Bachata Rosa Flashcards
Mutation and overexpression of what gene is present in both human and canine LSA?
What other TSG was also recently evaluated and found to be abnormal in both human and canine B-LSA?
p53 - lower remission rate and ST
Mutated in 16% and overexpressed in 22% of dogs with high-grade LSA
Hypermethylation of DAPK CpG islands - 45% of B-cell LSA; negative PI for survival in both humans and dogs
DAPK involved in IFN-y mediated apoptosis
What is the most common immunophenotype and cytomorphologic sub-classification of LSA in Boxers?
85% T-cell lymphoma
TCR ab+, CD4+
Lymphoblastic high-grade
What is the MST of Boxers and Boxer mix breeds when treated with the LOPP chemotherapy protocol? Prognostic indicators found?
MST - 3m (99d)
Boxers 6x more likely to develop PD
Boxer breed = negative PI for PFI
What is Ritcher’s syndrome and the MST* in dogs?
CLL -> lymphoma
Characterized by the presence of pleomorphic immunoblasts
Poor tx response and prognosis
MST 41d
What are the identified prognostic factors in dogs with CD21+ LSA (2)?
Large cell size = shorter remission duration and ST (HR: 2.77x more likely to die and 1.75x more likely to develop PD); also more likely to have lymphadenopathy and thrombocytopenia
MST: large cell 5m vs medium 9m vs small NR
Low MHC class II = shorter remission duration and ST (HR: 2.87x more likely to die and 3.49x more likely to develop PD)
MST: low 4m vs high 10.5m
What is the PFS* and MST in dogs with LSA treated with CCNU as a first line therapy? ORR? CR and PR?
PFS: 40d
MST 3.5m (111d)
ORR 52%, CR 35%, PR 17%
What is the PFS, and MST of dogs with LSA when treated with doxo/pred vs doxo/pred/CTX?
Main findings on this study?
Addition of CTX did NOT result in statistical improvement of ORR, PFS, or MST. Study was underpowered, however.
Doxo/pred/placebo - PFS 5 to 6m, MST 6 to 10m
Doxo/pred/CTX - PFS 8m, MST 14m
CR, PFI, MST with single agent doxo/pred in dogs with LSA of unknown phenotype?
ORR, CR, PFI, MST for B-cell?
ORR and CR* for T-cell?
Unknown: CR 78% PFS 4-6m, MST 5-10m
B-cell: ORR 100%, CR 70 to 86%, PFS 5-6m, MST 6-10m
Only chemo completion prognostic for PFS and ST; no diff when compared to historic controls that included T cell
T-cell: ORR 50%, CR 17%
CR to CHOP for T-cell vs B-cell canine multicentric LSA?
T-cell 88% (ORR 95%, PFI 5m, MST 8m)* largest study with specifically multicentric T-cell (no GI); 15% alive at 1 yr and 5% at 2 yr
B-cell 85 or >%
MOPP for T-cell: ORR 98%, CR 78%, PFI 6.3m, MST 9m)
25% alive at 2.5yrs
Main findings of RNA-loaded CD40-activated B-cells in dogs with spontaneous lymphoma?
Used CD40L transfected K562 cells to generate functional CD40-B cells from the peripheral blood of humans and dogs
It was administered to dogs in remission after induction of chemotherapy
Goal: Induce functional tumor-specific T cells in cancer patients
- CD40 activated B cells are highly efficient antigen-presenting cells capable of priming naive T cells, boosting memory T-cell responses and breaking tolerance to tumor antigens
- The use of tumor RNA as the antigenic payload allows for gene transfer without viruses or vectors and permits MHC-independent, multiple-antigen targeting
RESULTED IN:
-Higher % of dogs achieving a durable 2nd remission and improved lymphoma specific ST in relapsed dogs after rescue therapy
-Induced functional, antigen-specific T cells from healthy dogs and dogs with lymphoma
DID NOT affect: initial response, TTP, or ST compared to dogs tx with chemo alone
What is the ORR, CR, and PFI in dogs with NAIVE lymphoma when treated with alternating rabacfosadine/doxorubicin?
How does immunophenotype affect ORR?
Prognostic indicators (2)?
