Osteosarcoma and amputation and survival time

RE: Osteosarcoma and amputation and survival time

Beats — Tue, 03 Jan 2023 22:14:18 GMT

Thanks Gerry, once again, for all that info and wisdom!

Like Michael, I seem to be seeing less "classical" OSA cases than I did 15 years ago - I had put this down mainly to seeing less Rottweilers (and a general shift to smaller dogs). Indeed, when I started going through cases, I found most I'd seen in the last 10 years were not what I think of as "classical" OSA at all. An amputated toe claimed to be "osteosarcoma" by the lab and still alive and well 7 years later; one described as possible "telangiectic" osteosarcoma (whatever that may be) and still alive to tell the tale; A cat with "bone surface osteosarcoma" going strong 8 years later etc. I think that is what has skewed my perception - I don't remember any Rottweilers doing especially well (although to be fair that may be a self-fulfilling prophecy as I suspect I euthanased most of them on presentation).

Here is a link to "MIMIC" in case of further interest: https://www.ethosdiscovery.org/clinical-study/minimally-invasive-metastasectomy-in-canines-mimic/ by Chris Thomson (https://vshnc.ethosvet.com/about-us/our-team/bio/?bio-id=16134). I think it is just thoracoscopic metastectomy.

RE: Osteosarcoma and amputation and survival time

Michael Woodhouse — Sun, 01 Jan 2023 00:41:31 GMT

[quote userid="16672" url="~/001/veterinary-clinical/small-animal/oncology/f/discussions/30523/osteosarcoma-and-amputation-and-survival-time/240346#240346"]jinxed yourself Michael![/quote]

Thanks, and Happy New Year!

RE: Osteosarcoma and amputation and survival time

Martin Hamilton — Sun, 01 Jan 2023 00:39:10 GMT

Not an osteosarc, but we've now had two oral malignant melanoma cases that were referred for staging and excision with margins via mandibulectomy or maxillectomy that had metastasis. One of them had thoracic mets evident on CT but not on the radiographs taken by the referring vet, and ultimately the owner elected to pursue palliative care rather than surgical excision.

[quote userid="3169" url="~/001/veterinary-clinical/small-animal/oncology/f/discussions/30523/osteosarcoma-and-amputation-and-survival-time/240345#240345"]About to jinx myself, but are people seeing as many osteosarcomas as in the past? In my first few years of practice we would find 1 or 2 per year and despite the small animal work growing significantly - I don't remember one in the last 10 years.[/quote]

Coming from a private referral across the pond, osteosarcs are alive and well. In GP back home I saw a few, one presenting with a pathologic fracture, I remember one in GP here in Canada, and now in referral I have seen 3 oral osteosarcs in the last 12 months. Definitely jinxed yourself Michael!

RE: Osteosarcoma and amputation and survival time

Michael Woodhouse — Sun, 01 Jan 2023 00:35:23 GMT

About to jinx myself, but are people seeing as many osteosarcomas as in the past? In my first few years of practice we would find 1 or 2 per year and despite the small animal work growing significantly - I don't remember one in the last 10 years.

RE: Osteosarcoma and amputation and survival time

Rob Loxley — Fri, 30 Dec 2022 18:52:03 GMT

I've always wondered for diseases where presence or not of metastasis may markedly change treatment offered, whether the imaging modality impacts outcome. eg. if mets check done on a ct which is more sensitive, may the patients be treated differently than if staged with xrays, and thus the outcomes altered?

RE: Osteosarcoma and amputation and survival time

Gerry Polton — Fri, 30 Dec 2022 09:52:51 GMT

My vague answer to the 4.5 month thing is that when I do see a patient that has amputation only, I predict 4.5 months life expectancy and I derive an uncomfortably macabre satisfaction if I am right. This happens with sufficient regularity that I still predict 4.5 months. There are very few cancer contexts where I would predict with such precision and I suppose, honestly, this has become a little bit of a game for me. Of course I do see cases which surprise me. Thankfully, in an unexpected twist, one such case belonged to a colleague, turning all accepted beliefs about veterinary-owned patients having a poorer prognosis completely on their head!!

