Welcome to my webinar radiation therapy in Dogs and Cats. What do I need to know? My name is Juan Carlos.

I am a radiation oncologist at the University of Edinburgh, where a small animal oncology. I have been trained in both medical and radiation oncology, and the reason why I think this topic is relevant for general practitioners is because of the growing interest in, in The community of, of pet owners in treating their pets cancer with a gold standard way and the way they really support themselves on, on the trust and, and the help of a general practitioner to guide them in this difficult decision time. Therefore, I, I, I feel it's, it's quite relevant actually to, to know the basis of this modality as it offers so much, for, for pets with cancer.

So, to start, we're gonna just have a brief talk about the different potential options for oncology treatments. Mainly we can divide treatments as local or systemic and against what many people think, local treatment plays a much more major role compared to chemotherapy or other systemic treatments. The reason being that with systemic therapies, you have to limit your dose significant exposure of the whole body, whereas with local treatments you can, you can be much more aggressive.

Obviously, surgery is by far the most effective way of treating cancer both in humans and in pets. But radiation therapy also actually also plays a, a very important role. So around.

50% of humans will, with cancer will receive at some stage during the treatment, radiation therapy, and it is associated to a higher rate of cure radiation in comparison to chemotherapy or other modalities given systemically in humans. Radiation therapy is a very broad term. It basically just refers to using ionising radiation for treatment of a condition.

These most commonly will be cancer, but there are some benign conditions that we will discuss later that can also be treated with radiotherapy. And depending on how you administer this radiation, you can have different forms of radiotherapy, radiotherapy, brachytherapy, lasal therapy, or systemic radiotherapy, which I'm very you're going to describe just now just so you know that they're out there. So basically the first would be teleadiotherapy, teletherapy, which would be this machine here, this is a linear accelerator and teletherapy means there is a distance between the source which would be here, that's where the energy is going to come out, and the patient which will be lying in the table.

. There is a head, the head of the country is, is here and that's where the, in the, the radiation is going to come out from a hole that basically has a lot of little leaves that can create a shape so the bean shape for the area that we want to treat to basically spare the normal tissues and focus more. And this would be the most common way of treating cancer nowadays in, in. We also have the systemic therapy and this is basically limited to mostly limited to I I131 IG 131, which is a radioisotope that is basically Accumulated in the thyroid because it takes iodine and this type of radioisotope has a very limited branch of extension of its radioactivity.

So the, the damage is going to be caused locally at the thyroid gland where it is being accumulated. It most commonly used for hyperthyroidism in cats, and that, is actually offered in multiple practises in, in the UK, in in England and Scotland, but it can also potentially be used for, aggressive thyroid tumours in dogs and it can potentially control the tumour for, for, for some time. Then we have brachytherapy, which is definitely much more commonly used in humans.

Brachytherapy means you're placing a source that is radioactive inside patients, so either in a cavity or in the interstitial. In dogs and cats is very infrequently used. I don't think there's any place that uses it in the UK.

However, the, it is used in horses, especially it was used in animal health trust, for different type of humans in the, . Then we have laotherapy, which is a some type of brachytherapy form, and basically you're not putting the source inside the tumour, you're actually just Putting the sources in contact with the tumour. The, the, the good thing of this type of therapy is that it, it only acts very superficially, it can only go deep through a few millimetres.

So for skin lesions that are very superficial, you can give a very, very high dose without causing toxicity to the underlying issues. So it can be very effective against visual tumours in cats such as muscle tumours and . Carcinoma especially.

This probe was present in the animaltra as well and I think now it's gonna probably move to Cambridge, but it's not available that I know anywhere else in the United Kingdom, very, very effective and useful for some specific human types. So back to radiation, this is basically defined in two groups. You have non-ionizing radiation and ionising radiation.

The important is very, very significant. Non-ionizing radiation is that one that doesn't have enough energy to eject an outer electron from an atom, and this is going to make it safe for us. So for example, the radio waves or the microwaves from the mobile phones or from the airports, those are not going to be a hazard for us because they're not ionising.

Whereas ionising radiation is that one that has enough energy to actually get electrons from an atom, and they're going to be used for either diagnostics or for quick. There are many types of radiations and which one the radiation oncologist will choose will depend on first, how does the radiation oncologist want the distribution of the energy to be in the, in the patient. So for example, some of these variations will go very superficial, whereas others will go very deep.

But also in regards to the availability in veterinary medicine, the ones in red X-rays, gamma rays, and electrons are are commonly used in pets, but none of the others are and in part it is because of the cost associated. So for example, the new proton therapy machine in London for humans has costed more than 100 million pounds, which obviously wouldn't be feasible, from a point of view for for cats, although there are still some studies coming out, our research studies and really clinical studies. So how does therapy work?