ORR 84% (CR 68%, PR 16%)
PFI 6.5m, if CR 7.2m
Immunophenotype predicted ORR:
95% - B cell
25% - T-cell
Substage and phenotype were associated with PFI; longer for B-cell
What is the ORR, CR, and PFI in dogs with B-cell LSA when treated with rabacfosadine in the RESCUE setting?
How does the PFI change for dogs with a CR or any response?
ORR: 74% (CR 45%, PR 29%)
PFI: 3.5m, 7m if CR, 6m with any response
No difference between doses used
What % of dogs with lymphoma vs myeloma develop dermatologic AE when treated with Tanovea?
Lymphoma: 25-37%
Myeloma: 50%
What is the most common phenotype, overall PFS and MST in dogs with colorectal lymphoma?
Does local therapy improve outcome?
B-cell, high-grade
PFS 3.6yrs
MST: 4-5yrs
Addition of local therapy to chemotherapy DOES NOT improve outcome
ORR, CR, PR to chemotherapy in dogs with colorectal LSA?
100% ORR
95% CR
5% PR
Prognostic factors in dogs with colorectal LSA (2)?
Younger dogs (<7yrs) = longer PFS (NR) and dz-specific MST
Hematochezia/substage b = longer PFS (NR)
What is the most common intestinal location in cats with LGL?
Most common phenotype?
IHC used for granules?
What % is NK origin?
Jejunum
granzyme B+ for granules (seen on cytology but not H&E sections)
CD3+ CD8+, CD20-, TCR gene rearrangement - most common
CD103 (integrin) - 60%
10% are NK origin (CD57+) and negative for B and T cell markers; C
What % of cats with LGL experience clinical benefit and a response when treated with chemotherapy?
35% - clinical benefit
30% - ORR
What is the overall TTP and MST in cats with LGL when treated with chemotherapy? MST w/o chemo? What % survives >7m?
TTP 50d
MST 2m; CHOP 60d, CCNU 60-130d
MST w/o chemo 2w
7% >6m SR
CHOP/COP ORR 30%
CCNU/Elspar ORR 56%
Negative prognostic indicators in cats with LGL (4)? Positive (1)?
- Substage b
- Circulating neoplastic cells
- Lack of chemo administration
- Lack of chemo response
Positive: chemo administration
What are the negative (4) and positive (3) prognostic factors identified in cats with nasal LSA?
Negative:
- Anemia
- Cribriform plate lysis
- Total RT dose of <32Gy
- BW of <4kg
Positive:
- Achievement of a CR
- Total RT dose of >32Gy
- Apoptotic index and Ki67 >40%
What is the overall MST in dogs with intermediate to high vs low-grade nasal LSA? Most common phenotype?
B-cell
Intermediate to high - MST 12.5m
Low - MST 2.3yr
No statistical difference in MST, but chemo alone had lowest MST of 5m vs RT + chemo MST of 15m
Most common primary and metastatic* intramedullary spinal tumor in dogs? Location?
Primary - ependymoma (neuroepithelial)
Metastatic- HSA and LSA per Withrow
HSA and TCC new paper; 33% each
T3-L3
Most common secondary brain tumor in cats vs dogs?
Cats - LSA #1, pituitary #2
Dogs - HSA #1, pituitary #2, LSA #3
What is the most common secondary intra-ocular tumor in dogs and cats?
LSA
Up to what % of dogs with LSA have ocular involvement? Most common abnormality?
37%
Uveitis
What is the PFS and OST in dogs with primary intrao-ocular LSA? Phenotype? CS? What % can develop neuro signs?
B-cell; considered stage V
Uveitis, endophthalmitis (inflammation of the anterior chamber), and 2/5 had abnormalities in contralateral eye
PFS/OST 6m
100% in one study
What is the PFS and MST in dogs with conjunctival LSA? Prognosis? How does it present?
Good prognosis
Considered stage I
PFS 7.5m, MST 18m
All unilateral, 2/4 had a discrete mass
Some can be cutaneous epi T-cell LSA
Some can develop LN involvement later on
What is the ORR and PFS of DTIC when used as a rescue in dogs with LSA?
ORR 35%
PFS 40d, if CR 144d
What population has been identified as having a higher risk for LSA development in Australia?
