Oncology nurse clinics treating patients with lymphoma

Good evening everybody and welcome to tonight's webinar with the webinar vet. My name is Sophie McMurra, and I have the pleasure of sharing tonight's webinar. So before we go on to introduce our speaker, I'd just like to point out that tonight's webinar will just be slightly longer than expected, and for that reason, we won't have any time at the end for questions, but Nicholas kindly popped her email address onto the very last slide so that you can email in at any point if you do have any questions.

OK, so tonight we have the wonderful Nicola Reid. Nicola is the head oncology nurse at the Clinical Science and Services Department at the Queen Mother Hospital for Small Animals. She's responsible for supporting the oncology service team of nurses, clinicians, residents and students.

Today, Nicola works closely with the young. Oncology team deliver individualised medical treatment to patients diagnosed with oncology disease and support families throughout their treatment journey. She has a keen interest in improving patient access to patients with cancer through education and research.

OK, Nicola, I will hand over to you. Thank you, Sophie, for that lovely introduction. So I am going to be speaking to you today, about oncology nurse clinics, in particular, treating patients with lymphoma.

So we've got subjects within this 90-minute webinar, as Sophie mentioned earlier, I thought it was a 90 minute, but it is actually supposed to be a 60. So we're going to quite a little bit of detail this evening. So we're going to talk about what is lymphoma, how it is diagnosed and how it's treated, what happens during the average chemotherapy appointment, what adverse effects we can be, we should be looking out, what can occur for these patients when we're giving them chemotherapy, and so what kind advice do we need to provide to prepare these clients for these potential events?

And then finally, we sort of look at the way, in which a typical journey for one of these lymphoma patients might experience, and then look to the future about what's new and what's out there. We got some learning objectives because I want from this webinar as we go through it for you to understand the types of lymphoma and common treatment protocols used in oncology medicine. Therefore, then identify the essential elements to the consultation and treatment processes to, for you to safely deliver chemotherapy in your own practise.

And then from that, evaluate what resources you have to provide chemotherapy to your patient population. From that, I hope we'll be able to give you some pointers throughout this, webinar to create your own nursing proposal to become more involved with lymphoma cases and develop your own knowledge and skills even further. So what is lymphoma?

Lymphoma is actually a malignant tumour of the lymphoid system, and we know that the lymphoid system is made up of a large network of lymphatic vessels, lymphatic and lymphoid organs, and lymphatic and lymphoid tissues. There are cells that rotate around this, this network called lymphocytes, and their function is to be as part of the immune system to protect the body from infectious viruses and bacteria. Now, our lymphocytes are divided in mainly into two types.

So we've got B cell lymphocytes and T cell lymphocytes, and they are both originate in the bone marrow, but they mature, so they come. They're able to fulfil their function, with the B cells in the bone marrow and the T cells actually in the thymus. Now, their function for the B cells is to defend against viruses and bacteria that enter the blood and the lymphatic system.

And they do that by essentially having antigens on the surface of the of the cell, and they go along and sort of almost rubber stamp them to say that, they're a, infectious pathogen and need to be dealt with. After that, come along the T cells, and their job is to come, is to come along and connect with that virus because it's got the antigen placed on it by the B cells, and then destroy that pathogen. So there's a number of different types of lymphocytes.

So I've found this really, really nice sort of image set, which was fantastic to kind of explain them a little bit better. So you've got your B cells on the left, so these are the ones, as I said, that produce these highly specific antibodies. They live for a very long time and they're very important to contributing to immunological memory.

So these are the ones that really help us, essentially build up an immunity and a resistance to certain pathogens. We then got our helpers CD4 T cells, which are very highly specific as they recognise this antigen that the B cell puts on them, and they go along and produce cytokines that coordinate and adaptive immune response. So cause essentially they deal with the viral bacteria bacterial cells for the type 2s and then the type 1 helper cells will respond to the bacterial forms.

Following that, then we have our cytotoxic T cells. So again, in, in addition to recognising this antigen, they unfortunately need the CD4 T cells to help them become fully activated. And these are the ones that are responsible for cell apoptosis.

So, making cells commit suicide, when they've sort of gone, gone awry. You've then got these CD8 memory T cells, which again are long-lived cells that rapidly produce a response when they encounter their antigen. So they kind of remember when they've seen a pathogen, and therefore able to go round and target that same pathogen much quicker the second time round.

We've then got the natural killer cells, which these are properly rogue cells. They recognise the pathogens themselves and don't necessarily need the antigen from the B cells in order to be able to, Assert their effect. Now, this whole process is managed by the regulatory CD25 T cells, and they go round and manage the body's immune response, which obviously becomes aggravated in the events of a pathogen and therefore, creates this immune response to kill off the pathogen.

But then the responsibility of these regulatory T cells dampens down that immune response and calms down the body's immune system. . The only problem with this is, is that regulatory T cells can be adopted by tumour cells to protect the, the actual tumour cells from destruction by the immune system.

So they sort of kind of get coerced, and brought in or bribed, so to speak, by the tumour cells. Now all this is very relevant to what we're going to be talking about when it comes to diagnosing cancer a little bit later on. So essentially, to sum up, lymphoma is specifically refers to a group of cancers that originate in the lymphocytes, and that can happen to any of those cell lines I've just shown you.

Lymphoma can occur in any of those, so resulting in a B cell type or a T cell type lymphoma. Now, lymphoma is reported to affect between 15 and 20% of malignant tumours in dogs, and up to 30% of cancers in cats are actually cause of a form of lymphoma. But we question what actually is the cause of lymphoma.

So there's many causes that have been studied, in relation to viruses, bacteria, chemical exposure, and physical factors like strong magnetic fields, for example. Environmental factors have been demonstrated through research, to have a higher incidence of developing lymphoma, in industrial areas and areas, households which have got, exposure to chemicals, living animals, living near waste incilarators, radioactive or polluted sites as well. With regards to chemical exposure, there was a lot of evidence produced in the 1990s linking a herbicide as an increased risk for dogs developing lymphoma, but this has later been revoked following reanalysis of the original data, and this is important to be Aware of.

So while there's some things which show certain trends, as you can see from the environmental factors, some of these, papers and research studies are now getting quite old. As time progresses, it can either create a stronger link or questions and creates a weaker link. Now for us, what we've seen with our animals is that the most common association or relationship with lymphoma is due to viruses.

So this leads to a dysfunctional immune system, with especially in cats. So if FVLV and FIV positive cats do, have an overrepresented overrepresentative. level of lymphoma in these animals.

As our dogs don't suffer from similar viruses, this link between the immune system's suppression and lymphoma hasn't been clearly established yet. And for dogs in particular, it's thought that genetics, play a certain, role in this. So, in particular, you've got, Rottweilers, German shepherds, for example, can have certain development of certain cancers.

Especially with pure bird cats, there is a higher overrepresentative population of Siamese and Persian, for example, that go on to develop lymphoma. So just to round up really, the aetiology and the causes of lymphoma are currently unknown, but further investigations are ongoing in these areas to determine more of a definitive cause. For our cats with lymphoma, there are different forms.

So we have the medial stinal, which affects the organs within the chest. We have a solitary lymphoma classification, so that can occur in any anatomical location. So anywhere there is lymphoid tissue, for example, there is a a higher level of, lymphoma and solitary locations in, for example, the nose, and the nasal pharyngeal area.

Feline lymphoma is categorised into a renal category, so that obviously affecting the kidneys. And then you have an overarching alimentary form which affects the GI tract, the liver anywhere in the abdomen or local lymph nodes. And then the more common type which we think of associated with cats, which is the multicentric type, so affecting multiple lymph nodes throughout the body.

Now the occurrence and presenting signs of feline lymphoma are broken down here for you and the relationship in in relation to in with the link to viral infection. So if we start with the alimentary form of feline lymphoma, this occurs in around 50 to 70% of cases, affecting cats usually around the age of 9 to 13. This is the one form of, feline lymphoma which has the lowest relationship to a viral infection, and as little as 15% of cats in a, in a lymphoma population, were tested FELV or FIV positive.

I've listed out here as well for you, the symptoms which these animals might present with. So for the GI form for these, cats, you can have black tarry or bloody stools, weight loss, constipation, diarrhoea, lethargy, anorexia, or abdominal mass. But surprisingly, some of these animals present with no particular sign.

Their prognosis is around 8 months, but that doesn't take into consideration what grade of lymphoma they have, which I'll talk to you about in a moment. The rest of the different types of feline lymphoma, so medial, spinal, renal, solitary and multicentric, then accounts for somewhere then between the 30 and 50% of other cats with lymphoma. And it's here where those, those pure bred cats are overrepresented, in particular, the mediastinal and renal forms with the Siamesees.

