OK, good evening, everyone. Welcome to this Thursday evening webinar for Webinar Vets. This is going to be with me, Owen Davis.
I'm an oncology specialist. I work at Highcroft Referrals in Bristol, and our topic for this evening is how to approach bone tumours in 2022. Now in designing this webinar, I realised there's actually quite a lot to say.
And I could potentially be talking at you for hours and hours and hours and you'll just want to kill yourself, so I had to decide what to include and what not to include. And in the end, I settled on this. I'm gonna give an overview of bone tumours and highlight some very important differential diagnoses, and I'm gonna present my approach to them.
I'm then gonna spend the rest of the session focusing on, by far the most common bone tumour, the primary bone tumour, that is the osteosarcoma. I hope that sounds OK. Without further ado, then we'll start.
And bone tumours commonly look like this, a bony swelling. With or without pain or lameness. And the pain or lameness can be very variable, and that can confuse you sometimes.
You might find a dog who's extremely lame, 100 lame at some point and then seems to be getting better. And don't let that improvement fool you. Because the mechanism of pain here is the intermittent occurrence of little cracks in the bone and subperiosteal bleeding.
And when these occur, the pain can be excruciating, but then the pain will will improve as the inflammation resolves slightly. It will just flare up again when the next incident like this happens. So don't let apparent improvement fool you.
When you get a bony swelling like this, I would encourage you to take a radiograph. Now, as we all know, a radiograph is not going to tell us a definite we have a bone tumour. It will identify an aggressive bone lesion.
And frustratingly, there is no one radiographic feature which will confirm the existence of an aggressive bone lesion by its presence and exclude the the existence of an aggressive bone lesion by its absence. So the diagnosis of an aggressive bone lesion is a judgement call that you have to make after considering several bits of radiographic information. And I'm going to go through the 3 most important ones now.
The first one is bone lysis. Lysis of the bone cortex is always much more significant than lysis of the medulla. Then you have to look at the pattern of the lysis itself, and the aggressive bone lesions will have permeative or moth-eaten lysis rather than geographic lysis.
I'll show you some examples of these. This is geographic lysis. You see, it's very, very well demarcated.
You can see exactly where it starts, and exactly where it stops. And this indeed is a benign situation, a bone cyst. Permeated lysis looks like this.
We have a scattering of little holes irregularly within the bone cortex. And when these are big enough, they coalesce and overlap with one another, creating the moth-eaten lysis, which consists of irregularly distributed and varying in intensity patches of bone lysis through the cortex just here. So it's permeative and moth-eaten of of the cortex that coincides with an aggressive bone lesion.
The second feature you need to look at is periosteal reaction. Now, you're certainly allowed to have periosteal reaction under benign circumstances, OK? The key thing that makes it a sinister finding in an aggressive bone lesion is that it's irregular, like we have shown beautifully in this radiograph here.
And finally, you look at the transition zone, the way the, the bone lesion merges into the normal bone and merges out again. And benign things will typically have a long or have a very short and well demarcated transition zone, and the aggressive bone lesions will have a very, very long and indistinct transition. If you look here, for example, You can't see exactly where the bone lesion stops and where the normal bone starts.
So these 3 features I think are the key things to consider whether you have an aggressive bone lesion. Sometimes, like in this radiograph, it can be a bit more specific. What we have here, as well as the irregular moth eater osteolysis, the irregular periosteal reaction, we see lifting of the periosteum just here.
And the triangle this creates with the bone is called Codman's triangle. And if you see that, that is highly suggestive of a bone tumour. Beware though that in our feline friends, you still have to use the same features to define an aggressive bone lesion, but you have to recalibrate your settings a little, because as you see here, look at this.
This is an aggressive bone lesion, and I think we'll all agree that aggressive bone lesions in cats can look very non-aggressive. You've got quite a well demarcated area of lysis here. Very, very minimal periosteal reaction.
You do have a long transition zone on one end, but the rest seems quite short. And that's, you know, as good as you get really. If you look at the orthogonal view over here, you'll see that the lysis is extreme and that's probably the biggest clue as to what's going on.
When you do a CT, you can see the extent of the bone that's just been eaten away by this, which is a feline osteosarcoma. So it's the same features in cats, it's just they're often much more subtle and often they don't tend to co-occur so much. So my key point then.
You can demonstrate an aggressive bone lesion radiographically using some or all of the following features permeative or moth-eaten cortical lysis, a long transition zone, and irregular periosteal reaction. Ultimately though, these features are not discrete, they're there or they're not type of features. They're often very subtle and continuous, and there's no level at which you definitely have an aggressive lesion and definitely don't.
So it is a subjective judgement call. Be also aware that the degree of radiographic aggression doesn't necessarily correlate with clinical aggression. And the absence of aggressive features, however, will make clinical aggression unlikely.
Let's move on. So aggressive bone lesions then are not necessarily tumours. The first thing you need to consider is that it could be bacterial or fungal osteomyelitis, and these of course are treated with antimicrobials.
Then you could have the primary bone tumours, and more than one type of primary bone tumours are available. Go osteosarcoma, where the best outcomes are achieved with wide local excision or amputation, and then chemotherapy. You have the chondrosarcoma, fibrosarcoma and synovial cell sarcoma where amputation is often all you need to do.
You've got the hemangiosarcoma where we typically talk about amputation and then some form of chemotherapy, but a different form usually to osteosarcoma. And histiocytic sarcoma where you'd need amputation or some form of local control and a different form of chemotherapy again. You've got tumours of bone marrow origin like multiple myeloma or lymphoma.