Neutered dogs (males and females)
What breeds are at higher risk for LSA development in Europe (4)?
Dobies, Rotties, Boxers, BMD
In Europe, what type of LSA do Rotties, Boxers, and dog de Bordeaux, most commonly develop?
Rotties - B cell
Boxers Bordeaux - T cell
In Europe, although Labs are not predisposed to developing LSA, what type do they most commonly get?
High grade T cell
What is the difference between Goldens in the USA vs Europe when it comes to LSA?
Unlike USA, they are not predisposed to LSA or TZL
What % of DLBCL and T cell LSA over-express PD-L1? What has this been associated with?
50% DLBCL
0% T cell
Increased expression of PD1 and PD1L in TIL and chemotherapy resistant cell lines in both B and T cells
Dogs with LSA tend to have a higher serum concentrations of what 2 things when compared to healthy dogs?
Lactate
B-hydroxybutyrate
How does the GI microbiota differ in dogs with asymptomatic LSA vs healthy dogs?
Asymptomatic LSA dogs have lower GI microbial diversity and higher degree of dysbiosis vs healthy dogs
How is the agreement of digital slide assessment with flow cytometry vs that of traditional glass slide assessment?
Lower
An s-phase fraction of > than ___% is consistent with high grade LSA. Sensitivity and specificity? What is it strongly associated with?
> 3.15%
Sensitivity 98%
Specificity 100%
Ki67
A Ki-67 of > than ___% is consistent with high grade LSA. Sensitivity and specificity?
Ki67 > 12.2%
96% sensitive
100% specific
What is the ORR, PFS, and MST in dogs with DLBCL, substage a, when treated with CHOP chemotherapy?
ORR 100% (82% CR, 18% PR)
PFS 8.5m
MST 11.5m
What are some identified PF for achieving a PR vs CR in dogs with DLBCL, substage a, when treated with CHOP (3)?
Thrombocytopenia at dx
Greater age at dx
High serum globulin concentration
What are some identified PF for a shorter PFS in dogs with DLBCL, substage a, when treated with CHOP (4)?
Thrombocytopenia at dx
Greater age at dx
PR as best response
Increased neutrophil count
MST 93d or < in these dogs
What is the ORR, CR, PFI, and MST of UK dogs with centroblastic DLBCL when treated with CHOP chemotherapy?
ORR 94%, CR 75%
PFI 6m, MST 11m (10.7m)
What is an identified prognostic factor for achieving a CR vs a PR in UK dogs with centroblastic DLBCL when treated with CHOP?
Entire dogs more likely to achieve CR
What are some identified prognostic factor (2) for achieving a longer PFI in UK dogs with centroblastic DLBCL when treated with CHOP?
Absence of anemia at dx
Pre-treatment neutrophil:lymphocyte ratio <9.44
What are some identified prognostic factor (4) for achieving a longer ST in UK dogs with centroblastic DLBCL when treated with CHOP?
Lymphocyte:monocyte ratio >1.43
Neut:lymph ratio <11.44
Combination of induction and rescue therapy
Increased number of doxorubicin doses
Upregulation, phosphorylation, and nuclear localization of what 2 TF have been noted in lymphocytes from dogs with DLBCL vs those from healthy LN?
STAT3 and ERK1/2
What is the ORR in chemotherapy naive lymphoma patients when given VBL? Doses used?
7% PR at 2 mg/m2
60% PR at 2.5 mg/m2 - 80% developed neutropenia 1 week post
What is the ORR and DFI of VBL when used as a rescue agent in dogs with LSA? Dose used?
VBL at 2.6mg/m2
ORR 26% (CR 8%, PR 18%)
DFI 30d
6% grade III or IV neut
In dogs with B cell lymphoma tx with doxo + pred, what has been addociated with a longer PFS and MST?
Chemo protocol completion
ORR, CR, PFS/DFI, and MST in dogs with T-cell LSA treated with Morgan vs Brown LOPP? 2-yr SR?
Morgan:
ORR 94%, CR 83%, PR 11%
PFS 14.4m, MST 17m
54% 1-yr PFS, 29% 2-yr PFS
Brown:
ORR 97%, CR 90%, PR 7%
DFI 6m, MST 8m
39% 1-yr SR, 25% 2-yr SR
AE to Morgan vs Brown LOPP in dogs with T-cell LSA?