We're saying that we're sending energy, high packets of energy that are going to be removing electrons from atoms. What's gonna happen then is that this election is gonna create a free radical and the free radical is going to damage the DNA. And typically the most common thing that happens is that that DNA that is broken will cause the cell to die when it is trying to divide.

If the cell is not dividing it's not so much of an issue, it's more when it buys in many cases. And therefore it does take a few days typically to, to cause the damage. It's not immediate.

Also the tumours are potentially going to be more sensitive than the normal tissues because most normal tissues are not going to be dividing, whereas the tumours are supposed to growing. Now some of the altis are going to be dividing rights such as the skin, the mucous membranes, and those are the ones that are going to be associated to breast effects during or just after reggata treatment. There's a small note on dosing in radiation therapy.

The same way we will talk about milligrammes per kilogramme driving an antibiotic. We are talking here about greys, which means d of Energy absorbed per kilogramme of tissue. We will also divide the total dose that we are administering typically in, in a number of fractions.

A fraction is a specific treatment, so every time we give regular therapy to the patient, that's called a fraction. The reason why we divide this total dose in a few fractions is because it does help with the tolerability and the efficacy of treatment as I will explain in the following slide. So why do we fraction it?

And that is because of the four R's of radio biology. First of all, we fraction it because it helps protecting the normal tissue. This is because if you give a very high dose of radiation at once, then it's gonna cause a lot of damage and it's gonna cause a lot of problems that are gonna be unrepairable.

But if you do give a small dose of radiation and then wait for at least some hours, mainly 6 typically 24 hours, until you give the following radiation, the normal tis is going to be able to repair all this damage or a significant amount of the damage during that time and therefore, you're going to be able to spare the normal tissue a significant amount of damage through fractionation. The tumours don't have the same capability of repair, so theoretically you're obtaining the benefit by fractionating because you're building up a dose in the tumour that you're not building in normal tissue. Also, you're going to make the tumour be more sensitive to radiation due, due to fractionation.

This is because tumour cells are not all going to be in the in the same cell cycle. Some of them are going to be in phase M, some of them are gonna be in phase S, and every phase is gonna have a different sensitivity to radiation. So if you did only one dose, the problem is going to be that then Only the cells that are in sensitive phases will die.

But if you find the more fractions, it means that basically the ones that haven't died because we're in a resistant phase and they will have evolved into a more sensitive phase later in the treatment and will be sensitive to radiation then. Also, oxygen is very important for the tumour to respond to radiotherapy and some tumours will have some areas that are hypoxic. Either because they have vessels that from time to time are not bringing blood, so sometimes they will be bringing blood to the tumours and sometimes not just because the vasculature of the tumour is so abnormal or just because the tumour is so large that the vessels can't get far enough the oxygen for the tumour to be fed.

So if you divide these in multiple fractions, potentially gonna be drinking during treatment and therefore an area that was hypoxic will not be hypoxic later. And also some of these vessels that potentially might not be functioning well at the first fraction may be functioning well later in the treatment, yes, because they are dysfunctional, they, they don't work all the time. So because of all of these, basically the tumour is going to be reoxygenated and therefore the treatment is gonna be more effective in those cells that were not oxygenated adequately on the first fraction.

We are going to talk now a little bit about acute toxicities. So acute toxicities in radiotherapy are those that occur just after treatment or during treatment, typically at the end of treatment. They occur because of damage to rapidly responding tissues to those tissues that are repopulating all the time, just as the skin or the oral mucosa, so those are just renewing all the time.

So basically, if they are not in the field, they might not be present. For example, a dog with a brain tumour because the tumour is quite deep, you might spare completely skin and you will not have any adverse effect. But a dog with a scar being treated, obviously it's going to have more toxicity because you're, you're treating the skin, you're giving a high dose of the skin.

What does this depend on? There are some areas that are going to be more sensitive like the path, for example, or areas with high motion, like for example, the axilla, but it mainly depends on the total dose. So if you give a relatively low total dose, the acute toxicity is going to be mild or not present, but if you give a high total dose, it might have severe acute toxicity.

It is going to cause discomfort to the patient, and during this time you need to prescribe analgesia and supportive care and recommendations to the owner to make sure that the patient is getting adequate care and the site will heal nicely. However, this type of toxicity will typically resolve within 1 to 3 weeks from completing the treatment and therefore, it is not considered. Very self-limiting.

It's not the major factor that makes us decide. It is definitely a factor but it's not the most concerning one. What things can we do to make this process easier for the dog?