And these are often treated with chemotherapy only. And finally, you've got me metastatic disease to the bone, for example, from mammary carcinomas or you're a genital carcinomas. So the reason why I'm telling you all this is because the treatments and the prognoses differ.
Therefore, if you see an aggressive bone lesion, you need to have a careful consideration about what diagnosis is likely. To start with, look at your history and the animal's concurrent disease. Because the first thing you need to consider is, is this actually an infectious process?
And bear in mind some of these infectious processes can be important zoonosis. It's not very common, but the implications of missing these, particularly exposing yourself to some of these agents if you're to try to sample these lesions, that, that implication can be huge, can't it? So we need to get this right.
If you have a dog who has come from an area of the world where systemic fungal diseases are endemic, you need to consider this. Things like blastomycosis, coccidomycosis can cause aggressive bone lesions, OK? If your dog hasn't travelled outside the UK, I think these would be very unlikely.
In cats, however, particularly cats in the UK, we've got to bear in mind that a very important cause of an aggressive bone lesion could be mycobacterial disease after inoculation through a bite wound from a rodent. So, particularly in British cats, this is a very, very important consideration here and a very important zoonosis. Or other things though, if you've got an aggressive bone lesion, particularly in the lumbar spine, you might want to consider, could you have a urinary tract infection or a prostate infection or something like that.
And this is to really ask, have we got an infectious process? Next, you can look at breed. And we know that osteosarcoma tends to affect the big dogs.
Histiocytic sarcoma tends to affect certain breeds like the flat-coated retriever, schnauzer, Bernie's mountain dog, and if you get an osteosarcoma in a small breed dog, sorry, an aggressive bone lesion in a small breed dog, it's much less likely to be an osteosarcoma, but it still could be. It's more likely to be one of the other diagnoses. Than in the larger breeds.
Then you consider anatomic location. And osteosarcoma quite famously has certain locations where it has a propensity for occurring, that's away from the elbow towards the knee. And very rarely occurs in places like the elbow here.
It also is a metahosteal lesion. It tends to occur. At towards the ends of the bones.
The hemangiosarcoma is a diaphyseal lesion. That's because the nutrient horain runs into the middle of the bone. So the bloodborne cancers like hemangiosarcoma or like metastatic disease from other tumours tends to occur in the mid diaphysis.
If you find a tumour that has osteo has aggressive lesions on both sides of the joint like this. It's a useful finding because you tend to have two differentials, that is the histiocytic sarcoma or the synovial cell sarcoma. And here's another tumour that you can often pattern recognise, tends to occur on the head of dogs, and it's the multilobular osteochondrosarcoma.
This is one of the few tumours that you can diagnose pretty much definitively on a radiograph. That's because you've got these little islands of ossified bone. Amid a kind of sea of cartilage, and you get this kind of popcorn-like appearance like this, so it's a tumour composed of a bit of bone and a bit of cartilage.
If you've got multiple lesions, this can be very helpful as well, and I'll show you an example here. This cytology, on the right came from a Rottweiler with a bony swelling in a distal radius, very typical for an osteosarcoma. The cytologist wasn't able to call it though, and said, well, yeah, it might be an osteosarcoma.
It could also be a round cell tumour. I thought that sounded a bit bizarre. But when we did some imaging, I'll show you the shocking findings here.
You look at these vertebrae. Just try to count how many osteolytic lesions we've got here. The dog is peppered with osteolytic lesions all through the axial in the appendicular skeleton, and this was in fact the case of multiple myeloma.
Now in cats, the same principles kind of apply. For the bacterial or fungal kind of, Diagnoses that can cause aggressive bone lesions, be aware of mycobacterial disease. You know that could be a very big, a big thing in the UK.
And also be aware of multiple cartilaginous exostoses. These are defects in the endochondral ossification of bone and in cats, bizarrely, they tend to occur in the adult skeleton over one year of age. They tend to be an axial problem, but they can look very, very aggressive.
Out, out of the bone tumours, then it's usually a shorter list of diagnoses that comprise the majority. You know, 60 to 80% are osteosarcoma, and there's other things like fibrosarcoma, chondrosarcoma, hemangiosarcoma occur that are less well characterised. So we've now defined the aggressive bone lesion.
We've considered the likely differential diagnosis. The next step would be to sample it. Now This is best described by taking bone biopsies, but I, I rarely do that these days.
I often find I can get sufficiently diagnostic sample with a fine needle aspirate. To do that, I would encourage you to use a wider bore needle than you would to FNA a lymph node, for example, a 20 or 21 gauge needle. And use 3 to 5 mLs of negative pressure on the syringe to suck those sarcoma cells out of the lesion.
The sarcoma cells tend to hang on to each other quite tightly, so I often find you do benefit from the negative pressure. Now, a lot of the bone is hard. As you can see here, this white line on the ultrasound image is the tough cortex of the bone and that's not going to let the needle through.
But with ultrasound, you can see where the cortex is broken here. And so you can direct a needle in and using ultrasound to help find the right spot. And I find that's quite useful.
After I've done that, I always check cytology because you don't want to wait 3 days and spend 70 pounds sending this to a lab. Nor do you want to send this to a lab. We've actually got a beautifully rich cell sample here, but they've all been destroyed, in the suction process or the smearing process.
So check to make sure you have nucleated cells with cytoplasm all the way around. And this is a typical picture of osteosarcoma cytology. What you have is very pleomorphic, mesenchymal cells showing numerous features of malignancy.
