Good evening everybody and welcome to tonight's webinar. My name is Bruce Stevenson and I have the honour and pleasure of chairing tonight's webinar. Before we get started, just a little bit of housekeeping.
If you, want to ask a question of our speaker, please just move your mouse over the screen. You'll see there's a little Q&A box there, just click on it and, type the question in there and . Time permitting at the end, we will get through to those.
Our speaker tonight is, Nicola, and she is the head oncology nurse at the Clinical Sciences and Services Department at the Queen Mother Hospital for Small Animals. She's responsible for supporting the oncology services team of nurses, clinicians, residents, and students, as well as a team of patient care assistants who collaboratively assist with the care delivery in the medicine, cat ward, and emergency departments. Nicola's interest in oncology nursing resulted in her pursuing this unique specialised subject.
Studying a PGC in veterinary oncology nursing, and then more recently gaining an MSC in veterinary nursing. Her research project on subjective and objective methods of nausea, gained her an overall merit on her master's degree. Today, Nicola works closely with the oncology team to deliver individualised medical treatment to patients diagnosed with oncology disease and supports families through their treatment journey.
She has a keen interest in improving access to patients with cancer through education and research. Nicola, welcome to the webinar vet, and it's over to you. Thank you Bruce for that amazing intro.
So, welcome everybody. We're gonna talk today about what options might we have if our patient is diagnosed with cancer. So why is this topic so relevant to our practise?
Well, in dogs, the companion species where most data is available, studies have suggested that as much as 40 to 50% of individuals over the age of 10 die from cancer-related disease. So I'm sure with figures that high, you would agree that cancer is a major cause of morbidity and mortality in companion animals. The exact reason is unknown, however, similar to humans and with the advances of human medicine, pets live much longer than they did years ago and so cancer has become one of the most common causes of death.
In addition, the human animal bond that our ant companions hold for us is resulting in clients having high hopes for treatments of many diseases, and this too includes cancer. Many families have pets, more now, obviously since lockdown, as we've seen, and these animals are treated as part of the family. Whether so to provide a sense of security or companionship, motivation, stability or support.
And so we all acknowledge that pets hold huge value for many people, and these people, our clients, often want to do everything for that companion. For this reason, naturally, veterinary medicine has become to accept that cancer is a chronic disease and much researchers dedicate their time to developing innovative treatments or investigating of human treatments would also be a clinical benefit to animal cancers. So today in this webinar, the topic points that we're gonna go through within this 60 minutes, and I will be talking a little bit quick cos there's a lot to go through, is understanding the disease.
So we're gonna touch on different tumour types, how they're diagnosed, and a bit about staging, because all that's important to know what the enemy is. Then we're gonna talk about traditional cancer treatments, so, mainly surgery, chemotherapy and medic sorry radiotherapy. So their uses and any adverse effects, and so the availability of those to us.
And then we're gonna talk in the end about emerging treatments for cancer, so new and innovative things which are becoming more common in the UK. So we do have some learning objectives which I hope we're gonna achieve as we go through this session today. So I hope that everyone's gonna be able to identify the process to determine cancer type and the extent of disease.
I'd like you to be able to afterwards to list the traditional cancer treatments available to animals with cancer in the UK and understand which modalities can treat which tumour types. And then from doing so after the end of the session, hopefully you'll be able to evaluate the contents that we've talked about and determine where your learning will take you next. So tumour types.
Did you know that there are more than 100 different types of tumours, some with subclassifications? Most cancers are often named from the organ or cell type in which they originate. So I'll give you an example.
Cancer that arises from melanocytes of the skin is called a melanoma, or a carcinoma that might rise from the kidney is a is a renal carcinoma. Neoplasia is then grouped mainly into one of 5 different types. So you have carcinomas, so cancer that begins in the skin or tissues that line or cover internal organs.
And there are a number of subtypes, including adenocarcinoma, basal cell carcinomas, squamous cell carcinomas, transitional cell carcinomas, and their route of spread is usually through the lymphatic system. Then you have sarcomas, so they're cancer that begins in the connective or supportive tissue such as bone, cartilage, fat, muscle, blood vessels. And this route of spread, this type of tumor's route of spread is usually via the hematogeneous route or the bloodstream.
Then you have brain and spinal cord tumour cancer, sorry, and these are known as central nervous system cancers. And often the location of the tumour is the malignant component as it invades or crushes the normal functioning tissue that leads to severe clinical signs and subsequent morbidities. Then we have leukaemia, so cancer that starts and arises in the blood forming tissue, such as the bone marrow and therefore causes large numbers of abnormal blood cells to be produced and then go off into the bloodstream.
Often without the capabilities of these normal cells to fulfil their normal function. And so the patients then lack different, they end up with different problems, so they have coa coagulopathies, they lack immune protection, and they might have a limited oxygen carrying capiddity as well. And then there's finally lymphomas and myeloma, so cancers that begin in the cells of the immune system.
This can often be in a targeted localised area or disseminated or systemic. The way I think about these cancers when it comes to treatment is that some are systemic diseases. So in the case of the blood, bone marrow or lymphatic system, so your leukemias and lymphomas, that require a systemic treatment.
And then the other types of cancer I think of as targeted diseases. So for example, the neoplasia has originated from one area and that is where treatment is targeted. So for example the sarcomas and the carcinomas.
What's important to know that no two cancers are the same, nor do they behave similarly. And so it's important to know the tumour type and the extent of the disease before treatment options can be considered. So once the possibility of a neoplastic process is suspected, determination of the tumour type serves as the basis for all subsequent steps in the patient's management.
This is because all neoplasms act in different ways, and so a small solitary bump may look harmless, but it may be the tip of the iceberg when it comes to that animal's condition. And so jumping in with hundreds of pounds' worth of surgery may not be the best option in every case. What is instead recommended is that a biopsy is taken in the first instance to know what the mass is.