So these have much stronger association with viral infection and you can see, see here from the media signal form that 80% of these cases are usually, feline leukaemia positive. These poor cats turn up on into our clinic with a cough, anorexic, weight loss. They could be open mouth breathing, and they do have unfortunately quite a poor prognosis with only 6 to 9 months and only 10% of these animals are alive after 2 years.

The renal form does have again a common link with a relationship to viral infections and again FELV and these animals often present with a form of renal failure. So we link that to anorexia, polydipsia, polyuria, vomiting, lethargy. And there on average prognosis and survival time is around 11.5 months.

But some of the solitary lymphomas, it's very difficult to list all the symptoms because obviously that depends on their physical location. But they have, found some links to solitary lymphomas and also the multicentric for cases which have feline, immunodeficiency virus positive. These animals surprisingly though, have a much longer survival time depending on where their location is.

So you can see here the solitary form, so the nasal lymphoma is 1.5 to 2.5 years and nearly 2 years for the multicentric form as well.

Unfortunately, cats know that a virus positive have a significantly lower survival time. So this takes an overarching, overarching survival prognosis time here for the line across the bottom of the table, taking into account cats that are positive versus negative as well with high grade versus low grade lymphoma. Now, as I said, we further classify these into low grade or high grade, and they are often called small cell or large cell.

And this is done via cytology, so taking a fine needle aspirate of the mass. Generally speaking, high grade is much more aggressive and associated with a poor. A prognosis, but we don't classify these these types of lymphoma any further than that.

So we don't look to see whether there are B cell lineage or T cell because the outcome is more strongly related to the disease location rather than what type of lymphocyte they are. Our low grade lymphomas in cats is often treated with just with oral steroids and, a form of oral chemotherapy, which is prednisolone and chlorambucil. Whereas our high grade lymphoma is treated using one of a number of injectable chemotherapy protocols, often involving Vincristine, doxorubicin, cytarabine, cyclophosphamides and some steroids, either altogether or, in some kind of, cocktail.

So it's fair to say that the prognosis of lymphoma depends on many different factors. So most cases of gastrointestinal lymphoma, if we're going to use that as an example for our feline cases, are actually low grade, so we would assume that most of them would do better. With treatment, approximately 70 or up to 90% of cats with low grade lymphoma will respond positively or essentially go into remission.

So, their clinical signs will be reduced. But lymphoma, throughout, for any of these animals that we talk about today is never actually truly cured. Remission is a term that we use to describe the temporary resolution of all the signs that this was making these animals unwell.

The average remission rate for low grade lymphoma is 2 to 3 years. So in the slide where I showed you the table before, there's as low as 8 years. It goes to show how aggressive a cat with high grade gastrointestinal lymphoma, does, does so badly.

So for our low grade lymphoma, it's around 2 to 3 years, which means it's a good a good thing for these cats because they may have 2 to 3 years without any signs of the disease. On the other hand, on the flip side of the coin, the high grade gastrointestinal lymphoma doesn't respond very well at all to the treatment, and only around 25% to 50% of cats with high grade lymphoma achieve any form of remission with treatment. But typically this period of remission is very short and only lasts around 2 to 9 months, and then the cats become symptomatic again.

Flipping now over to the canine form. You can see again, we have a mediastinal form, a multicentric form, so affecting all of the external lymph nodes, which we tend to be more familiar with when we're talking about canine lymphoma. There is also, in addition, a cutaneous form which affects the skin, and these animals present very, very weirdly and randomly.

It could be one isolated area or throughout the whole body. Again, they have an alimentary form, so a gastrointestinal form that affects though with dogs, just the stomach and all the intestine. And then we have the extra nodal form, so affects the eyes, for example, the bones, any of the other organs mentioned, are not mentioned so far, or the mouth.

And then as I said, the most common form which we associate with this is the multicentric form, which affects multiple lymph nodes throughout the body. So for our dogs, there's, presenting signs are obviously going to be very varied depending on where the location of their lymphoma is. But if we're talking about the multicentric form, commonly these animals present with a lymph node that could be around 3 to 10 times their normal size.

We don't consider them to be painful, but I kind of think if you have lymphoid tissue, a bit like if you've got a tonsillitis or a sore throat. So I'm sure they are very tender, even. They don't necessarily demonstrate a pain response.

When you palpate these lymph nodes, they feel firm, and rubberly, and they often move quite freely under the skin. So it's like holding a tennis ball that they swallowed or put in their sort of like gels, for example. But in general, multicentric lymphoma in dogs can also cause them to be lethargic, febrile, anorexic, weak, they might even present dehydrated.

Now some forms of lymphoma in dogs perform progress very rapidly and are life threatening without treatments, while others will progress really slowly and are managed as chronic sort of inactive diseases or grumbling diseases, so to speak. And sometimes these animals may have had their actual lymphoma for a long period of time, especially in the low grade forms or the indolent forms. But if they're left untreated, the cancer can become aggressive and lead to a very high mortality rate.

Now we subclassify our canine lymphoma again into small cell and large cells, so low grade versus high grade. But we also further classify our canine lymphoma into T cell or B cell lymphomas. Their treatment really differs depending on which subtype they are.

So if they've got a T cell, they're treated very differently to a B cell. So this is why it's so important that we actually subcategorize these animals further. A low grade lymphoma is often treated with oral steroids and chemo.

Therapy, for example, like the cats, prednisolone and chlorabasil, whereas our high grade lymphoma is treated using again, a number of different forms of chemotherapy protocols, similar to that what we mentioned with the cats or very potent oral medications, which we've got here, Lomastine and procarbazine. There is a historic thought that with the B is bad and the T is terrible. So classically they thought that T cell lymphomas were associated with a poorer prognosis.

And I've got a paper at the end of this, webinar if those of you that are particularly interested for some further reading. So prognosis and treatment is actually also linked to the lymphoma stage. So that's another thing which we can look at in order to try and predict response.

Now the staging of lymphoma, we use the staging system. So, we categorise them from 1 to 5. So one, let me just get my little wand.

So one, we'll be looking at a single node or lymphoid tissue in a single organ, for example, here we've got the submandibular node. Stage 2, a lymph nodes are one anatomical region, sorry. So kind of if you're looking around the front end of the dog here, we could classify that as a stage 2.

Then we've got a generalised lymph adenopathy, so both sides of the diaphragm. So if you've got all of their lymph nodes, they're up, for example, when we're feeding these animals with the multicentric form. And then they move into a stage 44 if their liver or spleen has been affected.

So following that, they then move into a stage 5 if they've got bone marrow infiltration or they've got a form of pleural effusion or any extranodal organ. So for example, if their heart is is affected, even if there's nowhere else affected, then there would be a stage 5. Now we stage our lymphoma patients as well further than that.

So there's a lot of organisation and categorization that we have for these to either substage A or B. Now A means they present non-clinical, so they, they may come in slightly unwell, but nothing sort of like very, very particular or they're classified as clinical. So clinical meaning that they're unwell in some way that So the difference between clinical versus non-clinical, these animals are generally unwell, so they're a sick dog.

They are, they can be cachexic. So this is where they have, sort of a form of malnutrition. So they lose weight, they lose muscle mass, they're sort of skin and bone kind of things, despite no matter how much they actually eat.

These animals can present hypercalcemic, so they have what's known as the hypercalcemia of malignancy. And, or sorry, they could be hyperglycemic as well. In addition, they may have, haematological changes, so they may be anaemic, they may be polycythemic, or they might have a hyperviscosity.

So their blood is really, really thick and sort of gooey, so to speak. And sometimes as well, these animals could be, present cushionoid. So these are all causes, sorry, symptoms of their lymphomas, which are otherwise known as paraoplastic syndromes.

And there's a lot of additional reading that you could do on that. Now this paraneoplastic syndromes are essentially in summary, a tumour associated alteration in the structure or function of an organ distant from the primary tumour site. So this could be this is often associated with the production of small molecules produced by the tumour that have an effect on a different organ.

So for example, animals that become hyperglycemic, the thought is, is that the the lymphoma tumour produces molecules that stimulate the pancreas and there Before these animals become hypoglycemic. So, unfortunately, these animals that are clinical, have a considerable amount of, likelihood to have more m, morbidity. These animals don't tend to do so well, and they live, their survival time is a lot less.

What's good though, is, their paraoplastic syndromes often resolve with tumour treatment. So this is great. So when you start the treatment, the, their hyperglycemia, their hypercalcemia, tends to resolve.

If they're cushionoid, that tends to rectify it, sweat itself as well. And that's a great thing because that kind of like treats it with everything going away. But then it's also a good thing for, the, the, caregivers and for the owners to monitor.

Because that could demonstrate a recurrence is indicative of a progression or relapse of the tumour. So if you have an animal that was presented with its lymphoma hypercalcemic, for example, and it was PUPD because of that, once it started its treatment and the, thirst and the urination drops down again, a sign that they are coming out of remission, so the cancer is coming back, could be that these animals start to drink again, drink and urinate a lot more again. So how is lymphoma diagnosed?

