to progress.

If you get incomplete excision, look at radiation therapy. You could consider Taserinib, palladia, but it's actually only the minority of cases that will respond to these. Metronomic chemotherapy might be a better and cheaper consideration.

And in the incomplete excision scenario, there's this publication here out of Argentina which shows some very interesting results on using isotretinoin, a retinoid in other words, as an oral treatment after surgical excision, and they had superior survival time compared with surgery and doxorubicin. So I'd just like to leave you with some oral tumours, and this is a principle really, rather than to talk about them in any detail. The most common oral tumour in the dog is the melanoma, and we all know that this is very metastatic, and there have been attempts to develop vaccines for melanoma to control the metastasis.

Typically, if you just treat a melanoma with surgery, you'll get a survival in the order of about 7 to 15 months, something like that. But this paper here There's a large group of dogs that were treated, principally with just surgery. Very few of them had other treatments.

And they live for 2 years, surgery alone. What is different about this group of dogs, because the majority had complete excision of the tumour. So even in a metastatic disease where the mets will lead to threaten the life of the animal, you can get significant extension of life by doing a curative intent, carefully planned, aggressive surgery.

And if that's not possible, I'll just show you some pictures of myself and a colleague here. We, for nasal tumours or some hepatocellular carcinomas, thyroid tumours or for your genital tumours, we are doing intraarterial embolization where you cannulate an artery. And under fluoroscopy, you guide a special catheter into the artery that supplies the tumour, in this case a liver tumour.

And then we feed in some thrombostatic beads here, which will close off the artery and starve the tumour, the blood supply. And that, you know, referral centres that there will be techniques like this available for selected cases too. So in summary, we all have to decide where we want to lie on the spectrum between treating as normal and not treating at all during this pandemic, and it's not for me to tell you where you need to practise.

I'm just hopefully providing some thoughts as to how best you can think around this. I'd advise you to carefully evaluate the benefit that chemo may bring to each case. Think of ways of mitigating the use of chemo with more local therapy and more hands-off treatments.

Remember that this is a compromise, so we need to manage clients and their expectations very carefully. And when you're using unevaluated or kind of experimental treatments, please feel free to discuss this with your local oncologist. Thank you ever so much for listening today.