In relation to histotripsy, yes!! I love this concept. As it happens, there are two centres in the Western world that are working on this technology in veterinary cancer more broadly, Virginia Tech and The Royal Marsden a little closer to home. We have an affiliation with the Marsden and have been advising on their development of this technology. We are midway through a study to use the same approach in bladder tumours. Watch this space (patiently...)

I have not come across MIMIC and unfortunately, when I try to look it up I find too many references to the word, mimicry, to find something relevant. In principle, I struggle to see value in thoracoscopic metastectomy unless we are talking about removal of solitary or perhaps a couple of slow-growing lesions that have persisted sufficiently long after amputation and chemo that their removal can be justified (~10+ months). We currently talk about doing that by thoracotomy so thoracoscopy would be less traumatic and therefore easier to justify so long as it achieved the same levels of perioperative safety.

Cementoplasty I don't think will work. If you could assure that the cement filled the space in a structured manner it could be a nice palliative measure. There would be some thermal damage to the tumour and you would achieve a stiffening of the diseased bone. In practice, the cement cannot be distributed evenly: there is tissue present which doesn't want to simply move out of the way; the tumour has eroded bone so there are lots of small holes in the cortex that the cement will leak out of (as well as the hole you are injecting it through); the tumour is not confined to the medulla, it infiltrates into and through the cortex into the soft tissues, and the leaking cement induces unpleasant inflammatory reactions. You could achieve a better bone stiffening benefit by plating the bone or using an external fixator.

All great questions.

Happy New Year, everyone

Gerry

RE: Osteosarcoma and amputation and survival time

Beats — Thu, 29 Dec 2022 18:17:46 GMT

Thank you Gerry for that incredibly comprehensive, contemporary commentary on the state of osteosarcoma! Can I take this opportunity to say that I love your work and, having read a number of things you have written over the years am very happy in the absence of double-blinded placebo controlled trials to take the second best of "What Gerry said!" You were the first person whom i read suggesting that what the mast cell tumour looked like (size, nastiness etc) may be useful information to take into account in decision making and I have found that in particular most useful over the years.

Regarding the 4.5 months median survival with amputation alone, is the reason that this is accepted and not questioned because it fits with the experience of yourself and others that see many more cases of osteosarcoma receiving amputation alone than I do? My instinct would be that this is likely the case, but a small part in my brain needs satisfied that yourself and/or others do indeed see sufficient cases that get amputation alone to notice if the median survival with amputation alone was indeed longer than 4.5 months as I wonder if the cases you see usually get more treatment than amputation alone and thus amputation alone cases may make up a small proportion of the large number of osteosarcoma cases you see?

I have checked briefly at the cases I have seen in last decade and concluded that I haven't seen enough that got amputation alone to be able to make any objective observations on the median survival time. Interestingly the longest surviving case I remember declined amputation.

i had been googling to try to answer my question and came across a few experimental treatments I hadn't heard of before. Can I ask if you have an opinion yet on histotripsy, MIMIC (thorascopic removal of lung mets I think?), or cementoplasty?

I see that there was recent data from a large study that looked at likely breeds in the UK (Dog breeds and body conformations with predisposition to osteosarcoma in the UK: a case-control study - PubMed (nih.gov)), and perhaps that same data of 1756 dogs with osteosarcoma will be mined for other interesting facts like contemporary MST from amputation alone in the near future, satisfying my curiosity still further.