For example, extremely irregular, nucleoli, a huge variation in nuclear morphology, very, very stled chromatin. And you've also got a large variation in the cytoplasm, and it's a cytosis as well. Even down here, you've got a couple of, you've got a cell that's multinucleated.
So this tells you you've got a malignant mesenchymal tumour. And the bone matrix, which is pink in the background. Can define osteosarcoma.
I'll just show you this picture for comparison. This is a more benign, or or rather well differentiated, mesenchymal cells. That's what these cells should be looking at, looking like.
And in the case of a malignant tumour, they tend to lose their spindle shape a bit. And often end up something like this. With irregular evaculation, multinucleated cells, etc.
So, the diagnosis of a malignant mesenchymal tumour in a lot of cases can be quite straightforward. In some cases though, you don't see the pink matrix to define osteosarcoma. And that's quite important, I think, because you could get some other mesenchymal tumours that might have a, a better or at least very different prognosis.
Having a good idea whether it's an osteosarc or not can be very helpful. And something that you can do on cytology that's very useful. Is an ALP stain.
This is relatively inexpensive and it's very well available, should be offered by most of the reference labs. If they, if you've got an aggressive bone lesion, malignant mesenchymal cells, and they're not able to tell you whether it's an osteosarc or not, you could ask for this stain which they should be able to apply quite cheaply, and it's extremely accurate. If you look in these red circles here, sensitivity, 97%, specificity of 100%.
And then the other one here, 100% sensitive, you know, so it's a good test, please use it. If you've not got an osteosarc, you might have a histiocytic sarcoma, and this is a cancer of round cells like this. They often look a bit like macrophages because that's what they are really, and they have a huge range of features of malignancy, as you see here.
And what do you think this is? This is a German Shepherd dog, a very ugly osteolytic lesion in the scapula. It's lymphoma It's a type of lymphoma that was causing nostriltic bone lesion.
So I check cytology in-house. I make sure I have nucleated cells with cytoplasm all the way around, and if I don't, then I'll proceed to take a biopsy. It's useful to take biopsy based on imaging.
And please make sure you biopsy at the centre of the lesion. You make sure you only go through one of the bone cortices, you leave the other intact, you know, because that can increase the risk of pathological fracture. And re-angle your needle after taking the first biopsy and take a few more.
So you need several at different angles to correct for there being quite a lot of necrosis within this. It's important though remember the centre of the lesion is where we biopsy an oncology. In dermatology, they might tell you to take the edge of the lesion, so you get some normal and some abnormal tissue, but for oncology, please biopsy the centre.
My second key point then. That an aggressive bone lesion can have multiple diagnosis and you need to sample them to find out. However, please use the signalment, the anatomic location and the presentation to help you refine the order of these differentials on your, on your list.
Fine needle aspiration is adequate in most cases to get a diagnosis, but sometimes you need a biopsy, and please be aware of zoonotic disease. And in the the colder European countries, certainly the UK mycobacterial disease will be a very important differential. So we'll talk about osteosarcoma now.
Osteoark Should be no surprise, it's the most common primary bone tumour in dogs. Risk factors for developing them would be giants and large breed dogs. And we know that certain breeds seem to be predisposed like Great Danes and Rowes.
But people have thought that height and weight seem to be more important than breed because it does tend to affect all big dogs, really. Some studies have shown that males are more likely to get osteosarks and neutered dogs have been shown to have a greater risk of developing osteosarcomas. It's generally a disease of middle age to older dogs, but tragically, there's also an early spike of incidents that's around 1.5 for 2 years.
I'll show you this, recent paper from the UK. It elaborates really on whether this is a size thing or whether it's a breed thing. In this graph here, we can see the body mass of the dog on the Y axis and the odds ratio for developing an osteosart on the X-axis.
And you can see that as the size of the dog goes up, roughly, so does the risk of the osteosarcoma. But there's a bit more to it than that. Look at the Rottweiler over here.
You know, one of the greatest risks for developing osteosarcoma. And significantly greater than an equivalent size Akita. For example, So yes, it is due to size, but there's also a very strong genetic component.
And actually in the Scottish deerhounds, 69% of osteosarks in this breed is believed to be due to a heritable trait. Osteosars most commonly affect the metaphyses, as we said before, of the appendicular skeleton, most commonly falling. And I've got the 4 most common sites here.
Towards knee, away from the elbow, and they also not uncommonly, they can occur in the distal tibia, just like the proximal tibia. We've got one here in the proximal tibia with pathological fracture. It looks dreadful.
And now I can show you some less common ones. For example, one here in the neck of the femur. One in vertebrae in the middle of the spine.
OK, this is absolutely dreadful. This is obviously affecting the ribs and causing a hemothorax. This poor dog had a nasal osteo yourself.
When this poor dog, the sinus frontal sinus osteosar. This dog had a mandibular osteosarc. And rarely you can get them at extra skeletal sites, like the mammary gland, subcutaneous tissue, intestines, and others.
Now these extra skeletal osteosarcomas are usually very aggressive. And on a few occasions, the occurrence of multiple osteosarcoma has been reported. And rather than metastatic lesions, this is believed to be a polyostatic phenomenon when osteosarcoma will occur synchronously in several bones in the skeleton.
This is not such an uncommon phenomenon in people or in horses, but there's only been a couple of cases noted in dogs, to my knowledge, polyostatic osteosark. So when we need to remember that osteosarcoma, as far as I'm concerned, is a very similar disease process no matter where it occurs. However, the speed at which it progresses and it's overall level of ferocity varies from location to location.
