OSA

Question 1

What is the most common vertebral neoplasia in dog?

Answer 1

OSA

Question 2

What was the MST of dog treated with surgery alone, surgery+ chemo, surgrey + RT, surgery+RT+chemo?
Is a combinational therapy benefitial?
(Dixon, VCO, 2019)

Answer 2

Surgery: 42 D
Surgery+ Chemo: 82 D
Surgery + RT: 101 D
Surgery+ RT+ Chemo: 261 D

Radiation therapy possibly with chemo significantly improves the survival of dogs treated with palliative decompressive surgery.

In humans gold standard en bloc vertebrectomy with wide tumor margins + RT and/or chemotherapy

Question 3

What was the reason for euthanasia in dogs with vertebral OSA treated with surgery/multimodal therapy?
What prognostic factor corcerning survival has been suggested previously?
(Dixon. VCO, 2019)

Answer 3

Local progressive disease.
Metastatic rate 14%
Neurologic function–> decompressive surgery may improve pain and neurological status, 89% stabilized or had improvement following surgery (vs. radiation therapy alone)

Question 4

What was the MST of dogs presenting with and without (just pain) neurological symptoms treatad with surgery for decompressive vertebral OSA?
Dernell, JAAHA, 2000

Answer 4

MST without 330 D

MST with 135 D

Question 5

In one recent study was periostin upregulated in canine OSA? Was the upregulation correlated with time to metastasis?
What other significant finding was demonstrated in this study?
(Alfino, Vet pathol, 2021)

Answer 5

Yes, periostin was significantly upregulated in canine OSA.
It was correlated with time to metastasis (although small sample size).
In periostin high tumors enhancement of protumoregenic pathways was seen: WNT-signalin, EMT (periostin important for TGF-beta expression) and angiogenesis.
In periostin low tumors upregulation of INF-alpha and INF-gamma genes (antitimor activity)

Anti-periostin Abs can be used to detect periostin in OSA tumors, which is correlated with WNT- pathway enhancement and could be used for possible anti-WNT drug research.

Question 6

What are C-cirles and is C-circle assay suitable for the detection of alternative lengthening of telomers in canine OSA?
Was c-cirle assay positivity associated with shorter survival?
(Bicanova, VCO, 2020)

Answer 6

C-cirles are extrachromosomal circles of telomeric DNA that are specific for alternative lengthening of telomers (ALT).
This recent study showed that it is suitable for the detection of ALT activity in dogs.
It was associated with shorter survival and was significant in the Cox model.
More positive dogs were male and Rottweilers seemed overrepresented.

Question 7

Is whole lung irradiation feasable and safe in dogs with appendicular OSA?
Did it have an impact on disease free interval?
(Brehm, VCO, 2021)

Answer 7

Whole lung irradiation is feasable, no signs of pneumonitis or fibrosis occured.
There was no sig. impact on DFI of irradiated dogs.
10x 1,75 Gy

Question 8

Was the expression of exportin-1 (XPO1) demonstarted on OSA cell lines, tumor cells or osteoblasts?
What happens if OSA cell lines are treated with Verdinextor (an inhibitor of nuclear export molecule)?
With wich drug was a synergetic effect demonstrated?
(Breitbach, VCO, 2021)

Answer 8

The expression of exportin-1 (XPO1) was demonstrated on OSA cell lines and a subset of OSA tumors.
If treated with verdinexdor a dose-dependent growth inhibition and increased casp 3,7 activity was seen (already with low cc).
The combination of DOX and verdinexdor demonstarted synergism in 3 OSA cell lines.

It could be a potentally new strategy of OSA treatment.