Now a biopsy is the basic tool that allows removal and examination of cells from the body to determine the presence, cause, and potentially extent of a disease process. Samples for analysis can be obtained by performing fine needle aspirate sampling for cytological examination or by various tissue biopsy techniques for histopathology interpretation. Cytology provides information based on the microscopic experience of individual cells.
Fine needle sampling can usually be performed safely for the majority of external tumours without sedation or anaesthesia, which holds huge benefit for cost and for the patient. Internal tumours, however, can also be sampled but needing usually ultrasound guidance depending on the location, the and the appearance and the size. And this, in these cases, sedation is usually necessary.
Subsequent submission of cytological samples to a clinical pathologist for diagnostic interpretation can often provide a definitive diagnosis of round cell tumours and can be helpful in categorising other tumours such as mesenchymal or epithelial. Although highly useful in determining tumour type, cytology does not always provide information on the tumour grade, which is needed to evaluate the biological behaviour of the tumour, which essentially means how aggressive it is. Unfortunately, cytological examination may not always yield a diagnosis.
So for example, if the cells that were submitted were damaged or it's not a representative sample of the mass, or if the tumour wasn't one that proliferates very easily to sampling. And so results may not be conclusive. Then we look at histopathology, whose goal is to provide a definitive diagnosis when obtainable by cytology.
Histopathology provides information on tissue structure, architectural relationships and tumour grade. The results, as I said of that are not possible with cytology. However, this technique often requires either deep sedation or anaesthesia, which undoubtedly increases the risk and cost to the clients, plus takes longer to process in the laboratory.
However, the histological tumour grade may guide the choice of treatment further and provide diagnostic information. And so there are both pros and cons to taking a tissue biopsy. When making decisions regarding cancer care, diagnostic staging is a mainstay of oncology case management.
Diagnostic staging assesses the cancer burden or extent of disease, and it's essential before embarking on treatment, as it could be questionable to put an animal through aggressive surgery, which may then require intensive rehabilitation if that animal already has metastatic disease with only a few months left to live. So staging is the process by determining the extent of local disease and the presence or absence of regional or distal metastasis using laboratory and imaging modalities. A thorough evaluation of the patient begins with a comprehensive physical exam and a minimum database.
This includes blood count, chemistry panel, and urinalysis. The scope of diagnostic workup for staging purposes is therefore then dependent upon the known behaviour of the individual tumour type combined with the owner's goals, limitations and expectations for therapy. So that's why it's so important to have had our biopsy in the first place.
Evaluation of the primary tumour then starts with the physical exam to determine the size, appearance, and mobility. See whether or not the mass is fixed to adjacent tissues. Then follows the regional tumour assessment, which involves evaluation of associated lymph nodes.
Documentation of metastasis to lymph nodes cannot reliably made by palpitation for size, and so other physical parameters and requires cytology or histopathology of the sentinel lymph node, submitted to a pathologist to assess the presence of infiltrative disease. Because lymph lymph node drainage can be highly variable, sampling of multiple nodes may be necessary for adequate staging. If a lymph node aspiray is not diagnostic, the lymph node cannot be assessed for whether or not it has got metastatic disease.
Internal lymph nodes, imaging is needed to assess and potentially guide the aspiration, and that may also be recommended. Imaging techniques are useful in the detection of abnormal lymph nodes, and they may include thoracic radiographs, CT and abdominal ultrasound. Distant metastasis refers to the spread of cancer beyond that regional lymph node to distant organs.
And so the presence of confirmed metastasis generally implies a worse prognosis and may then drastically affect therapeutic decisions. Therefore, complete staging is usually recommended, but can vary depending on the particular tumour type. Assessment for distant metastasis for highly metastatic tumours can usually be identified using abdominal and revi thoracic radiographs, abdominal ultrasound or sentinel lymph node mapping, nuclear centigraphy, bone scan, CT or positive emission tomography, so PET scan.
CT or MRI. What's kind of cool that we've got spinning in the video here is a 3D reconstruction CT image of a cat with an oral squamous cell carcinoma. That's literally on the front right hand side of its jaw.
The oncologist wanted to check which of the regional lymph regional lymph nodes of the mass was draining to in order to then target sampling for metastatic disease. As a surgery required be quite extensive and require a mandulectomy and would involve considerable cost and commitment. By using this sentinel lymph node mapping, it is becoming a common technique which is used in human oncology already and it is gradually being adopted in veterinary oncology.
It involves peri tumour injection of a contrast from the CT scan and then it has huge value for this surgical planning. So by now, we would have known what type of cancer we've got this animal has, and we would have done the staging in order to be able to determine how what kind of disease burden they've got. This is then when we can look at the traditional cancer treatment options.
The 3 mainstay cancer treatments for veterinary oncology patients are surgery, radiation, or chemotherapy. And so when setting the aim of treatment to control the cancer, the main basis of whether the care team are aiming for curative or palliative intent would be based on the evidence and treatments available for that particular cancer. Only if the veterinarian evaluates the patient to be well enough to have major treatment, the client will be offered a curative intent treatment protocol, which is only suitable for a limited number of cancers, which are usually low grade cancers, solitary lesions, and those that have low metastatic rates.
Or that those can be treated without significant morbidity to the animals. For many of our clients, this means having surgery followed up by chemotherapy or radiation after recovery from the operation. So studies examining different types of combination treatment have found that for most animals, this gives the best chance of getting rid of the cancer in the long term.
However, even with this treatment, the cancer can can come back always at a later time. And unfortunately, most often this happens within the 1st 18 months after the initial treatment. This is why we describe this type of treatment as curative intent.
We hope to get rid of the cancer forever, but unfortunately we know that it can come back even though with the best available treatments. The other treatment aim is palliative intent, where the mainstay of treatment sets out to decrease tumour load, alleviate clinical signs, and increase quality and thereafter quantity of life, essentially finding the best er modalities for the patient and their families to be able to live with cancer. Again, this might be used in just one of these 3 treatments or a combination of all of them.
We do know that due to cancer type and tumour load, that it's unlikely that the animal's cancer can't always be fully treated. Then the treatment offered is focused on reducing the clinical symptoms and helping the animal have the best quality of life. As we're focusing on quality of life rather than cure, we use the the phrase palliative treatment, which is a human oncology term.