Morgan:
86% overall (higher)
51% myelosuppression; grade 3+ neut/thrombo in 80%
74% GI; only 13% grade 3+
23% overall hospitalized; 11% if not including post induction
40% required dose reductions
Brown:
42% overall
Only 18% required dose reduction
How do CSC behave in dogs with B and T cell LSA vs LN samples from a healthy dog?
% of tumour cells expressing CSC markers were significantly increased in dogs with BCL, compared with B cells from normal lymph nodes. Similar results in T-cell.
CSC flow cytometry markers in B vs T cell lymphoma?
B-cell: higher expression of CD117, CD90, CD34, Oct 3/4 vs normal B cells
T-cell: higher expression of Oct 3/4 and downregulation of CD90 vs normal T-cells
What is the ORR and T-cell RR, TTP, duration of response and AE of verdinexor (KPT-335) in dogs with T-cell LSA (naive and progressive)?
MTD?
ORR: 37%, T-cell 71%
TTP 30d
Response duration 18d
AE: 95% grade 1-2
anorexia 45%
weight loss 31%
vomiting 26%
Hepatopathy also reported
1.75mg/kg PO BID 2-3x per week
What is verdinexor?
Oral selective inhibitor of nuclear export (SINE) ; reversibly binds to XPO1, which is responsible for moving p53, p21, pRb, FOXO, NF-KB into the cytoplasm
Based on geographical location within the USA, which locations have the longest vs shortest PFS when treated with chemo?
North - 8m
South - 6m
West - 4m
Dogs with centroblastic polymorphic DLBCL have a higher chance of 2-yr survival if what 4 factors are present?
BW >10kg
Normocalcemia
No BM involvement
No steroids
MST of dogs with Burkitt’s LSA?
15d
When dogs with LSA are treated with LPP in the relapse setting, which ones are more likely to respond?
Those getting a higher procarb dose
In geriatric dogs (14 or>) with LSA treated with COP or CHOP, what is the ORR, CR, duration of response, MST, grade 3 AE?
Negative PI (1)?
Most common phenotype?
B-cell 95% CR Duration of response 6m MST 7m AE: 27% (similar to historic CHOP data)
NPI: Anemia shorter PFI
What are some negative prognostic indicators for PFI and MST in geriatric dogs with B-cell LSA?
PFI: shorter if anemia present
MST: shorter if BW 13kg or >
American Golden Retrievers are more likely to have TZL vs BCL in which geographic locations?
North East
East North Central regions
How its T-zone (clear cell) lymphoma characterized?
A variant of PTCL-NOS characterized by clonal expansion of T-cells that lack expression of CD45, a pan-leukocyte antigen, within the paracortex and medullary cords of LN resulting in compression of germinal centres. The cells are small to intermediate in size with very rare mitoses.
Phenotype: high MHC class II, low-moderate CD21+, CD5+, CD45- Not always CD21+ but high % can be +
What % of older Golden Retrievers without clinical TZL have peripheral circulating TZ cells compared to non-Goldens?
Goldens - 31%
Non-Goldens - 14%
What % of older Goldens without clinical TZL that have circulating TZ cells also have clonal TCR gamma gene rearrangement vs Goldens without TZ cells?
Golden’s WITH TZ cells and clonal TCR - 34%
Golden’s WITHOUT TZ cells and clonal TCR - 20%
In dogs with nodal marginal lymphoma, what % is substage b, what % has stage V dz, splenic, hepatic, and BM involvement?
Most common extranodal site?
Substage b - 34% Stage V dz - 100% Spleen - 97% Hepatic - 80% BM involvement - 60% Extranodal site - lungs
How is the neoplastic lymphoid population described in dogs with nodal MZL?
Medium-sized CD21+ and +/- CD70a+ lymphocytes
Low mitotic activity
Histopath: diffuse growth, loss of follicle architecture, thinning of capsule
What is the ORR, CR, PR, TTP and lymphoma-specific MST in dogs with nodal MZL when treated with CHOP? Overall outcome?