But in terms of the principles of treatment, for me, they're the same. We'll talk more about different locations in a minute. Once we've diagnosed an osteosarcoma, we'll talk about staging, assessing the extent of the disease in the body.
And I'll be aware that lungs are the predominant site of metastasis for these tumours. 90% are gonna develop mets in the first year of treatment. If you, well, if you don't treat them with chemotherapy at least.
Bone mets occur in about one case in 20. It's not many, but it can be a significant cause of pain. You need to be careful about this.
If you're thinking things like amputation are in order, you need to make sure there's not any osteolytic lesions in other places. 1 in 5 cases often come in with lymph node mets as well, and that's more than was traditionally thought. So when you stage these guys, you could consider 3 view thoracic radiography and abdominal ultrasound, or I would prefer a CT scan.
See far more pulmonary nodules on CT compared to radiographs. CT will also show much more osteolysis than radiographs will as well. I consider a very careful orthopaedic examination to help to find other sites of bone metastasis or even without metastasis to assess how good the rest of the dog's skeleton is, as in how well are they going to cope on three legs if necessary.
And they would palpate an FNA, any regional lymph nodes. So you can see CT section on the right versus the radiography on the left. You'll see mets on a CT scan down to about 2 millimetres in diameter, whereas it's usually about 6 or 7 millimetres plus on a radiograph.
So my next key point then. To stage an osteoarc because a number of these cases, 20%, can go to lymph nodes. I think it's important to image both chest and abdomen if you can, and also to get some good imaging of the bones, and palpation of the bones if you can as well.
So CT would always be the preferred motality because you get much more soft tissue detail, bone detail, and you see smaller lung nodules. If you can't do CT, Wouldn't make anyone feel bad about that, because most of the prognostic information we've got is from an era when CT was rare. And these cases seen at vet schools, which are staged with thoracic radiography plus minus imaging of the abdomen, and they're still the studies that dictate the survival time when you have, metastatic disease, for example.
So we might have a peculiar situation with the CT where you see very small lung nodules, you know the nets are there, but these lung nodules would be too small to see on a radiograph. So what do you call that? Do you call that the metastatic case, which is going to have a poor prognosis in the order of months, or is it the non-metastatic case that might live up to 18 months?
We just don't know how to deal with this information at the moment, but as years go by, the utility of CT will be better evaluated. Right. Let's talk about treatment of bone tumours now.
When we're talking with clients. I think it's easier to talk, to tell them, you've got two problems here. It's not one disease, it's effectively 2.
You have to do something to deal with the pain. And the potential fracture of the bone, OK? The local therapy on the local disease.
So this is important for pain relief and first aid measures. Then you have to do something to try to retard the development of metastatic disease, and that's really the proper treatment for the osteosarcoma. We need to stop the seeds of metastatic osteosarks from germinating.
This sounds kind of obvious to you and me, but to a lot of clients who are perhaps not biologically minded, I think this can be quite helpful. So most osteosarcomas are appendicular, they occur in the limbs. And so the most common and most effective local therapy is amputation.
If you amputate the leg. You will remove the source of pain and a potential fracture. And I think we all know that most dogs will do very, very well with this.
But it will be 3 to 5 months before metastatic disease in the lungs crops up and becomes life limiting. Now if you take off a thoracic limb, you should really include the scapula. And pelviclimatic amputation should be performed with coccofemoral dysarticulation.
The proximal femoral osteosars, we'd recommend an unblock aceabulectomy or a subtotal Melvectomy, just to make sure you're observing good oncologic practise. However, there are some cases like scapular osteosars and ulnar osteosarcs that can benefit from a limb sparing surgery where you just remove the bone that's affected. Might be easier said than done sometimes.
For example, you need quite a dorsal location on the scapula to be able to do this because you need to leave the bottom of the scapula in situ to have stability to the limb. And the ulectomy cases can do very well as well. So for these odd locations, think of things like that if possible.
And for the axial cases of the ribs, vertebra, calvarium, if you can, wide local excision or radical surgery would be the way to go. As we said, after we've done the surgery, please send the tumour for histopathology because, you know, it may not be an osteosarcoma. In unusual circumstances, despite what the preoperative tests have said.
And also we need to look at things like complete civiccision as well. Understandably, a lot of clients would be very upset with the idea of amputation and may need to give this an awful lot of thought. And a website that I think is very useful is this forum run by dog owners, poor dog owners, to support people where amputation is being considered as a treatment for their pets.
It's called tripods.com. You don't put www in front of it, it's just tripods.com, and they've got lots of really nice videos a bit like this one.
Where you can see three-legged dogs and sometimes cats charging about and having a good time. When you look at this dog, it takes a while before you realise that you've only got 3 legs. You see that?
Missing left hand. So I, I don't think I need to enforce the message to a veterinary community that amputation works and it's a really good treatment. Now, In recent years, we've asked the question, can we do any better?
Can we spare, the limb, remove the tumour, but keep the dog on four legs, and that's where a lot of really clever limb sparing surgeries have come about. The bottom line in my opinion is that limb sparing surgeries have got limited benefits or are frankly inappropriate for most dogs. They could, however, be beneficial for dogs with preexisting severe orthopaedic disease or neurological conditions.
In other words, those who won't tolerate amputation. The right tumour. What do I mean by that?
Because of the complexity of a lot of joints, there aren't many anatomic locations where a, a limb spare is gonna work. However, the, distal radius, which is the most common site of osteosarcoma, is the principal region where living spare seems to take place. And you need to catch it at the right time.