Now, we mentioned cytology earlier. Cytology tends to be the, the quickest and the easiest way of, identifying lymphoma. You have, a number of cells which are, proliferated away from the tumour.

You do a fine needle aspirate, you put it on a smear and send it off to the lab and you've got a good chance of hopefully getting a result from that for, for your lymphoma. At the same time, the, pathologist can actually have a look at the cells and determine whether or not they're highly aggressive. They're in large forms and very large cells, indicating that they're, highly aggressive and of the high grade form.

But the gold standard is always histopathology. So by taking a, a biopsy of the tumour, but then in doing so, The problem with that is it involves either sedation, more cost, general anaesthetics, and all these things come at a risk. So how do we subcategorize our lymphomas to identify whether or not they're a B cell or a T cell, for example, or even if we don't get a result on the cytology, there are a couple of methods that we can use.

Now, I'm only really going to talk about immuno phenotype pin and par in these next few slides. So immuno phenotyping is done by flow sorry, flow cytometry, and it's a method of measuring the number of cells in a sample. So the percentage of live cells in the sample and certain characteristics of cells and what we do is we're looking at their size, shape, and their presence of tumour markers on the cell surface.

The cells are essentially stained with a light sensitive dye, placed in a fluid and then passed through a stream before a laser or other type of light. And then these measurements are then counted and based on how light sensitive the dye reacts to the light. So flow cytometry is actually a really important tool for the diagnosis and management of certain tumours such as leukaemia and lymphoma, and it really helps us to find the lymphoma subtype together with the cell morphology.

So here's an image essentially of what happens. So we use either blood or tissue, which we've got from a lymph node, . It's got a very, very high sensitivity and can detect a lymphoma cell of like 1 in 10,000 normal cells.

And it, by actually having this test, it allows us to help with the treatment plan and and the likely biological response. So you can see here what happens is, is the sample goes through here, it gets each cells get sent out in a single file, and as they're going through, they are. Stained.

So it goes through. So if these the red ones, for example, if we thought that these were the lymphoma cells in amongst all the normal lymphoid tissue from that cell sample, or there might be red cells and contaminating the sample, for example, as they go through, when it, the laser light beams through, the light is refracted off of the stain cells and therefore we can detect the, the lymphoma ones within the sample. In human medicine, they use it as a marker of treatment response as well.

So how many of these cells, because they are all counted of how many are sending off these refracted stained, light, so to speak, and it really helps, regularly in human medicine to determine whether or not the, a person is having a good response and how, what their level of cancer they have in their blood. Or lymph noid and this is the kind of result that we'll probably get back from the lab. So we talked earlier just briefly on all the different types of, lymphoids, lymphocyte cells.

So here they all here. And then so they send them off and as it goes through the machine, these are all different stains that they have. So you can see here that CD45 is has an antigen.

If they're positive, it means The cells that they're counting are a leukocyte. So on our flow cytometry, we've got here that the leukocytes came the cells were positive, meaning that our sample was of lymphoid tissue. For example, if you're doing an abdominal mass and they weren't sure whether it was lymphoid tissue or it was something else, then it goes to show here that actually the sample that we got had lymphoid tissue in because it's stained for CD 45.

We then look through and the cells have stayed negative for CD3, CD4, so these are all biomarker stains. CD 5 is negative, CD 8 as well. But look here, we've got CD 21, which is positive, which is a biomarker for.

B lymphocytes and 79 as well. So these two are positive, indicating down the bottom here that flow cytometry, this animal samples were stained with CD 21 and CD 79 indicating a B cell lymphoma. Now, this is interpreted as well as the cytological findings because they, these tests are never a standalone test, and it's saying that these have really large cells, 2 to 3 times the size of a normal lymphocyte.

So the interpretation is that it's a very diffuse, there's a high population of cells because it says up here high harvest, of diffuse large B cell lymphoma. So that's how to read your flow cytometry results. As you can see here, I miss the spinny bits.

The thing is with our flow cytometry samples is is that you must have live cells for this to work. If the cells aren't live, then they won't pick up the staining. And so you need to make sure that the cells are preserved as best possible.

Now, to do so, you make a homemade so medium. And you take 1 to 2 mLs of the patient's EDTA, spin that down, so separating the, the red cells from the EDTA in the, in the plasma, and then using the pipette, you collect the EDT plasma and put that into a fresh EDTA tube. From that, you then dilute it 1 to 1.

So if you've got say 0.5 mL of plasma, then you want 0.5 mL of EDTA, and then that is your concoction.

From that, after you've taken your lymph node sample, you're spraying it into very gently into your concoction so you can syringe it in and out through the needle in order to suspend the cells. It's important as well, as we want this to be a live sample, that the cells are handled as gently as possible. One thing to do is to, if possible, avoid submandibular lymph nodes.

This is because, if you've got, if you think a lot of animals that are presented with cancer may be slightly older, they might have dental disease and so you could have, even if it is a, a, there's lymphoma. Infiltration into the submandibular lymph nodes. The problem is, is that there's a possibility that there's infection in that local area because of dental disease and you'll find it harder to actually get, a diagnostic sample.

So whenever you're doing cytology for lymphoma cases and you've got a different, or, another lymph node that you can actually aspirate, we always recommend that you go for those. Be very gentle in your sampling as well. Lymph, lymphocytes, exfoliate really, really easy from the, from the lymph nodes.

So essentially, you should be really gentle in, hand in handling with the needle technique and then spraying them onto the onto the slide. We recommend that you use a needle only technique, so not put in the suction on the syringe at the other end because these cells proliferate so nicely and use narrow needles as well, purely for the reason that if you've got a very highly active lymph node, there is a possibility that it may bleed. Even if it's a little bit, but what the problem is, is that that will contaminate or your slide or your sample because you're hemo diluting it.

So you'll put in red blood cells mixed with the lymphocyte cells, and therefore causing a, a more of a challenge for your pathologist to interpret. And then obviously be very gentle with your smearing because you don't want to squash these cells and spread them all over the place. You're just gently smearing.

What we recommend as well, which is a great skill to have, is to check your in-house cytology yourself first to make sure that the animal's got, a diagnostic quality sample. So, if you have 234 slides of your fine needle aspirate, take one of them. We recommend the worst one because then everything else should be better.

Staining it yourself and look under the microscope and you want to be looking for intact cells. So if you've got a nice population of intact cells, the cells with a clear cell membrane, and nucleus, like obviously, large populations of them, then it's a sample of diagnostic quality. An additional test as well for diagnosing lymphoma is a PCR for antigen receptor gene rearrangements or otherwise known as PA.

Now this is a clonality essay, which helps determine cancer versus inflammation and lymphoma. Now that is done, we use this test, sometimes when we've got a problem with this, with our cytology sample. Now, I'm sure we've all seen when we've had, cytology results come back from the lab and it says, they have a list of differentials because the population is difficult to interpret.

So it may be inflammation versus neoplasia. So essentially the results are inconclusive. It may also be the only option when a fresh sample cannot be obtained.

So the animal's gone home and we need to do further testing. So if your cytology sample comes back and then I'm in an RA whether or not it could potentially be lymp lymphoma, then you can send that sample off the path. .

The difference is, is that it is a sensitive test, but some texts suggests that it has a sensitivity as low as 70%. So that's why mostly flow cytometry is, is the, test of choice. However, it does depend whether or not you can get a fresh sample or you had a fresh sample in the first place.

And it's designed again like flow cytometry to complement cytology, and it's not a standalone test. Now, it works by using DNA. So it's actually extracting and looking at the DNA within the cells to see where that where that cell lineage comes from.

So a positive clonal result can then be identified to see whether or not these animals are T cell or B cell in origin. I explained this better in the next slide with a picture. So a single cell line, if you have, when you do PA and you've got a single cell line, and a large population of cells, and they all come from the same place, it means one of the cell lines went awry.

So one of them is essentially, I think of it like a mother ship. The mothership could create like the two daughter cells and so on and so forth. So it's likely that this is a neoplastic, population of cells.

This is the opposite to what's happened here, which is a polyclonal result because, and which is often seen in a in inflammation or an infectious process and it's the bone marrow's response because remember that our lymphocytes originate from the bone marrow. So this would have come from that point. So then you have literally lots of different cell lines creating lots of different populations.

So you've got a very polyclonal population, meaning that there's lots of different cell lines. So it's unlikely they've come from one mothership because there's lots of different processes happening. So a PCR result might look something like this.

So this is a polyclonal population. So lots of different cell lines, so that's what these peaks are here. So demonstrating inflammation or an infectious process versus a monoclonal population.

So you've got a very high number of cells of one genetic line. Which would be a new plastic. So moving on, hopefully that's given you a good understanding of what lymphoma is, where it comes about, and how we test to find out, to get a different, a definite diagnosis and also the subcategorization of them.