And for me, to be honest, I don't think, I think this term isn't used enough to describe chemotherapy in animals. And I feel we would have a far better management of expectations if we did use this this terminology as it applies to most cancer treatments in animals. Curative intent is often not possible for the reasons we've already said.
In order to differentiate palliative treatment from palliative care, I think of palliative treatment as an action against the cancer. We're essentially still trying to treat it and stimulate a response, whereas the medical term palliative care is a drug or treatment or combination that relieves suffering without treating the case of the suffering, so the cause of the suffering. I hope that makes sense.
The reason why I'm highlighting this is because cancer treatments don't differ to palliative or end of life care. We mustn't forget that animals still have an end to their suffering by humane euthanasia as an option. So going into the first of our options, so surgery.
There's a diagnostic intent, which is to gather tissue for diagnosis. You can have curative intent. To remove all cancerous tissue with wide margins and so there's no cancer left behind.
You may do, there may be surgery as an option to cytoreductive . So reduce the tumour burden, so that's a planned incomplete excision of a tumour and is indicated when some er complete excision carries unacceptable consequences. Or there's palliative care surgery, so the purpose of the surgery is to improve the quality of that patient's life.
So a surgical biopsy is required when the fine needle aspirate is undiagnostic, which we covered a couple of sizes ago. And that incisional biopsy could include a needle core, a punch, or a wedge biopsy. And it's imperative control that the risk of the where you take that sample is very focused in order to reduce the risk of any tumour receding, .
They contained within the biopsy tracts, within where the future surgery is gonna be planned to ensure that the surgery can remove that area as well. You get my laser pointer pointer. There we go.
What I'm trying to say is essentially you can see here that the biopsy's been taken on the very edge of the mass so that it's much better there than a little bit further aside or if you've come from a more sort of like angled approach across here in which if some of the tumour cells can be seeded and therefore require a much larger margin. So excisional surgery, as a general rule, if a primary tumour can be completely side with acceptable morbidity, then surgery is the best choice of treatment. The first attempt at surgical excision always offers the best opportunity to completely remove the tumour.
Locally recurrent tumours often have more difficult to remove than the initial tumour because of more extensive involvement of normal tissues in the region, and therefore distortion of normal tissue planes by the scar tissue. For tumours that are large, fixed or located adjacent to critical normal structures, preoperative CT or MRI may be useful in helping to plan the surgical excision. The usual objective of surgery is to obtain wide surgical margins in all directions surrounding the tumour.
With a grossly visible intact cuff of surrounding normal tissue. There is, however, no universally appropriate margin width that covers all tumour types. Adequate margins vary from tumour to tumour and location to location.
Tumours with a high probability of local recurrence, for example, high grade soft tissue sarcomas or mast cell tumours and feline mammary carcinomas, should be removed with at least 2 to 3 centimetres margins if possible. However, many other malignancies can be safely removed with just 1 to 2 centimetre margins. The necessary margin often depends also in part on the type of tissues that are adjacent to the tumour.
So for example, fascial planes generally provide a good physical barrier to tumour growth. So that the excision of an intact flat fascial plane below a tumour is an excellent way to optimise the chance of a complete excision. Subcutaneous fat, however, is poorly resistant to tumour growth and is often infiltrated, and so should always be aggressively excised with the tumour mass.
A marginal excision refers to a shelling out of a tumour, and so it excises just outside of its sort of pseudo capsule, so what, what you can see with the naked eye. Because the pseudo capsule often consists of compressed cancer cells as well, marginal excision risks leaving microscopic quantities of tumour cells in the patient and so are associated with higher rates of local recurrence than with wide excisions. So as a general rule, marginal excisions should be avoided unless postoperative radiation therapy or subsequent aggressive surgery is going to be considered.
All excised tumours should then be submitted for histopathological examination and marginal analysis. And the report of incomplete margins unfortunately means that the resection was histologically incomplete in at least one location of the mass submitted. While overall recurrence rates are consistently greater for tumours with incomplete margins than for tumours with complete margins, owners should be aware, however, that tumours still, even with complete margins can recur locally and conversely, many tumours with incomplete margins may not recur at all.
Following a report of incomplete margins, options should include at the very minimum, close monitoring. And to see whether or not an appropriate re-excision would be feasible should local recurrence develop. Immediate wide excision of the surgical scar or postoperative radiation therapy should be also be considered if the incomplete margins have been reported.
You can see here on the images that I've got on the left, so this is a cat with a feline injection site, sarcoma, which is just above its scapula, which is here. And so these types of tumours are highly aggressive. You can see that it's gone through there, the fascial plane there, and then so they require very, very invasive surgery, often requiring a partial scapulectomy, the tips of the spinal processes as well taken, so that they make sure that they get a whole facial fascial plane down.
Down the bottom here we've got a patient which has got a scar, again with a feline injection site sarcoma. And then you can see, I hope you can appreciate here, you've got local recurrence along the scar tissue. Cytoreductive surgery is then also an option when the tumour is large or in a location where it is difficult for the whole tumour to be removed.
This may be, so we've got a patient here with a mast cell tumour on the front of its paw. You can appreciate that it's in a, in a place which is very difficult to surgically remove, so therefore, you could do some surgical cytoreductive surgery. This huge mass on the upper part of this patient's jaw, and then another mast cell tumour on this brachycephalic face.
And the whole idea is, is to remove as much of the tumour that can be seen with the naked eye, but what happens is, is that we have to accept that the microscopic deposits or tumour cells will still be left behind. The aim is never to produce a cure, but it will often provide long-term local control, prevent the mass from regrowing for as long as possible and hopefully delay the signs of any ill health due to the tumour. Cytoreductive surgery potentially increases the effectiveness of postoperative radiotherapy or chemotherapy because you're looking at a smaller, a smaller mass to target, as these two treatments are less effective when dealing with such a large mass.