RE: Osteosarcoma and amputation and survival time

Gerry Polton — Thu, 29 Dec 2022 09:20:40 GMT

Good morning

I don't believe there is a paper which compares outcomes in the side by side manner you are looking for. The data from the 70's and 80's were highly reproducible and therefore haven't been challenged. We accept, perhaps blindly, that 4.5 months is the median survival time with amputation alone. We choose to accept the results of Phil Bergman's group, J Vet Intern Med 1996 Mar-Apr;10(2):76-81, which yielded an 11 month median survival time with amputation and carboplatin. There are definitely factors that influence outcome and these are represented to varying degrees in the multiple retrospective studies that are out there. Consistently, proximal humeral location has a poorer prognosis, mandibular location has a better prognosis. These are reproducible findings as though these are slightly different disease processes. There are some less reproducible but nonetheless interesting findings: Rottweilers tend to do less well. But one can speculate about the countless scientifically plausible reasons why this might be: patient demeanour, cost of treatment/owner demographic, disease more advanced at time of diagnosis, concurrent cancer predisposition, etc. Intriguingly, there is some evidence that Rottweilers carry a specific genetic predisposition to osteosarcoma. It is also true that Rottweilers are most likely to develop osteosarcoma in the proximal humerus. For balance, I have treated a number of Rottweilers and a good number have enjoyed normal outcomes.

Anyway, I didn't mean to turn this into a Rottweiler monograph. The point I am making is that there are certain things that we, as a community, accept as unshakeable truths and the osteosarcoma MST with amputation alone or with amputation plus chemo are on that list. There are definitely changes in pet ownership habits and in dog genetics over time so it is always good to challenge long-held views, so I support the question. If it comes from an observation that a couple of recent cases have fared better than expected, that's normal. 50% of cases will always do better than the median. The exemplar study of amputation alone revealed that 11% of dogs were alive after 12 months and 2% after 2 years. There has always been the thought that amputation might somehow promote metastasis progression, as though the primary tumour somehow puts the brakes on development of secondary metastases. Check out this paper if you want to fuel that particular thought process: J Am Vet Med Assoc. 2006 Jun 15;228(12):1905-8.

The current area for development in osteosarcoma is in the application of immunotherapy. We are seeing some interesting results but not across the board. There's definitely something happening but we don't have the tools yet to identify who is going to benefit from it and who isn't, or indeed how to optimise benefit.

Anyway, great chat. Thanks for starting it off, Beats.

Gerry

RE: Osteosarcoma and amputation and survival time

Martin Hamilton — Thu, 29 Dec 2022 05:23:05 GMT

I know they're a cohort from some time ago, but as far as my paper library is concerned that's the best you'll find with that kind of sample size. However, I mostly have access to dental journals and Journal of Veterinary Surgery, so there may be something out there I dont have access to.

I think you'll struggle to find a paper with a control group vs a group receiving carboplatin - due to the nature of our industry and a lack of foresight and finances most papers are retrospective in nature. Hope someone can help you find something more recent or a little more thorough!

RE: Osteosarcoma and amputation and survival time

Beats — Wed, 28 Dec 2022 09:12:01 GMT

Thanks Martin!

Those 65 cases are from 1996-2006.

My issue is that there is not a contemporary control group receiving amputation without carboplatin, so it's difficult to attribute any meaningful survival benefit to the carboplatin.

RE: Osteosarcoma and amputation and survival time

Martin Hamilton — Wed, 28 Dec 2022 02:29:25 GMT

Hi Beats,

This is out of my wheelhouse (coming from the dentistry side of things), but during my reading for maxillofacial OSA in anticipation of boards I found this semi-recent reference that may be of use.

https://avmajournals.avma.org/view/journals/javma/238/2/javma.238.2.195.xml

65 dogs, seems like they had a median survival time of 277 days, used carboplatin at a dose of either 250-300mg/m2 for treatments, with a median number of 4 treatments/dog, but dose used was not signifciantly associated with outcome. It's a 2011 paper, so there may be some newer stuff out there. If you want more info, feel free to send a PM.

Hopefully someone with more knowledge on the existing literature or some experience with a multitude of these cases can give you an answer.