That, I think, is a big one. A lot of these tumours present when there's a huge amount of swelling and bone destruction, and you simply can't remove enough tissue to excise the tumour completely and maintain a connection between the proximal part of the leg and the distal part of the leg. So the cases that have limb spare that I've seen that have done well tend to be those that were picked up incidentally when the dog was being radiographed or examined for completely different reason.
So to summarise the requirements you might need before referring a case for limb spare. It's mostly distal radius. Potentially the humerus or the tibia.
You need to have a non-metastatic case for people to take the case on. The metastatic cases, as we'll see, we'll have a much poorer prognosis. It's just not considered worth all the, all the aftercare.
No pathological fracture, affecting less than 50% of the bone on radiography, that's a big one. Most of the ones we get just walking off the street in an average clinic will affect more than this. And minimal involvement of the surrounding tissue.
So if you've got a sizable swelling, you can bet your bottom dollar that there will be too much involvement of the surrounding tissue. So this is a picture of a limb spare. It, a lot of the techniques now involve a bespoke implant that is kind of made specially out of titanium, or 3D printed based on a CT scan of the affected leg and using the other leg as a mould for how things should be.
So you can see here an implant in the middle, plated on on either side, and as I say, it can work very well if it goes well. But these endoprosthesis techniques have a complication rate exceeding 50%. OK.
And they don't get you any different survival as well. You've still got your second problem, the spread of the osteosart, to deal with. The kind of complications you can see would be tumour recurrence, a very, very big one.
Because you just can't remove enough tissue to spare the connection of blood supply and lymphatics to the distal limb without leaving a bit of tumour intact in most cases. You've got very, very unhealthy tissue that you're trying to operate in, so it's unsurprising then that you can get things like infection or wound breakdown. You may get plate breakage or pathologic fracture because the implants the only thing taking the dog's weight and you can also get loosening of the implants associated with any of the above or just on its own.
So a lot of the limb spares do end up in amputation later. However, this is a video of the day after a limb sparing surgery. And it's quite nice to see.
You've got a dog, he's putting weight on the limb. And he's well well out all chased. And that looks like a nice solid repair there.
So if limb spare isn't appropriate for every case, is there anything else we can do? And people have looked at stereotactic radiation therapy. Stereotactic radiation involves very, very sophisticated means of stabilising the patient consistently and delivering an extremely high dose of radiation just to the tumour and sparing the surrounding tissue by very advanced techniques.
So it's very, very clever. And these guys here, a group of surgeons and radiation oncologists set about seeing whether stereotactic radiation therapy is a good, alternative. Look at this bit I've underlined.
Complications occurred in 16 out of 17 dogs. 15 out of 17 were major complications. And in conclusions, very honestly and nobly, these guys concluded that alternative methods for limb salvage should be considered.
And this has largely been abandoned now. So, to cut to the chase, amputation is the best treatment for most appendicular cases. And there's not a very good alternative for most of these at the moment.
If you end up with a case that isn't appropriate for amputation or for limb spare. Analgesia is the most important thing you can do. You need aggressive multimodal analgesia because if these guys are not so painful right now, they can become really painful very soon.
So I would consider use of a non-steroidal, things like tramadol and gabapentin. I'd also add in osteoclast inhibitors like permidronate or zoledronnate. These stop osteoclasts from resorbing the bone.
They they act to strengthen the bone against the tumour. I might also be interested to try bedding vetMab or Librella. Now long before Librella was brought out, this paper here from 2015.
Identified nerve growth factor is a very important algesic ligand in canine osteosarcoma. So from first principles at least, I would be interested to see if an antibody that targets nerve, nerve growth factor will be an efficacious analgesic in osteosar. At the very least, I think thebrella should be reasonably well tolerated and could be combined with other things.
The other thing for a case where the tumours left in situ is palliative radiation therapy. Now palliative radiation therapy is at the other end of the spectrum to the stereotactic radiation I talked about. Palliative radiation therapy is quite an old school treatment.
It involves giving much less radiation, but often in quite high doses over about 3 or 4 doses. It doesn't really kill the cancer cells. But it is a very good way of numbing the pain receptors and reducing inflammation around the tumour.
So, as a means of cancer treatment, not so good, please don't let the owners pick up the idea that it's actually treating the osteosart, it's just treating the pain. If you do this over a quarter could get a pathologic fracture and it's usually a couple of months later. But use of zoledronnate has been shown at least in one study to reduce the incidence of pathological fracture.
And finally, I'll mention a new treatment, cementoplasty. And this company Bert Theravets. Marketing this in Europe at least, which is, a special kit which allows you to percutaneously inject cement into the osteolytic area to stabilise any fracture and hold all the bits of bone together.
I've not used this myself, so I can't comment on its efficacy. But what I can say is that the people who work for the company are very approachable and happy to discuss things with you. There's not much evidence in the published literature yet, but there was an abstract that they presented at ESONC this year.
In 12 dogs, on palliative treatment with osteosarcomas. The owner assessed pain score, decreased at 1 month in 2/3 of cases. And remained low at 2 and 6 months in half the cases.
Quality of life has improved in 80% of the dogs at one month and in 50% at 2 and 6 months. And the complications, were 3, superficial wound infection, swelling, and pathological fracture in different dogs. So we might see more of this, as the time goes on.
My key point though, if an osteosarcoma remains in situ, every effort should be made to ensure the patient remains comfortable and their welfare should be carefully monitored. Multiple oral analgesic drugs is rarely sufficient, and the best thing to consider would be radiation therapy and bisphosphonates. Let's move on to the 2nd type of treatment we need.