Such a reductive surgery generally involves a minor procedure, so more of a minor procedure than surgery for a cure. So when we looked at the the patient before with the cat, we just scroll back, that's quite significant surgery. We've got drains in place, often they'll have a a wound soak catheter as well in order to deliver local anaesthetic.
So but these hopes for a much more minor procedure as opposed to those that we're looking for cure, so the recovery time after surgery is generally much shorter. And then I'm not going to go into too much about it, but palliative surgery is also an option as well. So for that dog which had the mast cell tumour on his paw, if the, if the dog hasn't got any metastatic disease, is young, fit, able, and not of an increased weight, then maybe palliative surgery to just remove the limb totally could improve the animal's quality of life and reduce the risk of any distal metastasis.
So that usually addresses the pain caused by the primary tumour. And a prime example which many of us think of is an osteosarcoma where an animal has a bone tumour that requires a limb amputation. Excuse me.
So then chemotherapy option 2. So chemotherapy is the use of drugs to destroy cancer cells. These chemotherapy drugs are called cytotoxic because they kill cells or they're cytostatic and they stop the cells from growing or dividing.
They have a a target effect, mainly on rapidly dividing cells. So cancer cells, which are hungry and they're growing, but they also affect any cell that's moving quite quickly through the cell cycle, and because this is where the chemotherapy drugs exert their greatest effect. Unfortunately, these drugs aren't always self specific, so they can affect normal cells, and that's why these animals suffer with potentially adverse effects.
Cytotoxic drugs have a high toxicity for normal cells with the high replication rates in animals that includes blood producing cells and the cells of the digestive system. Now conventional chemotherapy is otherwise known as maximum tolerated dose chemotherapy. And this is because the drugs have been established to have a clinical effect on on the cancer targets.
They, so we know that these drugs work for the reason that we're using them for. However, in animals we've determined a maximum dose of drug without moderate side side effects or what we call adverse effects. Now this is different in people because essentially you can sit a person down and you can explain to them and they make a a conscious choice in order to undertake the treatment that they're going to have.
And in doing so they could become extremely sick and they accept essentially what is potentially the risks for having this treatment because it may extend their quality or quantity of life. So we can't do that in animals and so there are published dose or protocols determined which have been found through clinical studies in order to find which is the maximum dose that a cohort of animals or a number of cohorts of animals can actually undergo in order to see a positive effect on their cancer, but not so much of a negative effect on their bone marrow, on their general health, their well-being. Their appetite, etc.
When with maximum tolerated dose chemotherapy doses are repeated at certain intervals, and this is because it requires the rest period between the doses for these healthy tissues to recover. So the tissues of the bone marrow and the tissues of the GI tract. The problem is, is that er cancer cell resistant leads to the treatment failure.
So over time along here, you'll get the animal will be getting their doses at set regular intervals. The reason why chemotherapy fails, is because we have a given dose of cytotoxic drugs, and it kills a proportion of cells. So this is our first treatment here, our normal cells across the top and the number of cancer cells.
So they're growing and growing and growing. They get their first treatment and so our number of cancer cells drops. And then there's a time between treatment 1 and treatment 2, where those cancer cells in the tumour burden increases again before they get another dose where more are killed off.
I hope that's clear. What has to happen is because the cells of the GI tract and the bone marrow also get killed off, and so we have to wait for those to recover back to normal levels in order to be able to safely give chemotherapy again. And that's an essential rest break in between, in order to allow the animal to recover.
So essentially this is why a number of doses are given of chemotherapy with the aim that the animal fully recovers in between. And that's where we have what's known as the dose, which is limited by the maximum tolerated dose. So it's only tolerated when the animal returns to normal.
So the indications for chemotherapy are mainly a systemic neoplasia or highly chemo sensitive tumour. It might be given for adjuvant chemotherapy or for microscopic disease or high risk of, metastasis. So when we were talking about the sarcomas and carcinomas, for example, which have high metastatic potential.
We may use it for neoadjuvant chemotherapy, so volume reduction to allow for local therapy. So where we mention for the cytoreductive surgery and the first option, chemotherapy might be used initially to try and target the initial mass to shrink it down in order to be able to get a better surgical margin or to get more of the tumour if possible. So I didn't explain, sorry, adjuvant chemotherapy is when it's given after the surgery.
So you give that subsequent to it, and then neoadjuvant is prior to. So it's not, chemotherapy is not indicated when there's a more effective option. So for surgery, for example, it's better to take the mass off if it's it's a type of tumour which is, better suited for surgery.
Whether or not some neoplasms are not sensitive to chemotherapy, so low grade tumours, so ones which are growing aggressive, but they're very slow to populate, because chemotherapy, as we said, targets rapidly dividing cells. So chemotherapy can be administered in a number of ways. It's normally an injectable agent which can be given er on the right here, this is via a plural port, so into a plural space.
They're all the injectable drugs or you can be so it can be given IV, in a pleural space, or they can be given orally. Obviously this is just a a internet image because if that was a chemotherapy drug we'd be a bit more careful. And then the chemotherapy protocols are given, so we saw in the last couple of slides that they're given at set routine intervals.
And then there's a combination of whether they're used as single agent therapies or multi-agent therapies. So single agent therapies in the majority of times are at lower cost and less toxicity, and that's because there's a, if you're using multiple agents, they're obviously gonna be at higher cost because there's more drugs involved. There's more, monitoring required for the patient in order to make sure that there's not having a cumulative effect of all the different drugs.
There's so there's less toxicity of a single agent usually, and but there's a higher risk of toxicity when you're using multiple medications. Single agents, they're very rarely hospitalised because the animal is being given a longer time to recover, versus if you use different agents, they're gonna have a different response every single time you're using a different agent on a different week. .
Unfortunately, single agent therapy though tends to be less effective, because essentially what happens is, is that the the drugs, the cancer becomes clever. It's like a virus, think of it like the COVID virus now with all the different variants we have. The cancer's very clever and it becomes resistant.