So we're going to go into goals and treatments of lymphoma. So factors that affect the different treatment choices, the frequently used protocols and potential response rates to those. Now our goals are essentially to induce remission for these patients and alleviate clinical signs.

We want to improve their quality of life, and by that we do that by managing adverse effects. And throughout the entire process, obviously we need to be supporting us, not just the animal, the owner and the family as well throughout this journey. Now there's two different ways of looking at what we use for protocols for lymphoma.

There are the single agent therapies, which are a much lower cost usually. They tend to be less toxic because you're using one drug, and not a combination of different drugs. These animals are rarely hospitalised.

However, the problem is, is that these drugs tend to become less affected, the less effective. And this is because it leads to chemotherapy resistance. So if you've got one drug, I think of cancer like a virus, essentially.

So you have a, a virus which basically gets clever. It's the same as, bacterial resistance when you're exposing the same bacteria to the same, Antibiotic all the time. So this is, you know, a, a buzz thing and press at the moment still about, multi-drug resistance with, using far too many antibiotics.

I think of cancer in exactly the same way. So if you're, exposing the cancer to the same drug as, as, as the single same drug over and over again, that cancer is going to become clever and therefore become resistant. However, single agent therapy may be the only, affordable choice for the owner, or the owner might be concerned about toxicity, or they might not have a lot of money in case something goes wrong.

So this might be a reason why single agent therapy is adopted. This is the opposite sent to multi-agent therapy, which comes at much higher cost because you're using different combinations. Animals need to come back to the hospital regularly for regular tests to make sure that they're not having significant myelosuppression by having all these different drugs.

And therefore they do have a higher risk of toxicity because you're sort of attacking the cancer with different drugs at different times and so hopefully outwitting the cancer and therefore having a prolonged effect. And so chemotherapy resistance or the development of resistance to the chemotherapy drugs is much slower, therefore making the whole thing much more effective. However, there's many factors that may influence the choice of protocol.

We mentioned cost. Chemotherapy drugs are expensive. They're single use only, so you, draw up the drug.

A lot of them are larger vials because they're used in human medicine, so you do throw a little bit away. Yes, obviously the patient's behaviour you need to have to take into account as well. You might have animals which are very nervous, they might not travel well.

So you don't want to be, you know, putting all your eggs in one basket and saying that this is the best protocol for the animal, if the whole quality of life associated with their visits is compromised. I've put beliefs here, and there are various different interpretations of what beliefs are. You could be thinking that, beliefs in relation to a religious, familial, upbringing.

That does come into account. There are some religions which, animals will be treated in a, in a, and seen in a much higher level within their, their family, so to speak. You've also got different beliefs in relation to whether or not a client has any preconceptions about what cancer is and, and chemotherapy treatment.

For example, They associate if the, the treatment that you're gonna give to the animal is gonna induce the same amount of sickness that it would in a person, which isn't necessarily true. On the, again, the number of visits, it could be not just because of the patient travelling, the patient might travel really well, but these clients also have like lives and families themselves that they have to organise around. Having their pet come in for weekly visits for chemotherapy may be challenging if they live far away from the practise or they have a job which they can't get time off from.

So that may influence the choice of protocol as well. Now some of these drugs from time to time, obviously they are human medicines, and there are challenges in getting hold of them. There's also some challenges with regards to, whether or not, not only they're available from whole wholesalers or from local hospitals, that's also a challenge sometimes.

And also, if you can get hold of them and you can store them safely. And handle them effectively as well. So some, there are some practises who are still a little bit shy or uncertain about getting these drugs in, and or how to administer them safely, which then affects the, the choice of protocol available to them, to the owners.

Now there are some more famous protocols which I'm just going to run through with you here. So we've got the high grade lymphoma protocol B cell lymphoma protocol, which is more commonly known as COPP. So this is a combination of cyclophosphamide, doc.

Rubin being Christine and prednisolone. Prednisolone is only given for the 1st 4 weeks. And then these, these drugs are given in combination on a weekly basis.

And they have what's known as regular cycles. So they go in a certain order and they cycle around them. Sometimes these animals start off because they're particularly sick, so these might be our clinical cases, so our substage B type animals, which they get sort of, they get an induction with asparaggenase at the beginning or it can be used as a rescue throughout.

So when we treat these animals with our top protocol, we tend to have a 90%. Response rate. This is in dogs.

With 50% of those dogs actually surviving with their lymphoma of a high grade form for up to 12 months. Now 20% of those dogs, so we're now talking 10% in the first place, of those, only 20% of those survived for the 2 for 2 years. And unfortunately, a survival rate is 5 dogs in every 1000 will survive, 2 years or more.

But then if you think about it, these are animals which are going to be have in going through stages of having complete remission. So demonstrating no clinical signs of their disease. So having a positive response rate in the first place is a great thing when using this protocol together.

I've listed out chop here just as an image, just so it's an extract from the, newest edition of Withrow, which is like the oncologist Bible. And just list out for you, you can see. So each week something gets done to the animal.

So it involves a huge amount of commitment from the client and also organisation in the practise. There's a number of variations of this protocol that have been explored, including reducing it just down to 12 weeks, 19 hour or the full 25 weeks. But what's important is animals need to have a CBC before each chemotherapy, and they have to have any delays in these treatments as well if their neutrophil count is less than 15,000.

At the end of treatment, these patients are then observed for relapse. So they have their 2025 week or an example here, I've changed it now so that you can see that, it's a less, it's still the same protocol, but it's sort of condensed down to 19 weeks rather than the 24 from before. At the end of the treatment, as I say, these patients are observed for a relapse.

So they're basically, they have this massive intensive protocol, and then, most clinicians will just stop them. Some clinicians will place these animals onto a maintenance protocol of, say, for example, chlorabil or just keep up with the cyclophosphamide. And then when this patient relapses, I've put if stroke when, but it is unfortunately usually when the cycle started again.

If that patient then fails to respond to that to that protocol again, that's when they, when we look at, doing something known as rescue therapy, which I'll go on to in a little bit. Now for our cats, we do use chop as well, but we do do, we do embroil that as a 25 week protocol rather than trying to condense it into the 19 week or 12 week. And again, at the end of treatment, patients are observed for a relapse and some are put onto a maintenance protocol usually of loamacil.

And again, patients are, that relapse, we then look at a rescue proto protocol. So unfortunately, like I said, with the whole chemo resistance thing, the feline high grade lymphomas, we looked before, if we remember to the beginning of the presentation, these animals only, survive for 2 to 9 months. Once this patient relapses, unfortunately, this is the reason why, because the rescue protocols are often futile.

So it, the cancer. Has already developed chemo resistance and reintroducing those drugs unfortunately don't work. So if you think about it, 25 weeks is a really intense protocol for a cat.

Many of them do do well, but sometimes, unfortunately, you have to change or adapt what you're doing depending on the patient's behaviour and how well they're coping. And obviously they have a very highly aggressive form of cancer. And if that's, if you're managing to push them all the way into remission.

So instead, cats tend to have, a cop protocol, which is, it is still an intense protocol, but it's a 4 to 6 month protocol. And at the end of these treatments, these patients are put on again a maintenance protocol of chloramasil or cyclophosamide. You can see on the right, a table of what the COP protocol actually requires.

So they have cyclophosphamide given 3 weeks on the day after Vincristine. So they have Vincristine given on weeks 123, and 4. So they have weekly treatments, and then they have it every 3 weeks.

So, it's a much less intensive protocol, and these patients do arguably do as equally well as the CO protocol. And then what you've done is you've held your doxorubicin back, and so, if these animals relapse, the rescue protocol, the first line is usually the doxorubicin, if all other attempt, however, then are thereafter, all other attempts again are futile. For our T cell lymphomas, so we tend to use what's known as a locker protocol.

So our cooking pot for that is Lomastine, vincristine, prednisolone, and procarbazine. And again, these animals, if they are particularly sick at the beginning, we used the drug called Lspirogenase. We'll see for our dogs, so, for T cell because we don't immuno phenotype our cats.

So we have a 90% response rate for those. And of those of 100% of dogs, 39% of them will actually survive up to 12 months. So less than the B cell lymphomas.

However, interestingly, 25% of the total. Dogs. So it was only 10%, wasn't it, for the B cell lymphomas.

25% of the total dogs that, start this protocol will survive for, up to, will survive at 24 months. And thereafter, approximately 10% of them survive for 3 years or more. So the whole B is bad, T is terrible, tends to not quite be so bang on anymore.

What does the LO protocol involve? So it's a 14-day cycle repeated 6 times. And most importantly, we need to be careful with liver toxicity because the drug is, I've forgotten the word.

The, the drug is essentially, processed. I want a more scientific word for that, by the bladder, by the bladder. I'm getting all my, my tongue twisted now.