First of all, when the eyes are in the field, we will always recommend doing eye ointment to keep the eyes hydrated, to protect and to reduce the risk for any observation, which is very uncommon nowadays in in dogs receiving regular therapy equipment if it's adequately prescribed and if it's adequately planned. For the skin, we will frequently, recommend some types of, of topical treatment either a topical gel to protect from the skin that is exposed, or sulfurizing cream because of its antiseptic. Nature, if the owners ask, can we, can we scrap the area?

Can we cleanse the area? The answer is definitely no because those cells that are growing, they are very sensitive, but they could definitely if it's a small one, like if it's a small dog, for example, in the bath to, with lukewarm water so that they can just walk a little bit around the bath, because it sometimes makes them feel better. However, if they do this, it's important to, to dry the with air drying, not with like a hair dryer or with a towel, just let it dry by itself, so there is no rubbing at all.

The area should be protected if the dogs, for example, are going for a walk. You want to put like a little shoe or something to cover the area if needed. However, you don't want to leave the bandage for a cover all the time because it's the tissues were oxygenated and it's also better but you don't want to, to have the, the constant having.

We sometimes we use oral washes for dogs that have Radiation given to the oral cavity if it's inflamed and these oral washes are a combination that we create in pharmacy basically combines oral like a, a topical analogues like lidocaine with an antifungal or an antisecept. And the owners will just with a syringe syringe at home every few hours, and it's not always required, but it's something that can be added and in some cases help if needed. With these cases, when, when we are expecting severe acute toxicity to occur, we typically are very proactive at escalating the analgesia, and being prophylactic, so we will start potentially a non-sal anti-inflammatory even before there's any evidence of, inflammation on the site.

And then, the more it progresses, the more we increase it. Tramadol has been shown to be quite ineffective because of the fact that dogs don't seem to achieve adequate levels of the metabolite that actually works. And so we don't use it in dogs anymore, but we do use it in cats sometimes, although they frequently will hate the taste, so it, it sometimes works, and sometimes it doesn't work.

And all the drugs that we can potentially use are gabapentin, amantadine, fentanyl patches are really work, really good, like they work very well. The problem is that there, there is some trouble with the drug abuse risk and therefore we try to. For, brain or spinal cord tumours, we will frequently prescribe steroids which can help in potentially preventing any potential inflammation of the site, obviously we don't use concomit nonal but it's OK, but no other non-steroidals.

Also, we don't recommend using prophylactic antibiotics even when the skin is expected to, to break down and that is because they have shown to promote multi-drug resistant infections, you don't seem to reduce the risk for worse adverse effects. When we do use antibiotics, we take a sample for culture to just make sure that the antibiotic that we're going to use is actually going to be effective. Buster colours will be very important if there's gonna be severe adverse effects in the skin to avoid the pets to be leaking at the site.

It's also important to make sure the other pets are not leaking at the site because that infection. And during the time that the site is recovering, especially, . It's not really hard to where I am because I, I actually am based in Scotland, but in some areas of the UK or even in Scotland sometimes you have some sun.

So, it's important to avoid that, that sun exposure, for, for a significant amount of time because it could potentially, worsen the, the icity. So no sunbathing during the period of recovering from acute toxicity. For those dogs or cats that have oral tumours and are having radiation therapy, given to the oral cavity and aesthetic because by the best effects, using wet food is better to try to avoid Damage from from the foot itself and heart to should be avoided as well.

This really applies to any patient that has a neural tumour painful anyway. Something interesting is actually that cats do tolerate have the from the toxicity point of view, so it's unlikely that with the doses we use we would see severe toxicity in cats, whereas we, we sometimes see it in definitive intent protocols in those. That was about acute toxicities and now we're going to talk about late toxics, which are the other group that is also very relevant to know about.

And this occurred because of damage to the slowly proliferating tissues such as connective tissue or bone or nervous tissue. They are not seen shortly after shipment, but the sooner they're seeing is within months, typically, sometimes they're seeing even years after. The most common ones that we see are permanent cosmetic changes.

Sometimes they're not permanent, they are, and this would involve, for example, alopecia of the site that has been irradiated or change in the colour of the hair or change in the colour of the skin. So there really is cosmetic. There are aesthetic, adversaries that shouldn't really have any impact on the patient's quality of life, but it's important to mention clients.

However, there is a potential for more permanent and serious dangerous life-threatening adverse effects. They are very uncommon if you prescribe adequately the treatment. So we, this is the, the main focus we aim at when we are prescribing treatment and, and planning a treatment.