So if you're just showing them one drug from the beginning, what happens is, is there's a higher chance to chemo resistance will happen earlier. Whereas if you use multiple agents, yes, it's a higher cost, yes, there is a slightly higher risk of toxicity or and the animal getting sick. However, they tend to be more effective and have a prolonged effect and so chemotherapy resist chemo resistance is slower.
I'll just give you a couple of examples. So treatment for cancer, a systemic neoplasia, so the goals are to induce remission and alleviate clinical signs. For example, here we're gonna use canine multicentric lymphoma.
If we do nothing, the mean survival time is normally just 1 to 2 months. However, if we use an intensive protocol, which is the gold standard, which is the COC protocol, so a combination of cyclophosphamide, doxorubicin, bencristine, prednisolone protocol, these animals out of 100 of them, on average, will have a 90% response rate. So these animals will be pushed into remission, so they'll have their clinical signs alleviated, 90% of them.
Of those 90% of animals, 50% of those will survive for 12 months. And then of those that have survived 12 months, 20% of those might survive for 24 months. And even though it's quite a small statistic, still 5 in 1000 dogs will survive more than 2 years.
So it is, it is a case of giving these animals medications in order to prolong their life. However, if their clinical signs are alleviated and the animals are in remission, then they can have a proactive and prolonged life which has which is obviously has quality to it. Then adjuvant chemotherapy, so this is chemotherapy following surgery.
So the goals of that is to kill any micrometastatic disease and increase disease-free intervals. So our example here is a canine splenic hemangiosarcoma, which has a hugely high metastatic potential to the liver, the. The kidneys.
We said it in one of our first slides, so, sarcoma spread through the hematogenous routes, so through the bloodstream. So as the blood passes through anywhere, as it's passed through that tumour, it's picked up and micrometastasis can drop anywhere and create a new colony of tumour. So the options are, if we did nothing to this animal, they, with a hemangiosarcoma like that, they could end up literally, that could bleed and they could have just days to live.
Surgery, on the other hand, so took out the, their splenic hemangiosarcoma. They could live for another 2 to 3 months, but as we know that this, tumour has high metastatic potential, following it up with adjuvant chemotherapy afterwards can have a A survival time of 6 to 8 months. However, saying that, I have seen animals live much, much, much, much longer.
And so the mean survival time, which is always quoted in the papers that we read and we look to reference for, is an average, so that's an average of patients where there are extremes on both levels. And then neoadjuvant chemotherapy is an example here. So chemotherapy given prior to surgery, so to make non-operable tumours more treatable and preserve organ function.
So for example, feline injections like sarcoma, you can appreciate on this image here, this is a huge mass, absolutely huge, touching the spinous process here, and, at the level of the scapula or invading into it as you can imagine there. They have a very low metastatic potential, less than 25%. However, they're very aggressive local tumours and require, like we said before, extensive wide surgical margins and a high and have a high recurrence rate.
So the options are surgery, neoadjuvant chemotherapy. And so this is another opportunity where we can have a look at what we can do more with these animals. Unfortunately with chemotherapy, we have said that they in chemotherapy inhibits the bone marrow from producing the white cells or destroys the blood cells and the blood or bone marrow and causes a neutropenia, which is short or long term.
But in addition, chemotherapy does have other adverse events, so GI toxicity, hair loss, organ damage, extraization injury, urinary incontinence and behavioural problems, just to touch on those. Unfortunately, as I said before, that chemotherapy fails due to the chemo resistance. And so what it looks like on a sort of a graph, these animals go into remission and then they relapse because the cancer gets clever.
We try a different drug, and they go into remission, they relapse and these get shorter and shorter and shorter until there's no other options for them. Moving swiftly on to radiation, so radiation, produces, uses high energy electrons to destroy or damage cancer cells. Now there's two ways in which radiation is used, so it's either for, curative intent or palliative intent, and it's used in alone, again, in combination with cancer treatment.
So, pre or post-operative, surgery or pre or post chemotherapy. And it can be given in 3 ways, which are external beam radiation, internal radiation, or systemic radiation. Now, definitive intent radiation, the primary goal is to eradicate all tumour cells within the mass.
And the aim is long-term tumour control. So we're aiming for more than 6 months to years disease free. And it's administered to localised tumours, so usually brain tumours, nasal tumours, oral tumours, or tumours of the extremities like on the foot.
And the treatment period is around 3 to 4 weeks with small fractional doses, so repeated over and over doses of small doses of radiation, usually administered, say Monday to a Friday each week, and the animal goes home for the weekend. Now temporary side effects may occur, and they're usually resolved within 3 to 4 weeks after the course of radiation is completed. And then there's palliative intent radiation, which is indicated when the patient has advanced cancer, plus or minus metastatic disease.
And therefore, the main goal is to relieve pain and clinical signs in order to improve or maintain quality of life. There's the intention to shrink, shrink or stabilise the tumour, and most of these protocols use fewer fractions, but a much higher dose per fraction. And so a lower total dose is given compared to the definitive protocols.
Now palliative therapy rarely causes acute side effects, but they're associated with long-term side effects. But we don't see so many of these cos unfortunately, the palliative radiation is given to control the pain, and the animals don't live for a huge amount longer than that. Now, the side effects that we might see are the acute, so, towards the end of the treatment, and these are common, and they occur shortly, after treatment or during, and they have like this sunburn effect.
So they look really quite sore and blu blushed, and then you end up with this discrimation, and then any, radiations that's occurred around the face, they can have a mucoussitis, . They are palliated with systematic career symptomatic care, sorry, pain relief, and it's really important that they have, they're prevented to self traumatise. And as I said, the long term effects are very rare, but they can occur months to years after treatment, and this can include tissue fibrosis, subsequent tumours, or even a fracture to the area.
Now there is becoming more and more available is intensely modulated radiation therapy, which allows the beam to be tightly shaped to the tumour and allows the sparing of normal tissues. It involves using a collimator to move the beam around the animal during treatment, and so it has different angles and distances during a single treatment. You can appreciate here hopefully that by using IMR IMRT sorry, so this is a conventional method.