The drug is metabolised, that's the scientific word, by the liver and actually can cause some toxicity to the liver as well. And unfortunately, that it tends to be the main reason why Lomastine is the drug which is stopped or the treatment is changed. So, as well as checking these animals CBC every single time they come in, there is also keep an eye on their liver, especially for the first few doses.

Again, at the end of the lot protocol, similar to the ch protocol at the end, the, of, of the process, the animals are observed for a relapse. And interestingly enough, the average disease free interval, that, that means the time that they remain in remission from the, from the, start of their protocol is 176 days. Now, rescue protocols, are to repeat the lop.

So if when they come out of remission. They look to repeat the lop, but again, due to chemo resistance, this may not work and so other drugs might be introduced, for example, doxorubicin, epiubicin, and chlorambail. Now, even though we've gone through some some numbers, and some likely predicted responses, we need to be mindful that different individuals can still respond very uniquely to different treatments.

And one thing to remember is the breed considerations in in relation to multi-drug resistant genes, so MDR ones. These are dogs that carry a mutation actually. On the cell membrane.

So you've got these pumps that pump out drug out of the cells. So if you imagine giving a drug to an animal, it goes into their system, it gets into all their cells, and then you've got these special pumps that line the the membrane of the membrane of the cell and pumps those drugs out. So it's easier to metabolise out of the body.

Unfortunately, Dogs that have an MDR1 mutation, lack this pump or lack a a a high number of this pump, and therefore they're unable to get the drug out of the cells. So the cell, the drug has a much more toxic effect. So there are animals that will respond very differently to some of these drugs and can potentially have adverse effects or become sicker.

In particular, the drugs that we use in our CO protocol, so the doxorubicin and the vincristine. So if you have any animals which you're going to start on their chop protocols, it is worthwhile having these animals tested. So we're talking collies, Australian shepherds, Shelties, border collies, long haired whippers, old English sheepdogs, for example.

And this is done as a PCR test, so saliva or blood is sent, to external laboratories. The other thing is, is that tumours behave in very in different ways. No two people like essentially are genetically identical.

And so they two tumours, even though you might have two dogs from the same family, they might not have two identical tumours that, behave in the same way. So each animal's biological makeup will make, will determine a unique response to that treatment. So just because one's responded in an expected way doesn't mean to say the other way.

So we go into the real crux of it now. I just have another sig of water. As to what our chemotherapy clinic essentials are.

So what are the core elements needed within the practise to deliver these, these, treatments safely? So essentially, we do need some space. So we need a consult room.

We want, to be able to, time our consultation so that we have an appropriate amount of time for them. We need, to be able to hospitalise these animal and find a suitable area with adequate ventilation in order to provide these treatments and give the actual chemotherapy. We need some particular facilities if we're going to give chemotherapy in practise.

So bedside laboratory equipment, so, complete blood count is, is needed. So either access directly to one of these machines or, somewhere locally where you can get it done quickly the same day. It's really handy to have a microscope as well, so to do platelet check.

White blood cell checks, cytology, for example, have a centrifuge to do your PCV and then any chemistry, analysis, your analysis. All of these are necessary to evaluate not only the response to treatment, but also assess for the chemotherapy induced my suppression or any infectious processes and drug specific toxicities. We talk about supplies as well.

So we mentioned before about how sometimes we can have challenges in getting the drugs, but once they're, you've got them in your, you've got them in stock, you need to make sure that you've got safe storage for these because they are actually classified as hazardous drugs by the health and safety, executives. So they In theory should be under lock and key, but there's no regulations to say that you have to. It just, they just need to be in a safe space away from people who could abuse them or get to them, so to speak.

So obviously you'll have them out the back or in your in-house laboratory somewhere, not necessarily a fridge or a dedicated place under lock and key, but somewhere where you just have people there who you know that you can trust and then, they're not going to cause any harm to anybody. That they're somewhere safe, they're somewhere secure. If they did it, they're not going to just fall off a shelf, by accident, that kind of thing.

. You therefore also need to consider safe techniques. So, the best thing to be using with these cases is lower lock syringes. So you can screw your syringes onto, onto the actual giving sets in whichever way you're administering them.

And there's a hard push now for using closed system transfer devices. So, an image on the left is actually the far seal system. So it's a method in which the drugs are removed from the vial without creating any form of aerosolization.

In addition to that, there are, online pharmacy, so to speak. There are, there, who which have been set up to deliver chemotherapy and pre-prepared syringes as well. So, I'm not gonna mention any in particular because, I just, I suppose I shouldn't, but if you just Googled it as a veterinary, pharmacy who will, give you, supply you with chemotherapy, you can already have all the drugs drawn up and ready to go for you as well.

And they provide, all the bits for the closed system transfer device in order to make it much safer. Finally, going on to PPE. So this is a completely and I see most definitely essential element to, administering chemotherapy.

You, I hope you can appreciate from all these different images that they are all taking a slightly different approach, depending on the level of, a high level of biosecurity you have with administering your chemotherapy and your, if you have closed system transfer devices for the administration. Again, this is for seal being used down here. This gentleman seems very happy, holding his dog, whether he was getting ready just prior to giving chemotherapy is not fully dressed, I'm not sure.

But he's, he's just got a, gloves on and he's got the gown on. Then you have these ladies up here who's giving chemotherapy again with the gloves and the gown, and note that they've got goggles and, just the standard surgical mask. This, these colleagues over here on the right, again, giving chemotherapy.

Note the gloves and the gowns, but just a face shield, so which covers up all the way down to the, sort of like chin level. And then I hope you can appreciate it from this picture again, just taking it up another notch is these people have actually got, carbon filtered masks as well. So taking it up another level.

Now, it really does depend on what kind of trans administration device you use as to what level of chemotherapy protection you use. But the American College of Internal Medicine have a have a really, really good, reading list of what to do with regards to safety techniques and things like that. It's something which I would encourage you to look into.

It's a really good review. I think it's dated 2018, if not 2019, and it gives a much more up to date of what is advised and how to improve safety within your practise. Oops, I can't stress it anymore than it's essential.

So what happens with the chemotherapy appointment process? So essentially you are consulting with the client, the animal has a basic examination, they're sampled, and then they're settled into their kennel to await the results. So, we as nurses, we can run the test and document the findings.

Then there is a case discussion with the care team, see how the animal's doing before they're prescribed the treatment, so the chemotherapy. Drug doses are calculated and the drugs are then prepared and administered. Any medications are also prepared as well as their discharge instructions.

And then these animals have follow-up appointments arranged. They're fed and they're toileted and then they're discharged. Now for us as nurses, I think it's, it's quite prevalent that we can be highly involved with these and take the lead.

So, For example, we can consult with the client. We can do a basic examination on these animals. We can sample them, we can settle them into a kennel.

We can run all the tests. We know how to run a CBC if we've got, if we're monitoring other things like urinalysis or renal values, for example, or liver values, then we can do this and document the findings and we can have a discussion with the clinician about what our findings are, how, how that feelings was with the consultation with the client. Obviously, we can't prescribe the drug treatment, but we definitely can calculate the drug doses.

It's no different to a vet prescribing 20 mg per kg of amoxicillin, for example, as long as you do it in a thorough and a, and a safe way. We can prepare and administer the drugs as well. But of course we can't prescribe the medications that they need to go home with, but we can contribute to preparing the discharge reports and the discharge instructions, and we can certainly follow up on appointments and feed and toilet the patient and discharge the patient and communicate with the client.

So overall, out of all the things that are actually involved with a chemotherapy appointment, there's a lot that we can take charge of and do. Now just to note about what we're doing when we're having a consultation with these clients when these animals come back and forth with us, the, what we are doing is we're having a clinical evaluation of the whole situation every single time. And we are looking at what these animals' response to treatment was.

So once it had the chemotherapy last time, it left the hospital or the practise, and so what's happened since, that animal received its treatment. So have any of the physical signs or the clinical signs, changed since they were, since they were administered the drug? How's the animal's general well-being been?

And did these meet the owner's expectations? We then we do that by questioning and answering any questions from our clients and we can address them, any concerns that do pop up. And most importantly, during this consultation process, we're evaluating how that animal has been for the last week, 2 weeks, 3 weeks, however, it was long since they were seen.

So did they have any adverse effects to their chemotherapy? What was expected? What were they and where they expected?

How severe were they? Did they need any supportive care? And did they have a, what were the number of bad days that they had?

So if you have an animal that, I'm just gonna pick one out of the sky that had been Christine over a week ago, they've had really, really severe nausea and anorexia for 5 of those days. Like the, the number of bad days outweigh the good days. And so what effect not only did that have on the animal, but what did it have on the owner?

So taking it back to the right hand spinny or circle that we had were these owners' expectations? Did they think, you know, that was normal because it actually isn't normal. We give chemotherapy to animals at a much lower dose, anywhere really less than half of what, half of the dose of what we give to people.