At diagnosis, these dogs will have micrometastatic disease disseminated, typically in the lungs and other places. So the standard of care treatment would be doxorubicin or carboplatin, chemotherapy. And with this, you will get a survival of around 12 months.
So if you think about it, that's more than doubling the survival you get with just amputation alone. So there's a clear benefit to the chemotherapy in this disease. About 25% of dogs will survive to 2 years as well.
Ideally, you want to get organised as soon as you get the osteosar diagnosis and you want to start chemotherapy 10 to 14 days after surgery. I would favour using carboplatin in the course of 6 injections. The carboplatin can cause gastrointestinal upsets that tends to be quite acute vomiting, and you can usually abrogate that to completely prevent that by giving intravenous mropotent as a pre-med.
It can also have a variable timing of severity on the bone marrow 10 to 14 days later. So, some dogs get very myelosuppressed, others not. Some dogs are maximally myelosuppressed at 10 days, other dogs maximally myelosuppressed, you know, at 14 or 18 days.
So it can be a bit variable. But in general, it's well tolerated. You don't have much of a problem with it.
Doxorubicin is an alternative, equally good treatment for an osteosarcoma. Now, doxorubicin is famously cardiotoxic, but let me tell you, I've rarely seen that as a clinical phenomenon. I think that's overstated.
What is understated about doxorubicin is its ability to cause diarrhoea and vomiting, and this can be severe. As in, you need to admit the dog and put him or her on fluids and intravenous injections to be able to treat and support the dog through the diarrhoea episode. So you need to be very careful with this, and I think doxorubicin is something, that can limit a dog's welfare for a few days if you give diarrhoea.
So that's why I'd go with carbo. It's been shown to be equally good but no more than the doo. And when people have looked at an alternating carbo doxo protocol, there's no benefit either.
So each, each of these things are equally good. No, it's a bit perverse, isn't it? The the chemotherapy clearly has a benefit.
It at least doubles the survival time of the dog after amputation. But we worked hard, we give the course of 5 or 6 injections. And then we're in the habit of just stopping.
I'm waiting for the disease to recur because it will recur, you know, and we, that's, that's beyond contention now. We're not going to win this battle. So it seems perverse that we just throw in the towel after these injections and people have wondered, is there anything we could be doing to kind of maintain the pressure on the cancer and hold it at bay and delay its recurrence.
And one easy thing people looked at is using metronomic chemotherapy to maintain them after limb amputation and carboplastic. And you can see in the survival curves that they are a little bit different. One group of dogs just had their carboplatin, one group of dogs had carboplatin and metronomic chemotherapy, but ultimately there's no significant benefit between the two groups.
There's a lot of interest in using TKI drugs like Cereno. But again, even less difference between the two groups, no significant benefit. And here, people use adjuvant erullius after standard of care carboplatin chemotherapy.
And no significant benefit either. So The jury is still out as to the benefit of maintenance therapy, but it does seem like a good idea. And there are now some very interesting clinical trials which are often widely discussed on forums between dog owners and dog breeders, and particularly referring to dog breeds that have a high rate of osteosarcomas.
This is one very, very interesting trial here, where they did amputation, they did carboplatin chemotherapy, and then as a kind of further treatment, they looked at immunotherapy. With a, a vaccine product based on Listeria. It's an altered Listeria as a vector, to give you HER2 specific immunity, OK?
So in this group of 18 dogs, you showed that they had an immune response. And very excitingly. In the group that had the chemotherapy and the vaccine.
The average survival was 2.5 years. 78% were alive at 1 year, 67 were alive at 2 years, and 56 were alive at 3 years.
And if you look at the survival curves here, You find a group that had carboplatin in the vaccine if they're much, much better than those that just have the carboplatin on their own. So finally it looks like something is having an effect here. But then there's a few spammers in the works.
We're using Listeria as a vector. And it looks like a clinical case of Listeriosis. And we go on further.
In a survey of the safety of the vaccine, a group of 49 dogs here, 60% of the dogs experience an adverse effects, nausea, lethargy, fever is most common following the vaccine, and very concerningly, 8% cultured positive for Listeria. These are things like amputation site abscesses, septic stifle joint, bacterial cystitis, or a positive lung culture at PM. Postmortem 24 hours after the vaccine.
So With this vaccine, it sounds very exciting, but actually these adverse effects are not very acceptable for our dogs, and what could be even worse is that if you have a dog who's got clinical listeriosis, he or she is a health risk to their family. So this exciting study, as far as I'm aware, has now been abandoned. Currently, the standard of care, the best we can do.
Would be 4 to 6 injections of carboplatin or doxorubicin starting 14 days after surgery. This isn't where I want to leave things though, because the key to getting the best outcome in osteosarcoma. Is to monitor We often don't do that, do we, in veterinary medicine.
We give the treatment and then think it's worked. But we need to restage whether there's clinical signs or not, typically every few months if you can. And we want to start intervening when we get to this stage, when we've got just one lung tumour here.
Dog's absolutely fine. This tumour has been detected incidentally on staging. What we call this is oligo metastatic.
As opposed to fulminantly metastatic. So when you get this oligometastatic state, now is your time to intervene and start with something different. Once the mets are formed in the lungs.
You're not going to get rid of them. Very unlikely to. So what your treatment is designed to stabilise or retard the developments.
So when you're at the oligometastatic stage, I would encourage you to employ the resist criteria. That is response evaluation criteria in solid tumours. It's used to monitor the efficacy of treatment objectively.
You identify 2 to 5 target lesions. You, calculate the maximum diameter and you add these together to get one number. OK.