We're focusing in minimising the risk and below 5% within 5 years for the patient. So, so it's very rare, but yes, it can be very severe, for example, if you. And there's always a reason it should be mentioned to the client that this can occur.

Secondary malignancies can occur from radiation as in humans. The risks not be, you know, below significantly below 5%, especially below 1% for if taking to control the patients, maybe a little bit higher risk if you focus only on your own patients because the more time that goes through the, the higher the chances for the cancer to develop secondary radiation. Other problems would be, for example, a fistula connecting the oral cavity and the nasal cavity that could potentially be associated to chronic rhinitis or to infections, and also cataracts that blindness, osteonecrosis that could cause fractures of bone or necrosis of the brain that could cause uncontrollable seizures.

So because All of this can be life threatening and may not have a good solution. It is important to minimise the risk, and for that, what is very vital is to limit the amount of those given per fraction. We know that for late effects it's very, very important to minimise the dose per fraction because as I said before, in fraction and fraction, these normal tissues and basically repair most of the damage and minimise the risk to a very low rate.

The pathophysiology behind the these damages typical damage of vasculature that irrigates the tissues or to loss of normal tissue . Stem cells. So now that we have spoken a little bit about toxicities and we understand the toxicities of radiotherapy, we can explain a little bit better which type of protocols we can use.

The first modality for which we can use with therapy is for palliative care, basically, and we typically will do these in dogs that have advanced disease or if the owners don't want to consider. Because it's palliative, we don't want to have the dog go through a time where he's having or she's having or the cat having discomfort from radiation and therefore we minimise the acute toxicity. How do we do this?

We basically limit the amount of total dose that we are giving. We give a lower total dose and therefore, typically these patients will not have any adverse effect that we only have mild adversity. Acute effects, I mean, just have to treat.

Because we also don't want the patient to have to come very often, we will not be giving a lot of doses. We typically will give bigger fractions, but only a few treatments, 345 treatments that can be given either once daily for a week or weekly for a few weeks. Because we're giving higher dose per fraction, there's gonna be a slightly higher risk of late toxicity into account, especially if the dog is thought that to be going to live for, for very long, although, as I said, this typically is more for final stage diseases that in dogs that are unlikely to live for longer than 1 year or, or 6 months.

So the risk for a clinically relevant latex is this is still quite low. It's a protocol that is consisting of only a few fractions. The cost associated is typically lower.

Compared to a definitive index. A great example for palliative art, a great indication would be an ado with an. Most dogs with ostosarcoma will have great relief of pain, and ostosarcoma is actually a tumour that is known to cause a very, very severe pain in humans and it is thought to cause very severe pain in dogs as well.

And radiotherapy is thought to be the second best way of dealing with this pain, being the first one surgery. Obviously computation would be the first choice, but if, a dog is morbidly obese or if Or cat has only three legs, or if a The onus is declining amputation then and radiotherapy is considered a very good way as an alternative. First of all, this is Kyla.

She's a nine year old Labrador that presented with a distal radius osteosarcoma diagnosed by a final aspirate. The owners did not want to consider any type of surgery for her and they then opted, . For radiotherapy.

She, one of the reasons was that she was, she was very overweight. So basically, we combined it with pomidronate, which is a bisphosphonate which inhibits the osteoclast proliferation and it also Acts as a painkiller for, for bone cancer with some oral analgesics. She had a great response.

She basically went back to normal, she was not weighing, not weight bearing and I started using the leg again. This is just a picture of, of showing how, how we treated her. So this is a manual treatment, and basically we do manual treatments where we don't have to do a CT scans, so obviously it's cheaper as well.

When the site that we're treating is on, on a leg, for example, because there is no areas that are of concern around like the eyes of the brain and because the area that we want to treat. The clothes hangers are used to, you know, you can just use any hanger to pull the skin away but you can save some of the lymph of the skin. And the yellow material that is put on top is called equivalent material and basically it's placed there because we want the whole thickness of the, of the limb to receive those and radiation is to go through something too fresh for delivering the boats.

Now again, she did very well. She had a very marked response and she was coping very well for 9 months. After that, the stopped working and basically, the in.

Reappeared again. Typically, if we hadn't done it with analgesia only the, the survival time are in control seems as 1 to 3 months. So it was already a really good response, but at that stage, the owners wanted to try a little bit more because it had worked for 9 months.

We decided to give it another go and her confound and 5 months later, again, it worked, she improved a lot, but 5 months later she presented with. To onset lameness and as you can see in the picture of the right, she presented with a pathologic fracture. This is something that is not uncommon, especially for dogs that enjoy a very prolonged response and this is because the tumour can still predisposed.