So the adverse effects should be significantly lower. Once we've done all that and we've summarised how the animal's been, so hopefully had a positive response to treatment with minimal adverse effects, we then can confirm the ongoing treatment plan, with, with the owner and with the veterinarian. These animals, when we talk about evaluate in response to treatment, we talk about complete remission, partial remission, stable disease, or progressive disease.

So if we're talking about our lymphoma cases, let's talk about a, a dog with multicentric lymphoma, and when you saw it last time and you gave it its first dose of incristine. Has it had a complete response? So are the lymph nodes normal now?

Do they feel normal? Do they measure normal? Or have they had a partial response in which they have shrunk, but not, not as much as we had hoped or anticipated, or is the disease stable?

So is everything exactly the same? Because if it's the same, we may need to change things up. .

Assessing these patients for chemotherapy induced my suppression is what we must do at each of these visits. And so they need to have that done by running a complete blood count. And that's when we said earlier by having all the different things like a microscope, blood count, analyzer, all of these bits are really Useful.

So when we're assessing them, we're not only assessing them for their my suppression, it's whether or not they have any infectious process is brought about by the fact that they've been immunosuppressed due to their chemotherapy and any drug specific toxicities we mentioned obviously with the Lomasine earlier. So what happens with, when we talk about chemotherapy and introduce myosuppression. So, we know that ythrocytes last much longer in the circulation than our platelets, and our neutrophils last the the shortest amount of time.

And so what happens when, animals have chemotherapy, it inhibits. It's the bone marrow from producing the white blood cells or destroys the white blood cells that are already in the circulation or the bone marrow, so causes what's known as neutropenia. This is when the bone marrow is therefore not able to make any or enough neutrophils or when the neutrophils are destroyed at a faster rate than they have been produced.

And this is the way, and I'll show you an image to make hopefully make this more explanatory. I think if you look at the top right, I think of the bone marrow as a tree. So the tree gets all its nutrients from the ground, so the body produces, so you've got the buds at the end of the bone.

So if you imagine this being a bone, if you kind of think of it in that kind of shape. So all of the nutrients that are needed are growing, growing, growing, all these buds. Grow, grow, grow, grow, grow, and they get to the end of the branch and then they drop off.

So the leaves drop off into the circulation as a neutrophil will drop off of the end of the bone marrow buds. So they go off to go and be useful. And there's lots, as you can see, they're all there ready.

They're all nice and mature, ready to drop off at the appropriate time when they've matured and they're ready to go. What happens when an animal receives chemotherapy is they get almost like a sharp frost. So suddenly, all of these mature leaves that were sitting in the branches drop off.

And so they, they, you see a surge in the bone, in the, neutrophil count initially on giving chemotherapy. All of the neutrophils have just dropped off. Those that haven't dropped off have died, and then so they're no good.

And so it takes a while, but it does happen and within 7 days on average, the bone marrow regenerates itself and there we are, the leaves come into the edges of the bone marrow buds ready to do their job again. So this is what happens here. So if you can imagine, it's kind of like, so this is where the chemotherapy gets given.

All of the, neutrophils get released into the bone marrow, and then they're used up, used up, used up, used up, used up. So this is where they're growing, having to, they're not actually being released by the bone marrow because they're still having to grow and then eventually We're at this point here, so they're the lowest possible. So they've all been used up in the circulation, so you can't see any line around here, but they're just about to be ready again.

So then this is when the numbers increase again. I hope that makes sense. So this point here is that is known as the nadir or where these animals are most at risk.

So what is the Nadir? So this is the time point when the chemotherapy drug has had its greatest effect on the circulating counts. So for most chemotherapy agents, the Nadir is around 7 days post administration, and this is why it's recommended that a complete blood count is repeated at this time.

Now different drugs at, than Nadir happens at different times, but it tends to be around the 7 day mark and I've listed some of them here. So you do need to be careful about whether or when they're actually having their Nadir, but it tends to be 7 days. So we kind of think of that this is being the point at which these animals are at most risk or vulnerable.

Now, dear curves, so this is a blood samples taken from the same patient over a number of different treatment cycles, so all the different dots. So you can see that this patient has had different responses each time. Before it's had its, been Christine each time.

So one time it had it and it didn't drop below 2.5. Another time it dropped all the way as low as, just over 1 here.

So an individual can have a different response each week and that's why we check them each week. So the question is, is when you actually treat them? So if we think that a neutrophil count should be over 2.5, it's whether or not they're treated at 2.5 or above, or we want to make sure that they've got more or we're happy to treat them at 1.5 or above.

Question is, is that what we saw when we looked at the COC protocol before, if the neutrophil count is more than 15 15,000, then they will be treated. So then we grade them for their neutrophil count, as, in the way that is on this table here. And let me quickly go through the first two grades.

So the neutrophil count is, anywhere between 1.5 up to the normal of 2.5, and they have a very, very low risk of anything going wrong.

And so that antibiotic treatment will tend to be numb. We won't cover them with antibiotics, and they will be treated, so they will get their next dose of chemotherapy. A grade 2 means they're less than 1.5.

And so they won't be treated. And so these animals will be asked to return again in 3 days and usually their neutrophil count has returned to normal and so they then can have their treatment. We don't actually give them any antibiotic cover.

We do prescribe it, but we ask the owners to hold on to it. And they monitor the animals at home for the next 24 to 48 hours. And if they're symptomatic or they, become clinically unwell, then we ask them to start their antibiotics, if they're priororexic as well.

If a patient at any point does have a fever and they're lower than a normal neutrophil count, regardless of the grade, we do treat them with antibiotics. And the antibiotic of choice is amoxic 20 mg per kg twice a day for 5 days. And the reason why, we cover them with antibiotics.

Is because if they don't have enough neutrophil circulating and they have a fever, it shows that the animal has likely got to have an infectious process and they don't have a high enough level of immunity in order to fight it off themselves. So we look to cover them with antibiotics. So if everything is going straightforward and we've done the consultation process and everything's OK, the animals in remission and we've done their blood sample and everything's looking normal and they've got a neutrophil count of over 15,000.

We'll go ahead and we'll give them their, calculate their chemotherapy. Now, I've, we've got this, sheet that we use here. I've shared it many times with many different, oncology nurse communities because we find that it's really helpful and it works well.

So I'm more than happy for you to utilise it in your own practises as well. What it does is it lists all the patient information, and you are able to have a direct conversation with the clinician, sorry, a direct conversation conversion, sorry, conversation. From kilogramme to metre squared, and it includes if these patients are treated for a lean body weight.

So, it's like going back to school where you got told all the time to, all, complete, all your workings out. So you got a point for that as well. So our animals are dosed as, mixs per metre squared, mostly for the drugs that we've been talking about today, but not all of them.

So this would be something which your, clinician would prescribe. They'll say, so you can have your weight. So for example, you'd have your 10 kg here, converted it into 1 metre squared, and then you would have it your dose.

So if we're dosing something, for 2, you would then times your 1 metre squared times your dose, which will give you your answer, and then divide it by the concentration of the drug, which gives you your total volume of, Meals. So you're able to physically check before someone else is able to physically check the volume in your syringe before that's given to the animal as well. It allows for one person to check it.

It allows for somebody else to doubly check it as well, and also check against the last dose. So we note down here what our last dose was in meals. So we can have a look because if when we gave them 0.5 mLs, for example, last week have been Christine.

If we've calculated it at 0.6 mils, that's what, 20% increase. So we can go back and make sure that was there a problem with the weight this time round, where they do for lean body weight because they're slightly overweight.

So it's always checking that you're given in a similar volume and if not, you're investigating the the the reason why. This allows us to keep a good check in the 5 rights. So checking, probably checking the, the date and they're OK to treat, so the correct time for the drug, checking the right patient because we've got all our patient details here and hopefully you're using name tags in practise, checking the right drug because the drug's here, checking the right route, we check off how it's given and we check the right volume.

So, and it also helps us with complete record keeping as well. So everybody happy. Before we go ahead and give them chemotherapy though, we have to consider chemotherapy induced nausea and vomiting.

So many chemotherapy drugs are known to be emetic agents, which are caused by stimulation of the chemoreceptor trigger zone and the the postrema of the medulla. And this is sensitive to bloodborne substances or otherwise known as, otherwise, chemotherapy. So I find that quite easy to remember.

Now, you can also be stimulated by the affra receptors located in the visceral organs including the gastrointestinal chat, pancreas, liver, and the peritoneum as well. Oh, sorry, that's the wrong one. That should have been in that one.

And then finally the neural impulse is sent into the vomiting centre in the medulla, which is the one on the bottom right. So. We pre-medicate our patients prior to chemotherapy with most of the drugs we use, as a first line, and we use the NK one antagonist, which, is the, the, oh, Mirropotent, sorry.