And then on your next imaging. You look at these lesions again, get your 2nd number. And if the number is great and 20% bigger, we'll call it progressive disease.
If it's greater than 30% less, we'll call it a response. OK. Partial response is where the mass has shrunk, but it's still visible.
Complete response is where it's gone. And if you've got a change in size between these numbers, we'll call it stable disease. So you outline your resist measurements, and then as a second line therapy, I'd encourage you to use the chemo drug that you haven't used already.
Alternatively, you could use metronomic chemotherapy. Metronomic chemotherapy is a treatment that doesn't really target the cancer cells, it just makes the environment of the tumour hostile to the cancer's growth. So in theory, at least, it shouldn't matter so much what cancer you're actually treating.
And with the addition of thalidomide, a very potent anti-angiogenic agent, metronomic chemotherapy has been shown to be a very, reasonable treatment, at least in other metastatic diseases like hemangiosarcoma. You could potentially consider single agent thalidomide. But if you're not gonna use other anti-cancer drugs, I would encourage you to use NSAIDs because pulmonary mets can cause a lot of inflammation in the lungs, and this can be painful and it can affect breathing.
I'll briefly show you another very recent study here. Where they used the serreib ladia. Along with a high dose of losartan, and losartan is, is not used much in veterinary, but it's an angiotensin to antagonists, you know, similar to telmisartan or Saintra.
Now very excitingly in this study, they said that 50% of dogs with metastatic osteosarcoma benefited. OK. They also said the adverse effects for grade 1 or 2, and for you or me, that means mild things that you can almost discount and don't need any treatment, like mild weakness, mild hyperexia, mild diarrhoea.
No hypotension was observed. When you look at the data, You find that in this group of about 22, 23 dogs, it's only these 4 had significant shrinkage of the tumour. But there were another 5 dogs denoted by the asterisk, sorry, 7 dogs, isn't it?
Where the disease remains stable. So remember, it's got to be less than 30%, the original size to call it a response. So that's quite interesting.
When you look at the survival between the groups, the groups that had the high dose losartan as well as the serinib, have had an average survival of about 5 months, whereas the group that had the taserinib only lived for 3 months. So you're talking for kind of 2 months difference here and if you look at the P value, you'll find it's not quite significant. So it's interesting.
But it's not something that has changed the game. I'd also be very careful about using drugs like losartan or licence, and also because the dose they had to use to get this improvement in this study is 10 times the blood pressure management dose and you just don't know what that's going to do to some dogs. So ultimately you get to the state of fulminant metastasis like this cool dog in the radiograph on the left.
Now when a dog has a large cancer burden like this, they tend to feel poorly malaise, fever, lethargy, weight loss, cachexia, etc. And this is due to the inflammation or the cytokine release from a large cancer burden. Now in this case, I hope they've been on non-steroidals already and non-steroidals aren't cutting it.
You could very carefully consider stopping the non-steroidals, allowing a washout period of a few days and starting steroids. Now, don't jump to this. Steroids will undermine the anti-cancer immune response.
For anything other than lymphoma, I'd be very careful about using steroids because I think they can do more harm than good. But in the situation of disseminated mets and conventional anti-inflammatories like non-steroidals aren't doing the job, steroids can provide some respite and in a lot of cases, they make the dogs feel significantly better, albeit for a short period of time. Remember things like analgesia because these lung tumours can hurt with phosphonates and things.
Appetite support. You might want to consider omega 3 supplementation if they're losing muscle mass. You might want to consider bronchodilators.
Mainly the phosphodiesterase inhibitors like theophylline, melofile and things like that because they help to clear some of the flu fluid from the lungs. And you might want to consider antibiotics if you think there's a component of secondary infection. The serranib or palladia on its own has long been shown to have a very mild effect in stabilising the growth of these metastatic lesions too.
One sequel you may get is this. What's going on there? The the dog, the dog's hock below the hock, the legs much thicker than above the hock.
Can you see this one? Suddenly the front leg has become very, very thick and so the back legs have as well. And this is hypertrophic osteomyopathy, osteopathy, sorry, hypertrophic osteopathy.
It's where you get this periosteal reaction. All the way up the limb. And it's believed to be due to a balance of vagal vagal stimulation to the leg.
It's actually quite poorly understood. But metastatic osteosarcoma is an important cause of this. It can also occur due to things like heartworm as well.
It doesn't have to be due to a cancer. Typically, it starts distally with swelling of the leg distally and moves proximally, and these dogs can often be quite sore, they may have a fever as well. Treatments to consider, there's no great treatments, I'm afraid it's just supportive.
You might want to use bisphosphonates or anti-inflammatory drugs, possibly steroids. You might want to consider Pelladia again for the reasons I've just discussed in a metastatic osteosarc. But sadly, there's nothing we can do to reverse this state really.
But the key to getting the best outcome you can for your osteosarcoma cases is monitoring, re-staging, and adapting based on disease progression and also the clinical signs and modulating your supportive care. Ultimately, for a non-metastatic appendicular osteosarcoma, if you just do amputation, they'll live for about 3 to 5 months before metastatic disease is limiting their life. Similar if you just do palliative radiation.
And if you do palliative radiation and you give chemotherapy, it's still the same. Because remember the legs in situ and the palliative radiation will be a temporary fix. It will just make the leg bearable for a while and then the effect will wear off or you get a pathologic fracture and the animals are still put to sleep.
So if you're not going to do amputation, you're just doing some palliative treatment, there is, you might want to consider what benefit chemotherapy is going to give. Some would say it would not be. It's not gonna change the game.