To radiation necros to, to, to a fracture, but also because the treatment itself is going to create post radiation necrosis radiotherapy. So it is relatively common in dogs that do very well and enjoy a significant amount of pain-free survival. Although most dogs will respond significantly to radiation, this response is not typically as prolonged as in Kayla, and they will, as a medium, enjoy a few months, like 3 to 5 months life after radiation.

However, in some dogs like Kayla, the, the, pain relief can be achieved for a year or even longer. Something that is very interesting of dogs with osarcoma is that when you don't remove the primary tumour, the chances for early metastasis are much lower. We think this is because the tumour is sending a signal to the micrometastasis in the lungs saying, you, you can't grow because I need all the nutrients for myself.

That was the case of Kyla, for example, 14 months post radiotherapy, she still hadn't developed metastasis site. This is another case. Luisi also underwent palliative therapy for Anaosarcoma, and again, She enjoyed a few months of good quality of life for 8 months, about 8 months post-treatment, the tumour was growing and the owner selected for surgery at that time, but they did not elect for any chemotherapy.

So what happened 3 months after amputation, the lung was full of metastasis. So just an interesting point, to discuss about osteosarcoma. This is another case of sarcoma, a very different one.

This is gipsies. It's a geriatic, Jack Russell that presents with a big aggressive mass, on the maxilla but goes into the nose and also into the oral cavity to, the heart palate. Maxillas sarcomas are very aggressive tumours and, therefore we opt for a palliative rapy protocol.

The image in the left is a 3D reconstruction of the treatment and the pink area is actually the area that was receiving. Here we can see some CT images, so you can see that the nasal is completely distorted. The left side is is filled by this tumour that is also going through into the subcutaneous tissue and into the oral cavity.

And you can see a picture of the mass from inside the oral cavity as well. We gave 4 fractions of treatment once weekly for 4 doses, and surprisingly, you can see how the tumour is shrinking even during treatments. You got a great response and tumour control for very long, 10 months post her T site was still looking great and she was having a great quality of life.

She did develop a little bit of inflammation in the skin, but it was very short lasting, and she didn't get like any late toxicity from treatment either. Unfortunately, nearly a year and a half after diagnosis, she died from a metastasis in the lumbar, vertebra. She presented with neurological signs and at that time, the owners decided it was time, to, to, put her to sleep, but she did get a really good quality of life for, for a year and a half.

So now we have discussed a little bit about pality and we're going to go now to definitive, definitive. And this is a completely different story, but we use definitive in IT in patients in which we want to achieve long-term control or in which we think we can achieve a cure. And because of this, we want to give the highest dose that we feel the patient can tolerate or which we will have to decrease the dose per fraction to a smaller amount so we can build up a high dose of the tumour.

Because of this high so dose, the, the, the expectations will be that if there's a skin or mucous membrane involved in the field receiving a high dose, there is going to be significant acute toxicity. There's gonna be moderate to severe dermatitis or mucositis that will resolve within a few weeks. But if we feel that patient is gonna live for years after treatment, then we feel it's worth to, to consider this a small period of discomfort that will be palliated with painkillers anyway.

Because of the longer period of and higher complexity of treatment, it is typically associated with a higher cost, and it's typically even daily, during 3 or 4 weeks, although some practises in the United Kingdom will give it on a Monday, Wednesday, Friday basis, but it's typically more because of limitations with the anaesthesia team rather than because it's more benefit. Because of this lower dose per fraction, there is a low probability for late toxicity even if the dog lives for very long. So there are 3 ways of considering definitive radiotherapy.

It can be given as a single modality for microscopic disease, and it is actually the The, that's the treatment of choice for brain and nasal tumour in the opinion of most many oncologists. On the other hand, it can also be used as an adjuvant treatment. So basically that is used in infiltative tumours such as muscle tumours or comma, stomach carcinomas in which you can't or you don't want to do a big surgery like an amputation.

You remove the growth disease, but you then want to kill the rest of the cells that are invading the subcutaneous tissue and therefore you follow it with, with radiotherapy to kill those cells. Sometimes instead of doing adjuvant radiotherapy after the surgery, we will do new adjuvant therapy, which basically means that you give radiation before surgery, you basically sterilise the margins of the tumour and then you do a more marginal surgery. We see this especially in a small patients with large tumours like for example, cat injections cells and comas, because if you do it the other way around, you sometimes end up needing to irradiate half of the body of the cat, which is obviously not very feasible and, and risky and much more complicated.