So it's targeting this nasal tumour here on the dog on the left and the nasal tumour here on the dog on the right, but it's its left nose. So it's much more targeted around here. So you can appreciate that this is this dog's lip down here, which is also In order to get the angle into and access all areas of the tumour, it's hit the lip as well, and potentially also the tongue.
Whereas by using IMRT, which is a much more modern form of radiation therapy, which is becoming much more available now, it's sparing much more of these tissues and the higher intensity beam is much more localised here, which you can see the difference in these two animals. Now there are a number of factors which may influence treatment options presented to the owner and so that might be whether or not to treat the animal at all. So we can look at the neoplasm, whether it's the tumour type, the location, the size, the predictive response, and behaviour.
This may narrow the treatment options in the first place. The patient's suitability, age, weight, morbidity, so an osteosarcoma, for example, in a large elderly mastiff may not, may limit the option of surgery. Behaviour.
So some animals that might require multiple visits, they might not be amenable or even stable enough to travel or be treated. Obviously cost is a major factor as well. Personal beliefs, some people may have religious belief, reliefs which they've developed as their own experiences.
As well, the frequencies of visits, the owners might find difficult to balance around home life and things like that as well, where they may live in a location where some of the treatments aren't available, and obviously the administration of these for some reasons of behaviour we've already mentioned that some caregivers may not be so forthcoming or comfortable in using such treatments and therefore not be able to administer them in general practise. And then so adjunctive therapies have long been used as a means of improving the quality of life in veterinary patients, and now they're accepted component of oncology case management. Because the quality of an animal's a person's pet is usually the first owner's concern, decisions on cancer treatment should not only consider disease factors but also the owner's goals, preferences and limitations.
A variety of adjective therapies are employed in controlling clinical signs encountered with dogs and cats, that being treated for their cancer yet can also be used as a form of palliation when the owner makes the decision not to treat the animal's primary disease. We've said this a few times now, but I think it's really important that, without spending too much time on this slide, that palliation of disease should always focus around recognition and the control of pain, the nutrition and the animal's hydration status, and always remembering the human-animal bond by having all different innov in interventional treatments, . Things like that.
The human anabolic bond is a significant factor to be mindful of when it comes to supporting patients and their families who've chosen palliative care, because the necessity to medicate these animals and address the symptoms of cancer can result in aversive behaviours like hiding or shying away. And then that can damage the relationship with its owner, which is possibly one of the most important reasons for the animals being. So lastly on to some oncology treatments that are emerging, which is quite exciting, I think.
So we'll go through those now as we're rounding up. Yeah, 15 minutes for these. So interventional radiography, so essentially it's a palliative measure to preserve function.
So there is a possibility that, stents can be placed in order to maintain, . Basically keeping a tube open, so to speak. Their main indication is usually with urethral neoplasia, so bladder, prostatic cancers, metastatic disease, things like that, and it's to prolong quality and their duration of life whilst preserving the function.
It's, they come in the form of a mesh stent that's deployed past the extremes of an affected area to light, to dilate that area. There are risks of side effects, unfortunately, like with any interventional treatment. So if we're looking at bladder tumours or uteteric tumours, there's the risk of persistent leakage, so to speak, because you're keeping that tube open all the time.
I've got video to show you in just a second, so if you can just visualise that this is the catheter that's gonna be placed into the patient and this is where the stent is, you're gonna see that in a video just now. So it's an animal with a prostatic tumour. Hopefully it will play for us, she says.
Oh, hold on, maybe it's just coming. Here we go. So try and click.
Yes, here we go. So essentially this is a video of a prostatic carcinoma being stented. So this is a contrast study.
The animal's urethra is up here, so it's exitin part, and they're just injecting a contrast study into the bladder. The animal's prostate is here where it's got a prostatic carcinoma. So this is a stent, so they're the markers on either side, and you can see the stent being deployed across here, so it's opening up.
So keeping this obstructed area here open. So all the way along, so that's the stent being deployed in order to keep the urethra open. And then they'll fly in the contrast, and now you can appreciate that this animal's less obstructed as what it was before, hopefully.
Oops. How do we go to the next one. Stop, maybe.
Hm, let's just do that. The end? Hm, I wouldn't it let me do that?
Oh dear. Sorry guys, it did work really well before. Let's just move on.
Is Bruce gonna come and help me? Nicola, if you move your cursor to a click mouse and then in the bottom left corner, you'll see that as you move your mouse, right down the left side of your screen, there they are. Fab.
Thank you, sorry guys. So moving on to electro chemotherapy, which is a cool new, thing that is available to veterinary patients. So it's the application of short and intense electrical pulses to transiently per permeably the tumor's, cell membranes.
So by applying a an electric current, almost makes the cell membrane temporarily. So open its doors, so therefore chemotherapy can enter the cell more freely and then when the electro chemotherapy is stopped, sorry, the electrical pulse is stopped, that chemotherapy stays within the cell. It causes enhanced level of cell death and it's actually suitable for a number of different epithelial or superficial tumours.
A study which was looked at nearly 2000 tumours in 2013, various different types and found that an 80, nearly 85% response rate, mainly to squamous cell carcinomas and equine equine sarcoids. Is limited to a small number of specialist centres, but it looks like this, so essentially these are the probes and they are placed superficially like the one on the left. Let me do my pointer again do do do do do.
Yeah, so the one on the left here is like a prong which sits on the surface, and then these ones literally go into the tumour and then that's where the electrical pulse is delivered. Looks like this, so patiently animals will require a brief general anaesthesia. So they have a surgical standard prep of the site, and then chemotherapy is injected either into the tumour or it's injected intravenously, so it's systemically in the patient, depending on health and safety and that evaluation.
They tend to do the injection into the tumour in. Places outside the UK, whereas in the UK we tend to be a little bit more conservative, so we'll give that IV. And then the pulse is delivered onto the onto the level of the tumour and then it goes in sort of a clock, like a twisty treatment area, so going from left to right, all the way across in this pinwheel approach.