However, if you do limb amputation to take the local disease out of the picture and you give chemotherapy, average survival 10 to 14 months, and a quarter of these live for 2 years. If it's metastatic at diagnosis, average survival is about 3 months, sadly, 3 or 4 months. One study says with surgery alone, just 3 days, but I think that was probably biassed by the population in that study.
And surgery and chemotherapy alone again, about 2 months, 2 to 3 months. So you're not gonna get more than a few months if there's prominent metastasis at diagnosis as visible on a radiograph. Other locations can be important.
Because as we said, the disease is very similar, but runs at very differing speeds depending on where you are in the body. So osteosarcomas of the head tend to have a lower metastatic rate. OK, 37% is reported.
We used to think it was lower, but now we know how to treat these tumours properly and get complete excision if we can, we find that the greater number developments later. Maxillectomy has been associated with the poorer survival of mandibullectomy, and that's probably not due to features of the tumour, but just due to the difficulty in, controlling disease in the maxilla versus that in the mandible. And actually in rare cases of orbital osteosarcomas, prolonged survival has been seen with surgery alone.
If you've got an osteosarc distal to carpal tarsal, and with surgery alone, you've got an average survival of 15 months. Now, my personal choice, if we get one of these slower or less aggressive type of osteosarts of the head, distal to the carp and tarsus, I would still offer chemo. I think the metastatic rate, even if it is 37%.
It's still a bit too high for my liking, and I want to do everything I can to try to neutralise these micro metastases. I haven't got a lot of evidence from clinical trials of that, but that makes sense to me. Got some more aggressive locations though like ribs, average survival 3 months or 8 months, scapula 7 months with surgery and chemo.
Remember these scapular ones, you could often do a partial scapulectomy. So it may be limb sparing, but it's still a more aggressive disease. Verteal ones a few months and these extra skeletal ones is typically again several months.
Some clinical findings can be prognostic like ALP, if it's greater than the upper limit of the reference range, it's associated with a shorter survival. The monocyte and lymphocyte counts with a high monocyte count and low lymphocytes before treatment is associated with shorter disease-free interval. Higher grade tumours are associated with a poorer prognosis.
Most of the osteosarcs we see are higher grade though. And then you've got the histological subtype osteoblastic, chondroblastic, etc. Hasn't been shown to have a clear impact on outcome yet.
There is a suggestion that the osteoblastic minimally productive subtype has been associated with a higher number of high grade cases though. And the older or the middle aged dogs tend to have better survival than the young ones, or rather that the young ones and the very old tend to do the poorest. And last but not least, we'll just mention cats.
Cats get appendicular and axial osteosarcomas, just like dogs. When it's appendicular, the femur and the proxyal tibia are the most common. Axial skeletons, roughly half, the proportion of those, appendicular skull and pelvis are most common.
However, interestingly, extra skeletal osteosarcomas comprise up to 40% of these in cats, and they often come up as injection site sarcomas or sarcomas in the mouth, mammary area, or intestines. But the appendicular osteosarcoma is actually a low metastatic rate, 5 to 10%. Adjuvant chemotherapy is not indicated.
And with amputation alone in the appendicular skeleton, you've got a survival time of 2 to 4 years. And the axial skeleton though is much shorter, 6 to 7 months. In summary then, many differential diagnoses for an aggressive bone lesion are available.
Please bear in mind that they have different treatments. Use signalment and anatomic location to refine these differentials, and fine needle aspiration will give you the diagnosis in most cases. Remember that osteosarcoma requires local therapy for pain control and medical therapy to control the metastatic disease, two separate problems.
For local therapy, amputation remains the mainstay. Limb spare is inappropriate for many cases due to advanced disease or inappropriate anatomic location. A dog with a typical distal radial osteosarcoma can expect to survive 10 to 14 months with surgery and chemotherapy.
Carboplatin and doxorubicin are the most effective chemotherapy agents. The benefit of maintenance therapy when the course is finished has not yet been proven. But the benefit of frequent re-staging and adapting your treatment to the patient is clear.
Consider multimodal analgesia, radiation therapy, and bisphosphonates for palliative cases. Remember that osteosarcoma lesions in cats can look deceptively non-aggressive. An osteosarin cats has fewer differentials and is less metastatic.
The benefit of chemo has not been shown. If you're interested in learning more, I'd encourage you to, look at Withrow McEwan's, small animal clinical Oncology. This is the Bible, the clinical oncology.
And for some of the, some of the diagnostics, you might want to look at the new edition of the rule here, which is a very well-written chapter on aggressive bone lesions. Might also want to follow veterinary cytology and ESON on Facebook. And finally, I'd like to say thank you to everyone who works with me every day at Highcroft Referrals.
I'd like to say a very big thank you to Webinar vets for asking me back to speak again. It's always a pleasure to speak for Webinar vet. And ultimately, I'd like to say thank you to you guys for tuning in to listen on a Thursday evening.
If you've got any questions, I will do my very best to answer them right now. I'll just check the Q and Q and A box. Can't see anyone has put anything there.
Oh, something's come up. Oh, thank you. Thank you, Martin.
That means a lot. Martin said thank you for the great lecture. I'll just give you guys another.
I don't know, 10 seconds or so. Great, well, looks like no questions at the moment. If you do have anything that comes up, you're more than welcome to drop me an email.
So thank you again for everyone for tuning in and thank you ever so much for Webinar vet for asking me to speak. Stay safe and I hope to see you guys again soon. Bye now.