But it has some benefits as well because for example, with neoadjuvant therapy, there is less risk for sitting during surgery and it's it's not to me it's the area where the tumour was because the tumour is like. So I want to briefly describe what do we need to do when the tumour is located in an, in an area where we can't see or when there where there is a lot of organs at risk in the area. So before for Tyla, the job with the comma, we were doing manual plannings.

We were basically planning the and calculating the dose on the day of treatment on the table. But if the, if it's a brain tumour or nasal tumour or a tumour in the thorax, then we will be doing most likely a computer-based plan because it's going to be safer and it's going to be more. So we first have to do a CT scan, but it's not a normal CT scan.

In a CT scan, we have to the patient in a very specific way. We use immobilisation devices. So that we can replicate the position on the.

So on the top left, we can see a cat that is being positioned in a device that is like a mattress where you can sat here and it basically gets the shape of the patient and then it becomes hard and it's hard all the way down until you complete the treatment, then you can remove the air, put the air again back again, sorry, and, and then you can reuse it. On the picture of the bottom left, we can see a dog with a brain tumour for which we develop a mask, basically, a thermoplastic mask which can be malleable, it's hard, then you hit it, then it becomes malleable, then it gets the shape of the picture and then once it's dry, it gets hard again. This patient also has a bite, mould you can see inside the mouth that the oral cavity is filled with soft tissue, attenuating material, which is basically a material that you can can hit, and you can then shape it to the teeth, you can fix the macula and the mandible in every treatment and basically, once it gets cold, it, it gets hard.

So once we have obtained those images and we import them into a computer that is specialised that has special software and then we have to consider side by side the different organs at least for example brain as you can see here in yellow, the eyes so we can train them and that we can evaluate how much those are receiving and if it is safe. And then also even more importantly we have to in the tumour which is basically the. Red line in this, image and also we then add a, a special margin just for errors and if the patient wasn't or if it moved for some reason, and also for a margin of infiltration of the tumour into normal tissues that would be the incline.

Once we have done that, and that is the 3D reconstruction of all the contours. Once we have done that, then we have to plan the treatment. We have to decide which angles we're going to choose for the treatment, and we basically combine these to create high dose in the tumour and to minimise the dose in the.

In the, in the normal tissue. You can see in the graph on the upper right that significant differences between the tumour and the normal tiss. So the red and the pink are the tumour size, whereas all the other lines are.

The, the normal tissues and basically this is, this here would be 100% of the of the organ which would be the tumour in this case is getting 100% of the dose versus this would be 0% of the organ gets 0% of the dose. Here you can see, those colour wash, the red would be the highest dose and then, as long as it's getting colder, it's getting more blue, and these lymph nodes are being treated as well, but you can see that all the normal organs have minimised those things to be computer planning. Once you have done the plan is already, then you just need to position the patient on the table, and you need to position the patient on exactly the same position using the mobilisation devices.

And you can take an image to compare with the position in which the patient was on the CT scan and in which the treatment is going to be based on, and if everything is OK, then you can treat. So I just wanted to give you an example of a dog with Definitive intent treatment. This is Ola.

He's an eight year old French bulldog that presented with scissors. We did an MRI and that showed contrast enhancing lesion in the olfactory lobe, which was most likely a glioma. Gliomas are tumours that with no treatment or with only palliative care like analgesics and anti medication and steroids have a prognosis measured in weeks to 2 to 3 months depending on how long, but it is a very aggressive tumour.

However, with radiotherapy, you can achieve survivals of even a few years in the, in the best case scenarios. In her, we opted for a definitive RT protocol, so that's 20 fractions of 2.5 grey.

And also combine this treatment with obviously antisocial medication analgesia and steroids. He improved significantly clinically even with the medical check. And she didn't develop any adverse effect from radiotherapy other than from the steroids, which is very typical for brain tumours.

They don't typically develop an acute from treatment. 3 months later, we repeated the MRI. You can see the images of the top are the ones that diagnosis and the images on the bottom are the ones that 3 months and you can see how the mass is not visible anymore.

There's only like some small changes, but there was definitely a very significant shrinkage. Until 2 years later, Lua was doing really well and she had no signs of tumour or of toxicity whatsoever. Unfortunately, 2 years later, she did develop new clinical signs, so we repeated the MRI to find that the tumour had regrown again.

The owners were very motivated. And they really wanted to try to beat them, but because it had been such a long time, we felt probably the normal tiss had repaired significantly and we have given her another full course of radiotherapy. And now it's been 6 months since that time and she's still doing really well.

Last week I spoke to the owner and she's still being her normal self. But this outcome is relatively common. It's not uncommon for, for dogs with biomma.