We pre-medicate them at 0.5 mg to 1 mg per kg for cats, 1 mg per kg for dogs, and that's given IV or 2 mg per kg orally at home before they actually have their treatment or they travel because that helps with that as well. And then these patients are sent home with 2 to 4 days' worth of treatment to be given with advice to the owner to treat as necessary.

Now the reason why we have to use the Meropotent first is because it's the licenced drug to use. And the idea is, is that as it's promoted by Pfizer by inhibiting the binding of substance P within the actual emetic centre, Mropotin provides a good broad broad spectrum effectiveness against both neural and humeral causes of vomiting, so those from the visceral areas and also the brain. Now things to consider with phlebotomy and chemotherapy, so was through these, but because they're just mainly handy hints and tips.

So, checking the patient's previous history, so how was it given, how was the animal position, for example, always considered numb. Treatments because this will be much more helpful in order to get better compliance for the patient, always assess their behaviour, make sure they're comfortable, and consider how long treatment is likely to take. So with doxorubicin example, that's about 20 minutes.

It takes a considerable amount of time. We use sometimes additional resources like beddings, treats and toys as well. And there's always a query about whether to alternate the legs, but what you must do is always document the leg and examine from the last treatment as well.

Catheter choice here. I've just put a quick slide in to show you that, there are different types to be used. I don't prefer, unfortunately, these, rigid needles because obviously they sit quite harshly within the vein.

Have a look at these types. They're fantastic. They're really, really sharp.

They're specifically made for animals. And so the animals respond much, like less of like jumppily with them as well. And they go in nice and smoother.

And then consider all the different vessels that you can use as well. So, the cephalic vein, especially the cephalic branch that we've got down here, the accessory veins, and this one that branches off on the, around the medial aspect of the leg tends to be really good areas to use. Also, the lateralinous vein and the medial subvenous veins are good points in which to administer chemotherapy safely.

You can get the animals laying down and nice and comfortable. And just some alternatives here, obviously animals where you can use the acular vein in the ear, and then the metatarsal arteries as well. They're actually rather large, as they branch down the legs as well.

Always approach your in your IV in a much more sort of like flatter plane. So none of the 45 degree angle, try to go a little bit more sort of like landing strips, so 30 degrees, maybe closer, because you don't want to be puncture in the vein or puncture in the back of the vein and leaking around it because you want those first catheters. And also consider your caregivers as well.

So get everything prepared in advance. Consider the comfort and the ergonomics, and do you need any additional help restraints, for example, and have some extra, have an extravasation or spill kit available. And always ask before you go ahead to give your chemotherapy, do a final check and ask if it's safe to proceed.

We get everything ready and it looks like this. And here's just a quick example of what we do when we give, our chemotherapy. So there are lots and lots of resources out there available, in order and how to safely give chemotherapy.

I've just really gone through today about the hints and tips, really, you know, you can always pause your webinar and go through this in much more detail. So, and, so as I say, there's a lot more resources out there to do so. Essentially summarised here, you do your IV checks, any dilution of the drug as needed, working over an absorbent pad where in your PPE before you then infuse the chemotherapy, flush the chemotherapy through all your, extension sets or your Y sets, flush then the syringe to make sure everything is clean and clear away from any residual drugs, remove your IV and then waste and identify it as well.

And I've just put here as well a summary of what we do for the infusion process for doxorubicin as well. Not all of us will, adopt giving doxorubicin in practise, so I won't spend too much time on this, but again, you are very welcome to pause and read through it. Just to note on oral chemotherapy as well.

So, oral chemotherapy is not dispensed in a liquid format or oral form, oral formation for administration. It's actually available as tablets or capsules and most chemotherapy is contained within an inert barrier coating. So as long as night trial gloves are worn, they're not, they shouldn't pose any risk to handling.

But it is, a couple of things here. I'm not gonna tell you how to give, like oral medications. I'm sure you're quite very well aware.

I've got some tips on the next slide, but don't ever brush, break or crush the tablets. Never open the capsules, and never, sorry, make sure all of the doses, are actually, available as a pre-formed tablet or capsule. So we shouldn't be prescribing half a cycloprostamide, for example.

Because the reason for that is for smaller doses of the chemotherapy drug, there are specialised compounding pharmacies that are available to reformulate cytotoxic drugs into much smaller doses, and oncology specialists, are able to help with that as well. So when you are given oral chemotherapy to make sure you wear night trial gloves, protective clothing, coating on the tablet could still break down once in contact with saliva. So the tablets or capsules need to be administered whole in a small amount of tasty food.

And to do so, it's great to just basically really get your animal excited. You want to be able to get them to chomp it really quickly without even thinking about it. So tease and tantalise them, make sure they're really excited.

And if that doesn't work, unfortunately, they need to be peeled directly into their mouth. I didn't have a picture of obviously somebody wearing gloves in order to give cytotoxic drugs, which we would be here. The alternative is to, use one of these pill poppers.

We find them really useful as well, so that they're put directly into the patient's, mouth down the back of their throat. And after you've, administered the drug, obviously remove any of your PPE and discard it into cyto toxic waste and wash your hands. This is also handy hints in which to give to your owners.

So dispensing oral chemotherapy for clients, you must make sure that these drugs are correctly labelled with dosing instructions, dispense in a childproof container with no cardboard packets, trim your blister packs into singles. So if you've got a blister pack of chemotherapy, chop them into singles and put them in your childproof container and make sure you put hazardous stickers on them to wear gloves and a cytotoxic. And your advice to owners should include to keep the chemotherapy or drugs inside the childproof container in a high cupboard away from them.

Keep the drugs in a dry and cool place and only give under the veterinarians instructions. Do not crush or break them, hide in yummy food, pill pop, or consider the application device. Wear, wear a pair of nitro gloves or if they're not available for some reason, double glove or using a latex examination glove with a rubber glove.

And obviously avoiding any children, pregnant women or immunosuppressive people to administer the drugs to animals. Now, what are we doing every single time so these animals are coming in regularly, they're having their chemotherapy. We need to restage them to see whether or not the, the, there's certain points within the treatment cycle if this is actually working.

So with our lymphoma cases, if you have a lymphoma, which is say in the bladder, for example, these animals get, you can't assess that necessarily very easy each time they come in for their appointment, as opposed to a multicentric canine lymphoma, which you can feel their lymph nodes. So what we're doing each time, when we're doing what's known as re-staging is we're remeasuring the size of that tumour, and that is usually done through imaging in order to measure what they had last time as a comparison. What does that information tell us like what I said before, we were looking to see whether or not they've got complete remission, progress, partial remission, stable disease or progressive disease, and it helps the veterinarian decide on what to do each next step.

So do we continue what we're doing? Do we transition something or do we need to change it? Oops, sorry, wrong way.

And then so we've talked about, the, a little bit about the myelosuppression. So what can happen to animals that have had chemotherapy, and I just want to run through an extravasation injury, and GI toxicity. There are a lot of other adverse events that could be associated with chemotherapy, which I've listed here, but we don't have time to go through them all in particular.

But it is worth noting that certain Drugs do certain damage to particular organs. We mentioned about Lomaine, have a negative effect on the liver. But doxorubicin, which is commonly used in the CO protocols, does have an accumulative cardiotoxic effect.

That tends to be after 6 doses or more, but it can actually, happen from the first dose. So again, it's something to be mindful of. So extravasation injury and cytotoxic, sorry, and chemotherapy induced nausea and vomiting.

So extravasation tends to be the most common fear for any administrator for chemotherapeutics. And this is because they are vesicant drugs which cause tissue destruction if they are extravasated. You could have really nasty blistering, necrosis and result in a long term injury.

And this is caused because the leak of the harmful drug outside of the vein, and it's very drug dependent, depending on the liver, different and causes different levels of tissue damage and different approaches to treatment. There's a great resource out there again, the American Animal Hospital Association guide to extravasation injuries, where a lot of this information and the next slide is going to come from. So the reference is there if you want it.

. The immediate action for all extravasation injuries is to stop the infusion. Don't take the catheter out, but try to attempt as much of the drug as possible and elevate the limb. And the first thing to do is to apply hot or cold compress, depending on what needs to be done with that drug.

So if you have, if you're proactive enough to get yourself an extravasation kit, then you can put all of the instructions and everything that you need within them in order to be able to progress to the next steps. But the bare minimums are described here before, your, obviously your clinician. Be involved to administer medications like we've listed here.

So the cortical steroids, hydrocortisone cream, things like that. But we do recommend you draw a line around the area to detect any progressive redness or development of the injury. Now there's difference.

So the idea is, is that with an extravasation injury, the with the cristine, you want to apply heat because you want to vasodilate it and increase the distribution and increase the absorption of the drug and therefore that in itself decreases local concentration, so it spreads and dilutes it. The opposite is needed for doxorubicin, where you have to apply cold, which causes vaso constriction. So therefore, the drug doesn't spread out and therefore reduces the distribution, allowing a reduced metapolic demand in the area.