It does a really, really good job, in many patients, so this is only after one ECT session, so A before treatment, B 2 weeks after treatment, so it's killing off these cancer cells which form a scab, and then 4 weeks post treatment, is image C here and then 8 weeks post treatment. So whereas normally we would be looking at surgery for these animals where they have quite severe surgery as well, this animal, this lovely cat has managed to keep his nose. So there's chemo embolization, which is a combination of local delivery of chemotherapy, and, this procedure is called embolization to treat the cancer, which is normally most often in the liver.
Chemotherapy is injected directly into the blood vessel, feeding a cancerous tumour, which is really cool. So I'm gonna show you a short video where they are gonna feed a a catheter in and deliver chemotherapy directly to that area. So let's see if we can make that work better, let's just load it up.
There we go. Let's play that. For patients with tumours in the liver, transarterial chemo embolization is a minimally invasive targeted treatment option.
During the procedure, the doctor inserts a thin catheter into a vessel in the groyne. Using X-ray imaging as a guide, the doctor moves the catheter to the specific vessel that supplies the tumour with blood. A mixture of chemotherapy and ymbolic particles.
So there's your chemotherapy being delivered directly into the tumour targeted treatment is delivered directly to the tumour. This prolongs the residents time of chemotherapy within the tumour, enhancing its effect. So all the chemotherapy has been delivered directly into the tumour and now 4 to 6 weeks later.
Because these chemotherapy Let me try to move that down here. The particles are applied. Oh, there we go.
So that's kind of cool. Essentially what that was you were seeing there is the the chemotherapy being delivered directly into the liver, and then those small beads essentially, which is chemotherapy, which has been embolized within like little beads, so it kind of like blocks off the capillaries and then er releases the chemotherapy very targeted. It's as far as I'm aware only being used in one centre towards the sort of like south of the UK but I'm sure other specialist centres will be using that too.
Just a quick bit about immunotherapy. So this is to use the body's own immune system to attack the tumour. There are numerous treatments available in human medicine, so immunotherapy is a big thing with human medicine, but there's only one marketed at the moment for use in animals, but there are others being developed.
In particular, everyone's getting very excited about a, osteosarcoma vaccine, which is, almost here. Immunotherapy is, limited to just oncology specialists, and the, the oral melanoma vaccine, which was licenced in the UK but not, sorry, in the USA but not in the UK, so it has to be brought in a special treatment licence, hence why it needs to be done at an oncology specialist. It's given by a transdermal injection every 2 weeks.
So you get the animals get 4 doses, and they have a booster every 6 months. Now this works by the tumour DNA proteins are essentially injected into the patient to harvest an immune response to foreign material. Very similar to say a vaccine in which a small dose of that cancer is injected into the animal.
It results in an immune system attacking the cancer cells with a similar protein. And so, there are very, very positive, reports out there to say that it works really, really well. There is questioning though, however, with some efficacy of it.
So, they, they, the trials which the company did were missing, randomised clinical trials, so not say gold standard, in which, an animal is, randomised into different groups. It does use a human DNA protein, not a canine, so we're not sure whether or not it, the animals are able to harness the same response as if it was a, an, a canine protein. And because it's more of an aggressive disease in dogs than it is in people, so it's been formulated very similar to a human model, it's more aggressive in dogs.
So does it, does the vaccine have long enough in order to work, because 15% of these animals die within the 1st 3 months of the initiation and treatment, so does it have enough time to work? They have looked to see whether or not it works in cats, and cats being such sensitive creatures, they do have more side effects. And again, most die due to disease progression.
And so there was another another, paper, sorry, that looked into it as well. And so, the idea is that maybe it's more of a palliative treatment for oral melanoma. Just want to round off the session just with some metronomic therapies.
So this is a treatment of using low dose or low doses of anti-cancer drugs, usually cyclophosamide or chloramacil, given on a continuous or frequent regular schedule. So it's just daily or weekly. Over a long time.
So we're given similar drugs that we would use in normal intensive protocols, but, more frequently, but less a much smaller dose. Therefore, the idea is that this spares the host cell, so causes less severe side effects than traditional chemotherapy. And treatment is often combined with CO2 inhibitors, and the aim is to stop the growth of the new blood vessels that the tumours need to grow.
The idea is, is that er we are aiming instead for stable disease or slow progressive disease. So learning to live with the cancer rather than fight it, so to speak. So, tumours require access to the vascular system, as we know, to gain nutrition and to grow.
And the vascular system is also a conduit for metastatic spread. So angiogenesis, so the growth of new vessels from existing vasculature, is a hallmark of cancer and a target for human and veterinary cancer treatment alike. So if we can prevent angiogenesis, so, prevent the growth of new vessels, then hopefully we can stop the spread and we can starve the cancer.
And there are chemical modules, molecules, sorry, associated with angiogenesis, which are the main focus. So the COX, and veg F. And so just to put this this in a diagram format, so vegF is a signal protein produced by cells that stimulates the formation of the blood vessels.
And then COX is an enzyme responsible for the formation of prostaglandins that are important in the contractility, so creating good blood vessels and the coagulation process. And then you've got the COX2 though, which is derived proxy glanders that promote the cell growth, proliferation and angiogenic expression of the tumour cells. And then regulatory cells are released to suppress tumour response that are found to be elevated in certain cancers.
So what's happening here is you've got cancer cells that are eliminate proliferating all of these chemical messages in order to create more blood vessels in order to feed the tumour to make it grow, and then also act as a pathway for metastasis. So if we can target angiogenesis, there are advantages to low dose metronomic chemotherapy instead. So these animals living with cancer, like I said.
So they are oral treatments, so can be administered at home. They require less frequent monitoring, they're lower cost, a low prevalence of side effects in the, in the main, and then these animals continue to maintain their quality of life. So low dose metronomic chemotherapy is being used much more.
And since described over 15 years ago, there's been well over 100 metronomic trials been published and adopted as recognised treatments for a wide range of tumour types, stages, and all ages, and this is in with people. And therefore it's gradually being looked at and researched and adopted into veterinary medicine. There's a couple of papers there which are good to read if you get a chance.