Sometimes obviously some can do worse, some some can do even better. And it's definitely very rewarding to treat brain tumours. There is a risk for late toxicity as I said before, a little bit less than 5% of them, with safe protocols will develop radiation necrosis of the brain which can cause severe, seizures which are hard to control, but that is a minority and sometimes it can be really hard to know actually if it is an adverse effect or is the tumour coming.

This would be another example of definitive intent treatments. This was a dog that had high grade soft sarcoma and she had had recurrence multiple times after surgery within a few months. So the owners didn't want to amputate and they finally opted for radiation therapy.

The sight you can see is initially, very angry, but after a few weeks it heals nicely and we can see in the last how the skin is becoming more pigmented and black. This dog, her name was Leila, she, actually, Lola, sorry, her name was Lola. She actually developed recurrences finally 4 years after, radiation.

Which was significantly longer than the previous times with without without radiation proving that the help of, of ra have been in reducing or delaying the, the risk of, of local recurrence. And here we have, we had, we have a dog with a nasal tumour which is also very frequently treated with radiotherapy, as I said before, treating those questions for this type of tumours and of all or most dogs will have a major clinical improvement with either palliative function protocols. This dog, her name is Tammy, and she actually got a definitive intent treatment and she was presented initially with epistaxis and, and with, out of sneezing and she had a marked improvement after treatment.

You can see how initially developed a little bit of inflammation. It can be because of the high dose for two weeks because it was completely healed and actually in the long term, 2 years later the hair had grown and she, she lived for, for a few good years without medical science and without significantly either, but she was a happy case as well. I wanted to talk as well a little bit about the stereotactic reggae.

This is a very novel way of beating. Cancer in Europe. It has been going on for a few years in the United States and for a little bit longer even in humans.

Basically, it consists of using a very novel system to be able to, to spare the normal the completely. It's a very precise system. You have a, a some type of imaging modality that is very advanced so that you can make sure that you are mimetrically positioned well in regards to, to the tumour and you also can manage to with very expensive and, and advanced computer software and machines, you can be very sharp on the gradient of those.

So there is a very sharp. From where the tumour is to where the normal tissue is and therefore with this you can give a very high total dose but only in a few treatments so you can basically get the two good things of both sides and spare the normal tissues, but you also can give only a few fractions and still be equivalently effective compared to in treatment. Now, ideally stereotactic period that should be only used for small and rounded patients because otherwise it can start being dangerous and this is how it is frequently used in humans, in, in many places.

However, in veterinary medicine because of the fact that it obviously helps a lot to only do a few fractions, it is becoming very fashionable to, to consider it for even inulsive tumours like nasal tumours or, or comma even. In, in LA, and that depends also of the radiation and qualities. I think it's important to know about this technique because it's availability is coming to the UK.

We already have a linear accelerator in the University of Edinburgh that can do this, and we probably will be offering this this . In the next few months and probably very motivated owners will be willing to travel from other parts of England if it is an ideal candidate. And also in England, it is going to be probably available earlier at some point next year at the practise of Southfields that is a very modern linear accelerator as well.

These are just a few papers describing the use of stereotactic therapy in multiple types of tumours including brain tumours, appendicularrosis sarcoma, or nasal. So, as a summary of what I've been discussing, for the last part of the talk, we have 3 main types of, of protocols. We can have definitive therapy protocols which basically are aimed at giving a long-term control of the tumour.

For that, you give a high total dose, but to respect the normal tiss, you have to, to divide the total dose in very small fractions, and typically that involves 3 to 4 weeks of daily. And these treatments are expensive. They are associated to potentially acute toxicity if it's gonna be involving the skin, if the dose is going to go to the skin, but the resolve in a few weeks, but they're typically very safe for the long term, and they can definitely be worth it for the right cases.

In case the tumour was controlled for a significant amount of time, 1 to 2 years, for example, for a nasal tumour, but then the clinical senses relapse, then typically although it depends a little bit on the location of the tumour, and there has been enough reparation of the normal tissues and it can be. If it is so that it will be worth for the, for the patient. They typically work again, but they don't work to the same extent.

The, the span of the effect will be lower. For stereotactic therapy, this is the, this is a new modality. It refers to a technique that uses very advanced, technology and it's extremely precise.

It basically burn the tumour and spare the multicules that are just in contact with the tumour. It is more ideal for small and loaded lesions, but it has been used and it is being used in the, in the states for multiple inductive tumours as well. And the studies that have been done so far have shown acceptable toxicities and, and a relatively comparable results compared to like more definitive and, and prolonged.

And that is a modality that will be offered in the United Kingdom potentially in the next few months, that would be 1 to 3 treatments. And then finally palliative therapy, which is a very handy type of, very well tolerated in the short term. It has a little bit more of risk if it well.