Question 9

In a recent study how was the administration of zoledronic acid tolerated? Which adverse events occured?
Which are the bone turnover markers that can be used to monitor the effectivess of aminobisphosphonates?
(Brewer, VCO, 2021)

Answer 9

Zoledronic acid was tolerated well.
Adverse events were: azotemia, vomiting, panceatitis, cutaneous ulceration, diarrhea.
Azotemia could not be correlated with increasing total dose recieved. (all dogs were recieving NSAIDs concurrently).
The bone turnover marker are: bone specific ALP, urine N-telopeptide

Question 10

What are the 3 histologic types of surface OSAs?
What is the prognosis and metastatic rate for these dogs?
(Cook, VCO, 2021)

Answer 10

parosteal (outer fibrous layer of the periosteum), periosteal (undifferentiated mesenchymal cells of the deeper periosteum) and high-grade surface OSA

The median PFI 15 months, MST 19 M (1,5 years). (for parosteal MST could not be calculated)
Mets occured in 6/11 dogs (higher then expected)
No factors were sig. associated with survival.

Question 11

Is 18F-FDG PET/CT effective at diagnosing metastastatic and comorbid lesions in canine OSA?
How does it compare to whole body CT or scintigraphy?
What was an important limitation in this study?
(Crooks, VRU, 2020)

Answer 11

Yes, 18F-FDG PET/CT identified mets in 24% of cases and 16% of comorbid lesions.
The mets were seen in the lungs (7%), bone (10%), 5% (RLN), 1,5% (extraskeletal or abdominal)
It is better at identifying metastasis: scintigraphy (8% bone), whole body CT (5% lungs, 0% bone).

Not all lesions were comfirmed by cyto or histo. But in the other studies this was the same limitation.

Question 12

A recent study assessed the promoter methylation of PDGFRbeta in canine OSA.
What was the conclusion of that study?
(Gentilini, VCO, 2020)

Answer 12

The promoter of PDGFRbeta was constantly demethylated, however it did not correlate with its expression. This could confirm the hypothesis that posttranscriptional regulatory elements may act on OSA (micro-RNA).

Question 13

What may be contributing to platinum resistance in OSA?
How can this be tackled?
(Inkol, VCO, 2020)

Answer 13

There are special copper transporters (Atox1), which have the ability to aggregate platinum agents, preventing them from forming DNA adducts.
Small molecule inhibitor, DC_AC50 synergised with Carbo the reduce cancer viability, mitotic activity, apoptosis and migration.
This can be an aid reducing or preventing aquired Chemo resistance.

Question 14

Can benign bone infarcts be differentiated from malignant ones by radiographoc changes?
(Jones, JAVMA,2021)

Answer 14

No

Question 15

According to a recent study when should post-operative chmotherapy be initiated in canine appendicular OSA?
(Marconato, JAVMA, 2021)

Answer 15

It should be initiated <5 days after surgery.
The median TTP was 1 year (375 days) and MST 16 months (445 dasy), which was significantly longer than the dogs recieving chemo after 5 days.

Question 16

What is in the Goldie and Coldman mathematical model described?

Answer 16

It is stated that the drug sensitivity of neoplastic cells is related to their rate of spontaneous mutation toward a drug-resistant phenotype. Because tumor mutation increases with time, a longer interval between surgery and chemotherapy may increase the occurance of a chemoresistant phenothype.

Question 17

What is in the mathematical model of Harless and Qui indicated?

Answer 17

It is indicated that the effectiveness of chemotherapy is inversly proportinal to the tumor burden requaring erradication (this is a function of the interval between surgery and chemotherapy).

Question 18

In a recent article evaluating SRBT in canine appendicular OSA as a form of limb-sparing what were the outcomes of the study considering pain control, tumor necrosis, time to progression, MST and pathologic fracture?
What was the recommendation?
(Martin, VCO, 2020)

Answer 18

Pain control was high, 84% had an improvment at a median of 3 weeks up to median of 6 months.
Tumor necrosis was >80% in 50% of the patients (80% is considered needed for local control).
TTP 5 months (143 days), MST 8months (233 days).
More then 1/3 had pathologic fractures (41%).
Tumor location was associated with survival. GTV and PTV were inversely associated with survival.
Metastatic disease at the time of treatment did not influence survival.
Amputation after pathologic fracture lead to longer survival than without amputation.