Poor outcome
ORR 100%, CR 80%, PR 20%
TTP 5m
MST 9m (260d)
Negative prognostic factors for ST in dogs with nodal MZL (2)?
Substage b
Elevated serum lactate dehydrogenase
What % of dogs with hypercalcemic LSA have mediastinal involvement?
43%
What % of dogs with multicentric T-cell LSA have mediastinal involvement?
54%
Mediastinal lymphoma is almost always exclusively T-cell and hypercalcemia is most commonly associated with this form of LSA.
What % of dogs with mediastinal lymphoma are hypercalcemic at diagnosis?
68%
Most common phenotype and cytomorphology in dogs with mediastinal LSA?
T-cell
Lymphoblastic high-grae
What % of dogs with mediastinal T-cell LSA are substage b? Most common clinical signs?
85% - substage b
71% - lethargy
Anorexia
PU/PD
What % of dogs with mediastinal T-cell LSA have pleural effusion at diagnosis?
45%
In dogs with mediastinal T-cell LSA, what is the ORR, CR, PFS, and OST when treated with CHOP chemotherapy?
ORR 93%, CR 70%
PFS 4.5m
OST 6m
PPI in dogs with mediastinal T-cell LSA when treated with CHOP?
CHOP chemo - improved PFS and OST
Lack of pleural effusion - improved OST
Is there a difference in outcome in dogs with relapsed multicentric lymphoma when treated with TMZ vs TMZ + doxorubicin? Overall MST?
No; overall MST 40d
TMZ alone: ORR 32%, TTP 15d, MST 40d
TMX/doxo: ORR 60%, TTP 19d, MST 60d
Most common LSA in CNS in dogs?
DLBCL; usually an extension vs primary
CSF analysis in dogs with CNA LSA is diagnostic in what % of cases?
~70%
Increased TNC from which 95-100% are atypical lymphocytes and increased TP
Overall MST in dogs with CNS LSA?
170d (5.6m)
Phenotype of epitheliotropic LSA in dogs?
CD8+
ORR, CR, remission duration if CR, and MST in dogs with CETCL treated with CCNU?
ORR 80%, CR 30%
CR duration 4.5m (132d)
MST 6m
Prognostic factors in dogs with CETCL?
Positive PI:
- Mucocutaneous or mucosal lesions vs cutaneous
- For cutaneous lesions, the use of chemo and the presence of solitary lesions
- For mucocutaneous, younger age and presence of solitary lesions
Sensitivity of a moth-eaten spleen in cats with LSA on AUS?
13% sensitive
85% specific
What is the ORR to Elspar in cats with LSA? How is it when compared to dogs?
30% ORR (CR 15%, PR 15%)
Shorter duration of response; <7d
Sensitivity and specificity of flow cytometry for LSA diagnosis in cats?
What needle gauge is preferred in order to provide a highly cellular sample?
92% sensitive
100% specific
21 gauge needle
What is the most common Hodgkin’s like lymphoma in cats? Presentation? Immunophenotype? Prognosis?
Lymphocyte-histiocytic (RS cell variant); usually small to medium sized lymphocytes and large histiocytic looking lymphocytes
Reactive CD3+ T cells in the background
Lymphohistiocytic cells positive for BLA 36 and CD79a -> B-cell
Lymphadenopathy of 1 or > enlarged LN in the head/neck region
Prognosis: usually excellent
W/sx - DFI 1yr
W/o tx - MST 7m-4yr ST
Can sometimes regress on its own and then come back
Can become aggressive
Usually cats older than 6 yrs
What is the ORR, CR*, DFI, and MST for cats with various anatomic forms of intermediate to high-grade LSA when treated with intraperitoneal L-COP? 1 and 2yr SR?
ORR 96%, CR 77%, PR 19% DFI 14m (421d) MST 13m (388d) 55% 1-yr SR 47% 2-yr SR
Which anatomic in cats with LSA location has the shortest DFI when treated with intraperitoneal L-COP?
GI 7.6m < Nasal 13m < Peripheral 14
Most common AE in cats with intermediate to high-grade LSA when treated with intraperitoneal L-COP?
Vomiting - 42%
Also anorexia and weight loss
Prognostic indicators in cats with intermediate to high-grade LSA when treated with intraperitoneal L-COP (2)?