This is still relatively low for, for clinically relevant late CCTs, and it can either be given once weekly, typically for 4 weeks, or sometimes there it's given twice weekly for for 3 weeks or once daily for 5 days. The latest protocol in the list that's . Once daily for 2 weeks that he's considered by some, but by some it's actually considered a definitive fact.

So, after going through that radiotherapy in cancer, let's talk a little bit about radiotherapy in benign conditions. So radiotherapy can be used because of it, of its inflammatory and inflammatory effects in some conditions that are re refractory to the normal treatment. For that to make sense, the there's a few rules that need to occur.

So first of all, the condition needs to significantly affect the quality of life of the patient. That obviously even if radiotherapy is overall safe, you're going to be exposing the patient to a risk. Second, the condition needs to be refractory to the conventional or standard treatment.

For example, if it was a dog with osteoarthritis, and first of all, the dog needs to have severe enough to make it worth it to for treatment, so it may be, it needs to be impacting his quality of life. But second, it needs to have stopped responding to anti-inflammatories or to other multimodal therapy that is typically used in general practise. Third, the protocol needs to be there or very little risk to the patient because obviously these patients with benign conditions might have even better, much better Therefore, the doses that we give are typically anti-inflammatory, but they're lower and they're very safe.

Which conditions can be considered for this. So there have been multiple papers called multiple conditions. First of all, It has been proven to be very effective for dogs with degenerative joints.

This is most of them. Will improve temporarily with a million of even 1 year or more of quality of life. It can be repeated in them.

It can be used for multiple joints, so it's definitely something to explore and to compare for those dogs and in which medical treatment is not working anymore. OK, in addition to that, in Switzerland, they also frequently use it for many encephalitis of unknown origin, for either refractory cases or for drugs in which the owners don't want to give any type of chemotherapy like cytarabine, for example, and it also works really good. It works in most of them for that we have to really the whole brain, but we give it to a dose where it is very tolerable and it doesn't seem to have major impact on the quality of life of dogs at any point.

It's also been used for yo cell and for Scottish fold osteochondral dysplasia, effectively. For silo cells it's been used when for, for those cases in which surgery was not effective in which there was, there were refractory cases, although it's probably An uncommon situation. It's more uncommon than the others.

And another thing in which we have been using it from time to time that in which it can work really well is for lymphoplasma cytic rhinitis, especially in cats, but also in dogs, that doesn't respond to medical management. We have some really good responses sometimes. Something that we might be looking into in the future is consider we, we have to dentistry and to have their opinion, but potentially, for cats with gingiv stomatitis, that is not responsive to surgery that could be consideration as well because of an inflammatory effect.

Radiotherapy is an effective palliative treatment for dogs with late stage disease in which creative intent treatment might not be indicated. It can reduce pain significantly by inducing anti-inflammatory effects, but also by reducing the tumour burden often, like in the case of Gypsy that we saw, . The tumour, the tumour control is not really the main goal of this treatment modality, but in some occasions, even with palliative RT you might achieve long-term treatment control as well.

Radiotherapy can also be used with curative intent protocols to achieve long-term control of cancers alone or combined with other treatment modalities such as surgery or chemotherapy. And the order of these modalities really decided on a case by case basis depending on the tumour, the location, the size, and the preference of the oncologist and typically it will be through close communication between the surgeon, and the medical oncologist and the radiation oncologist. As we mentioned as well, recent advances in therapy in human and, and veterinary medicine allow for more intensified protocols which basically consists of just 1 to 3 fractions, but very high dose per fraction to ablate the tumour but sparing the normal tissues.

This is ideal for small and rounded tumours, but it is being used for many tumour types in, veterinary medicine and so far studies are supportive of potential benefit of, of these, . Protocols as an alternative to others that are more long-lasting or less effective. They do need more research though in which we will compare hopefully prospectively, these different protocols to make sure that they are as safe or as effective as the more conservative protocols and, and, and these stereotactic therapy is going to be available very soon in the United Kingdom in the next few months.

Finally, but not least important, radio therapy can also be used to treat benign conditions, refractory to standard treatment, and the most common one we use radio therapy for is osteoarthritis that has stopped responding to medical management, but others such as me encephalitis of unknown origin or lymphoplasmocytic reinitis might also respond very well to radiotherapy. Thank you so much for your patience and for your attention. I just want to say thank you and share with you the face of one of my favourite patients who was very happy after recovering from her last fraction of radiotherapy treatment.

You have my email address in this slide, please feel free to contact me anytime for any question that you might have. Thank you and have a lovely evening. Bye.