And so the local blood vessels are therefore able to deal with it and disperse it. So this is known as localised and neutralised. With extravasation have been Christine, I've listed out here.

And so essentially what you there you prior your warm compress, you inject saline into the area, and then you massage gently to facilitate the dispersion. And there is a rescue remedy which is hyaluroninase. I can never say that, so don't laugh at me.

And you've got the A AAHA there, as reference in order to what to do. Same with Doxorubicin as well. And again, I won't lean too much on this, but those of you who do use doxorubicin, I strongly recommend that you keep in stock the antidote, which is Dexoraxone.

And if you can't get hold of Dexoraxone, and your practise is wanting to commit to use in Doctor Ruin in these protocols. I would reach out to other local practises or specialist centres to make sure they do have it and do stock it. So in the very rare occurrence that you have an extrasation injury, you have a plan of what to do with that animal if something goes wrong.

So, moral of the story is, is make yourself an extraization kit, which includes all of your instructions. We have these hot and cold thermal packs, you know, the ones which you crack and you can use. And so therefore, you've got those ready to go.

An additional set of PPE, which is then checked regularly, and we put a security seal on ours because you know what people are like when they're rummaging trying to find something. And then when you need it, it's not there. Listed out here is a few handy bits in which you can use in order to put together your emergency chemo kit as well.

So imagine adverse event, so gastrointestinal toxicity actually tends to have the strongest impact on the quality of life, and this is because, clients will discontinue treatment if these animals get really, really sick. And so the best plan is prevention. We mentioned before about premedicating our animals before they have their chemotherapy.

So if it's an emitted drug, prophylaxis is the best thing. And then the management at home through communication. So we often send animals home with a first aid kit for adverse effects.

So they're prescribed, Mirroitin and also ondansetron. So they continue them. Neopperton and they've got there and done to trying as a rescue and I'll explain in a second why, and we communicate with them and review things periodically because although adverse events are a common link to giving chemotherapy drugs, it shouldn't be normal and it shouldn't be acceptable.

There should be things that are put in place in order to try and reduce these effects. So we use ondansetron because it has an effect on the 5 HT3 reception receptors, which are actually, as you can see on our brain image that we saw earlier, the 5 HT receptors are actually in all three component parts that stimulate the, the vomiting response. And so, even that, so we have to follow that cascade, and so therefore we can then, if the moppotin doesn't work, then we go to the Onansetron.

The oral dose is 0.5 mg to 1 mg per kg, given every 12 to 24 hours. If they are nauseous post chemotherapy or, to pre-medicate them before, they get 0.5 mg per kg IV.

And then you've got diarrhoea as well, which is another adverse event that, sometimes, sometimes it occurs with the administration of some of these drugs. So chemotherapy, destroys the amplifying cells which live in the, crypts of the intestinal lumen. So essentially these grow and they come up here and they come up here and they come up here and then they die off and fall off.

So there we go, off they go. And then what happens is that it's thought that the, these cells take about approximately 6 days, 3 to 6 days before they sort of get up to this point. Now, because diarrhoea develops in these chemotherapy patients about 3 to 5 days post administration, it's Because it's thought that these amplifying cells are actually damaged as when the chemotherapy is given, similar to the neutrophils.

And so therefore, there is a break in these, so they die off, and then there's a lack of ability to absorb water. So there's a thinner layer, essentially. And then this cause also these goblet cells here to, respond to the inflammation of these cells dying, to increase the mucus.

So therefore you get, colitis with these cases, so they get a watery colitis-like diarrhoea. What do we do to manage these adverse effects? So they get, any mild symptoms, animals have just dietary support.

The treatment of these moderate to severe symptoms, they would then have metronidazole prescribed at 10 mg per kg twice a day for 5 days. And then to consider antispasmotics as well if they really are. Well.

But always bear in mind that there could be other reasons for this. So diet change, animals may, still, even though they're having chemotherapy, they, might, have parasites or bacterial infections or pancreatitis as well. It's amazing what these owners feed these, these animals once they've got a diagnosis of cancer.

But be always be aware that the impact on future treatments could be cause a dose decrease or discontinuing that specific drug. Now the best thing to do, I feel, is to make sure that we're proactive with our advice to owners. So the goal of, we have two leaflets that we give our clients.

So, first things first is the goal of chemotherapy and pets. So what are we doing? How does it work?

How is the treatment given? How long will my pet need treatment, and what, basic risks are they exposed to. And included with that, we list out the adverse effects and that these should be, infrequent and shortly lived.

We also give to our clients as well the safe handling of cytotoxic medications at home, which also talks about, if these drugs can harm anybody, how they can look to protect themselves, their family, the environment, how to dispose of waste and how long they need to, observe these measurements for. So rounding up towards the end of our lecture, our webinar now, it's just a roundup of what happens with the journey with these patients because unfortunately, they have a predicted response to treatment. If our survival time is the top arrow across the top, what happens here is our animals, when they get their first induction of treatment, they do go into remission.

So that's where we said we stopped the treatment and then we observe them, and then they relapse. So we start off with a rescue treatment, and then it's, that pushes them back into remission. Then we stop the treatment and then they relapse again.

Now this cycle continues and as you can notice the remission gets shorter and shorter and shorter, which and then unfortunately, they relapse and then despite another rescue treatment, they don't come out of their relapse and treatment failure is due to chemo resistance, drug toxicity, or reduced quality of life. Now the rescue treatments that are used, as we said, are either a reintroduction of original protocols, or we can replace one drug with another from a similar class, so change it up slightly, but not hugely, using Vlastin, for example, instead of incristine. We can change to the next efficacy, protocol or put in a completely new drug altogether or a completely new protocol.

But unfortunately, they do tend to come with more side effects and less efficacy, and we need to be thinking right at the beginning that the aims for these patients is a potential, we want to improve their quality of life through reduction of clinical signs. And if these come with more side effects and less efficacy, there is a potential for a reduced quality of life. So our lymphoma journey, these animals are presented to us unwell, and they might get, they have a diagnosis, given treatment options, they'll be restaged, rescued, and then unfortunately they enter a period of palliative care before euthanasia.

And throughout all of this, there is a huge amount of client support needed. So for us as nurses, introducing oncology nurse into your clinics involves many different aspects from the nurse consults, and deer and OS checks, chemotherapy, monitoring advice, adverse event support, pain assessment, quality of life assessment and bereavement, and there are many, many resources out there in which to develop yourself through all of these different aspects. The last bit here I've got here is the new treatment for canine lymphoma, because these things are really developing.

We said here that the gold standard treatment for canine lymphoma is chopped. That's got, that's the Madison Wisconsin protocol that gives us the best opportunity for these animals to get, to have a positive response for the longest time. But it's a long and then it's intense treatment with weekly treatment and monitoring.

So there's this new amazing drug out there called Tanovia, which is raphosamideathozidine, which is given every 3 weeks by 30-minute infusion for 5 doses and is provided through veterinary specialist centres. It does need a special treatment certificate, through the veterinary medicinesdictorate. And it's patented and it's promoted out there for a 77% overall response rate.

So given a a complete response to half of the patients that are treated with it. As I said, it's only available in veterinary specialists at this time, but it is something which is, out there for, patients which want to have a reduced visits, so to speak. This new drug does still come with complications including neutropenia, so myosuppression, GAI toxicity and extravasation risks.

So all of what we've mentioned with what we've had already. But also there are documentation, documented cases of pruritis, otitis, alopecia, and skin lesions, and some animals do develop pulmonary fibrosis as well. This progressive research, however, like, obviously this is a a marketed product.

There has been some new case presentations come out there and there's a research paper demonstrating that Alternate alternating doxorubicin and ra rapozidine every 3 week. So given three doses each, the overall response rate was 84%, which is not as good as COP because Cho, the the overall response rate is anything around in the 90s. So COP is still better, but less but more intense.

But it's still only has a similar response to just giving doxorubicin. Every 3 weeks or the less intense cop protocol. So it is a different thing out there.

It is available, but it's just something to show that, these things are progressing. There's some notes here for some further reading for those of you who like to read scientific papers and reviews. And we are there.

So thank you very much for the webinar vet for giving me this opportunity, and I'm sorry that we don't have time for questions this evening, but feel free to email me. My email address is at the bottom. Thank you everybody for listening.

Thank you very much, Nicola. Absolutely brilliant webinar and thank you for fitting in so much into such a short time. So as Nicola says, we don't have time for questions this evening, but she's kindly written her email address on this page, which is N Read at RVC.ac.uk.

So if you do have any questions, pop them through, and you can also ask any questions even if you are listening to a recording on the website at a later date. So on that note, I'd just like to say a massive thank you to our listeners and thank you so much, Nicola for taking time out of your evening to deliver such a wonderful webinar. Thank you very much.

You're welcome. Bye-bye. Bye bye.

Description

Transcription

Reviews