Younger age = more favorable response
CR = long-term ST
Most common cause of febrile neutropenia in cats?
#1 CCNU #2 Vincristine
Most important PI in cats with GI LSA?
Response to therapy
ORR, PFS, MST in cats with intermediate to high grade LSA treated with DMAC in the rescue setting? AE?
26% clinical benefit (no CR)
PFS 14d
MST 17d
16% grade 4 neutropenia
What % of cats with GI LSA have concurrent IBD?
60%
When the human WHO classification system is applied to cats with alimentary LSA, what is the predominant form seen in the stomach, SI, mesenteric LN, and ileocecocolic junction, large intestine?
Stomach - DLBCL
SI - EATL type I (48%) and II (42%)
Mesenteric LN - T-cell
Ileocecocolic - DLBCL
Phenotype statistically associated with associated with location
When the human WHO classification system is applied to cats with alimentary LSA, what are the 3 most common forms of alimentary LSA in cats?
1 EATL type I - 41%; transmural T-cell LSA, large cells; extension into submucosa and muscularis propia
What are the 2 most common alimentary forms of LSA in cats when using the feline classification system?
Mucosal - usually low grade, small-cell, T cell
Transmural - usually high-grade, small (40%) or large (60%), B or T cell; LGL is a large cell subtype
What % of alimentary LSA in cats are T vs B cell? Which form of LSA is more common within the phenotypes?
T- cell: 80%, usually mucosal (80%)
B-cell: 20%, usually transmural (95%)
What % of cats with LGAL develop large cell GI LSA?
3.7%
Most common location for alimentary LSA in cats?
SI; rarely in stomach and LI
In cats with alimentary LSA, what immunophenotype is most commonly associated with solitary/multifocal vs diffuse dz?
T-cell diffuse
B-cell solitary or multifocal; multiple common
Most common locations for low grade alimentary LSA?
Jejunum and ileum
What % of cats with LGAL exhibit epitheliotropism?
40%
What has been recently noted in cats with LGAL and COX-2 expression (2)?
COX-2 protein expression is present in 1/3 of cats with LGAL, but no difference when compared to cats with IBD.
COX-2 mRNA levels are higher in cats with LGAL vs IBD or healthy cats
What are the 2 most common subtypes of transmural large-cell LSA in cats?
LGL - most common one*
DLBCL
Most common subtype of large-cell transmural alimentary LSA in cats?
Large granular LSA - 82%
Overexpression of ____ mRNA has been noted in cats with LGAL vs IBD.
MDR1
What % of cats with discrete intermediate to high grade LSA develop intestinal perforation post chemotherapy induction?
17% (20-90d post)
What is the most common complication in cats with alimentary LSA that undergo full thickness biopsies? Prognostic indicators for complications?
Transient hypo or anorexia - 11%
Other: hyperthermia, pancreatitis
NO dehisence!!
No identified prognostic variables
Low albumin NOT prognostic (as opposed to dogs <2.5)
Besides flow cytometry, what test has the best sensitivity and specificity for differentiating small cell GI LSA vs IBD?
PARR - 90% sensitive
Histopath - 99% specific
How has abdominal RT been combined with chemotherapy in treatment naive cats with abdominal or multicentric lymphoblastic/large cell lymphoma?
Response and outcome?
6 week CHOP chemo 2-week holiday 1.5Gy x 10d (M-F) 5/8 had durable remission of >266d (9m) Overall, well tolerated
2 cats relapsed
1 euthanized for unknown reasons
What is the MST in cats with different types of GI LSA when treated with abdominal RT in the rescue setting? Protocol? AE?
8Gy x 2d
MST 7m
Minimal RT SE, 1 cat had self-limiting loss of appetite
What % of cats with LGL have extra-intestinal involvement?
Three most common locations?
85%
LN>liver>spleen>kidneys>lungs>bone marrow
Epitheliotropism common
LGAL accounts for what % of feline alimentary LSA?
60-75%
Most common form
What % of cats with LSA have pulmonary involvement?
13%
In cats, to what forms of LSA is pulmonary LSA associated (3)?
Mediastinal
Alimentary
Multicentric
Most common pulmonary lesions in cats with LSA?