So, but there are some challenges, of course, because we are talking that we're using chemotherapy drugs anyway. They can be gastrointestinal toxicity. With cyclophosphamide, there is a risk of bladder toxicity.
There can be myotoxicity, so an impact on the bone marrow with chronic use. Some of the research that is out there is inconsistent, unfortunately. These might be used because owners have decided.
Not to give, traditional chemotherapy. And so it's like, oh, maybe we can try this instead. And so, therefore, some of the research is inconsistent or even conflicting.
And so controlled studies are needed. And there can be the risk of compliance from the clients who almost may be able to treat these like sweeties. And so we need to make sure that these animals are monitored in order to make sure that they don't have any of these adverse effects.
And then finally just move into TKIs because we are seeing more of them being used. So ter tyrosine kinase are enzymes found on the surface of the cell membrane, which are responsible for the activation of proteins involved in the signalling pathways that regulate normal. Cell proliferation and survival.
So we looked before how we're using COX-2 inhibitors, and chemotherapy, and now we're looking at veg F which is vascular endothelial growth factor, which is a signal protein produced by many cells stimulating the formation of these blood vessels. And bed Jeff has been found to be elevated in certain tumour types. Therefore, TKIs are anti-cancer drugs that block this signal transduction, ultimately preventing tumour growth or in some cases starving the tumour from being able to survive off of the host.
There are two oral TKIs approved for use in dogs with cancer, Tocceanib and mecitinib, which are indicated for the treatment of specific grades and stages of mast cell disease. Although these drugs are targeted to specific signal transduction pathways, each drug can induce toxicities to rapidly divide in normal cells as well that also rely on these pathways. The most common side effects seen with these are gastrointestinal toxicities including diarrhoea or loss of appetite and occasional vomiting.
And other less common side effects are hepatotoxicity, neutropenia, muscle pain, coagulopathies. Side effects associated with Taserinib also include protein losing PLE sorry, and protein urea, hypertension and rarely pancreatitis as well. But more importantly, more widespread use of TKIs does await their investigation of several important questions, such as tumour types in which TKAs are more likely to be effective and their optimal combination with conventional chemotherapy agents.
However, many specialists are using them off label for various tumour types with some very positive results. So that's all the new things that are out there, some in veterinary specialists, some in sort of your bigger general practitioners who are becoming much more er innovative with treating patients. So just to summarise what we've talked about today, so cancer treatment is very case specific and it's multifactorial.
Treatment modalities are based on the tumour type and its stage, and staging is a critical factor in deciding which treatment modalities to use or whether to treat the cancer at all or to instead rely on palliative measures. Chemotherapy, immunotherapy, adjunctive therapies, radiotherapy and surgery can all be used individually or in tandem depending on the type of cancer involved and the owner's preferences. Chemotherapy is now much more commonly used in oncology, however, there's inherent toxicity with some of these agents and strict safe precautions to avoid exposure of the patient, personnel, pet owner, and the environment also need to be taken into consideration.
The quality of life for the patient and indirectly for the owner is central to any cancer case management. Imagine the patient's quality of life includes maintaining a reasonable level of pain-free functional activity during treatment and minimalizing any side effects. At times, in particular in advanced cancer cases, maintained in the patient's quality of life and extending its lifespan are mutually exclusive.
The decision on how to achieve a balance between quality and quantity is complicated by the fact that cancer is often a disease of older pets. The time of life when the pet owner relationship is probably at its strongest. Because cancer cases making clear with the death of the euthanasia of the patient, making sure that everyone has what's, for want of a better word, to satisfy an outcome for everybody, is highly dependent on good communication between the care team and the client.
And this dialogue should include all members of the healthcare team that is collaboratively equipped to manage their owners' expectations and guide treatment decisions and provide emblematic client support. So for us as nurses, our support role is to play a large part in coordinating and implementing the care of these animals. Administering chemotherapy drugs is becoming much more common practise, whether it's for palliative treatment or whether or not it is for some of the newer drugs or metronomic therapy, and therefore advising these clients on how to use them and administering them safely.
And then provide care and information on rehabilitation for animals that have had surgery, or have had radiation and need to be back to mobilised, skin repaired, things like that. It's our responsibility to always document all patient and client interactions to make sure that there's, it's clear for the next person who's going to encounter that client so that care plans can be consistently delivered. And it's our responsibility to help measure and manage both the symptoms of a patient's disease and help the owners identify side effects of these various different treatments, and help be able to implement enhanced care plans.
So that was a big whistle stop tour of all the different types of treatments that there are available. I, you could go into a webinar for each and every one of them, but I hope that struck up some interest in everybody, and you can look at for more things online and other webinars in order to satisfy your interest. Yeah.
Nicola, that was absolutely fascinating. It really was. Thank you so much.
As you say, it's, it's, if nothing else, it's, it's given great insights and, and I'm sure stimulated a lot of interest, in the topic. So thank you very much. You're very welcome.
Thank you for listening. Just a word of apology to those of you that were affected by the technical difficulties in the beginning. I am aware that some of you may have missed up to 15 or 20 minutes in the beginning.
I do really apologise for that. We're not quite sure what went on, but we have got recordings and those recordings will be up in the next 24 to 36 hours. So, big apology to everybody if you did have, or were affected by those technical difficulties, but, it really is worthwhile going and, and watching this again, especially if you missed that first part.
There's a lot of great information in there. Nicola, I think you've done such a good job that we actually haven't had any questions coming through. So it is just my privilege to have been here tonight and to thank you for your time and the fantastic presentation.
I look forward to having you back on the webinar vet in the future. Thank you, thank you everybody for the opportunity to speak to you on the subject. I hope you've enjoyed the session.
My email address is there, so if there are any questions that pop up at a later date, feel free to email me. Thanks everyone for listening. Thanks everybody for attending and once again, sorry for the technical difficulties.
Catch the recording on the website and I will see you again on the next webinar. Thank you and good night.