More careful patient selection is needed (less tumor necrosis, enough skin thickness).

Question 19

What potential side effects can occur after lyophilized formulation of live, attenuated Listeria vector vaccine?
(Musser, VCO, 2020)

Answer 19

Mild lethargy, nausea and fever.
However, 4 dogs (8%) had positive culture up to 30 days (amputation site abscess, stife joint infection, bact. cystitis, pulmonary abscess of a metastatic lesion).

Unclear if lyophilization had an effect, in the previous trial the vaccines were cryopreserved.

attenuated Listera was used as a vector to express a human chimeric HER+ fusion protein

Question 20

Is higher dose + chemotherapy better conventional hypofractionated protocol+ chemo in canine appendicular OSA?
What is the infuence of pain at presentation?
(Nolan, VCO, 2020)

Answer 20

Higher dose (3x 12=36 Gy) combined with chemo leads to sig. longer MST (1y vs. 5months).
Overall survival times were better if the basline scores of pain were low (RT+Chemo). There was no diff. without chemo.

Question 21

What was the outcome of dogs with OSA treated with limb-salvage after secondary amputation?
What were the factors which positively influenced survival?
(Wustefeld-Janssens, VCO, 2019)

Answer 21

Dogs that had secondary amputation lived signifincantly longer (604 days vs 385 days).
Survival was influenced positively by amputation, moderate (infection responded to treatment but either did not resolve or indefinate AB treatment was undertaken), severe (not responding to AB, multiresistant, permanent imparmaint of function) surgical site infection and age.

Question 22

Is the usage of SC carbo in dogs with appendicular OSA underging amputation advisable?
(Santamaria, JAVMA, 2019)

Answer 22

No, GI adverse events were high and no survival benefit was noted in comparison with IV carbo.

Question 23

Is the administration of toceranib alone or in combination with other chemotherapeutic agents advisable in dogs with OSA according to OSA cell line and xenograft models?
(Sanches-Cespedes, VCO, 2019)

Answer 23

No.

Question 24

In the tumor microenviornment from OSA, the inceased presence of which cells could play an important role?
(Withers, VCO, 2018)

Answer 24

Higher amount CD204+ macrophages (these are actually M2) led to an increased DFI
In proximal humerus lower amount of CD204+ macrophages and lower ST.

Tumor promoting M2: IL-4, IL-13 (Th2), IL-10, TGF-beta
Anti-tumor M1 activated by: LPS, TNF-alpha, INF-gamma

But maybe the role of M2 are different in OSA.

Question 25

Do dogs with digit, metatarsal and metacarpal bones have a longer DFI and MST?
Are there any relevant prognostic factors?
(Tremolada, VCO, 2020)

Answer 25

Yes, these dogs lived longer. DFI 1 year, MST 687 (almost 2 years)

Prognostic factors could not be indentified.
The role of postop chemo was unclear due to small sample size (15 dogs), although 48% developed metastasis.

Question 26

What is the prognosis of dogs with OSA with cutaneous or subcutaneous metastasis?
Which sites do they occur and what could be benefitial?
(Parachini-Winter, JVIM, 2019)

Answer 26

The prognosis is grave (11 days), can be better with surgery+chemo (3 months) or chemo alone (2 months).
Can be the 1 metastatic site, before the lung.
Trunk and ventrum most often.

Question 27

Can TPO cause the OSA in dogs?

Selmic, JAVMA, 2018

Answer 27

Yes, dogs with TPO are 40 times more likely to get OSA and the risk increases 11% with every 1 kg weight.
OSA is an important differential in dogs with worsening lameness after > 1 year of TPO.

Question 28

According to a recent study what is the metastatic rate in cats for appendicular OSA and is OSA of the humerus more aggresive in cats as well?
(Nakano, JAVMA, 2021)

Answer 28

The metastatic rate is higher then previously reported, 46% .Scapular OSA number was higher.
OSA of the humerus seems to be more prone to mets, 6/7 cats developed metastasis.
MST was also shorter then previously reported, 530 days.