No gross lesions 56%
Masses 25%
Nodules 20%
Most frequent radiographic pulmonary pattern seen in cats with LSA and pulmonary involvement?
Peribronchial-vascular infiltrative pattern
Most common phenotype and subtype in cats with LSA and pulmonary involvement?
B cell (90%) DLBCL (60%)
What are the identified risk factors for feline intestinal carcinoma (3)?
Age (10-12 yrs)
Males
Siamese - 1.8x increased risk for intestinal neoplasia and 5x increased risk for ACA
What IHC markers are used for GISTs (5)? Most sensitive ones (2)?
CD117 - 95-100% DOG-1 CD34 VImentin SMA - 30% (usually negative)
CD117 and DOG1; will catch the ones negative for CD117
Discovered-on-GIST 1 (DOG1) is a Ca-dependent Cl channel involved in generation of slow waves from the interstitial cells of Cajal
Where are mutations in the c-kit gene located in dogs with GIST?
Exon 11 of juxtamembrane domain of KIT
Results in constitutive activation
Mutations: deletions, ITD, and point mutations
What techniques can be used to detect c-kit mutations in dogs with GIST (2) and which one is more likely to detect a mutation?
RT-PCR: 72.4% detected
Conventional PCR: 32.6%
What is the most common KIT staining pattern in dogs with GIST? Is it associated with c-kit mutation status?
Diffuse cytoplasmic - 70%
partial/focal stippled cytoplasmic - 30%
NOT associated with c-kit mutation status
Why can females develop perianal gland adenomas after being spayed? What is another reason?
Loss of estrogenic inhibition
Testosterone-secreting adrenal tumor
What are some negative prognostic indicators in dogs with AGASACA (10)?
Tumor size: > 9cm2 or >2.5cm LD
Any mets: LN and distant
Advanced clinical stage
Lack of sx
Lack of chemo
Tx with chemo alone
LN mets and extirpation
Tx with platinums (shorter DFI, another study showed it decreases risk of local recurrence)
Hypercalcemia (newer studies say its not)
Some histopath changes (see next index card)
What are some negative histopathologic PI in dogs with AGASACA (7)?
Decreased E-cadherin expression
Solid growth pattern
Moderate or marked peripheral infiltration
Necrosis
Lymphovascular invasion
Cellular pleomorphism
MI 8 or >
What is the TTP and MST in dogs with early stage (<3.2cm) AGASACA w/o mets when treated with sx alone?
Recurrence rate and later metastasis?
TTP 2.4yrs
MST 3.4 yrs
RR 20%
Mets in 26% at 1yr or later
What is the MST in dogs with AGASACA that develop local recurrence and are treated with a 2nd surgery?
Overall 2 yrs
After 2nd sx 9.5m
What is the TTP and MST in dogs with AGASACA when treated with sx and 4 doses of carboplatin? Did chemotherapy make a difference in ST?
TTP 13m
MST 2 yrs
Chemo did not make a difference
What is the MST in dogs with AGASACA when treated with sx and melphalan?
20m
What is the MST in dogs with AGASACA treated with sx, carboplatin, and hypofractionated RT?
19m
What is the PFI and MST in dogs with stage 3b AGASACA when treated with sx vs hypofractionated RT?
Sx - PFI 5.3m, MST 6m
RT - PFI 11.5m, MST 15m
IIIb - T any size, nodal mets >4.5cm (vs a, <4.5m)
Dog with AGASACA, no nodal metastasis, hypercalcemic – what is the best treatment?
Pamidronate and fluids, sx alone, sx and hypofractionated RT to the node bed, Sx and Palladia
How to treat?
What % of AGASACAs express PDGFRa and b? VEGFR2 cytoplasmic staining?
Alpha - 100%
Beta - 17 to 19.5%
VEGFR - 80%
What are late SE that can occur with adjuvant RT for AGASACAs? How can this be minimized?
Rectal stricture or perforation
Minimize by using <3Gy per fraction
A study evaluating an IMRT theoretical 3.8 Gy x 12 protocol for dogs with stage IIIb AGASACA determined that in almost half of the patients, there was a ___% risk of late spinal cord toxicity. There was ___% risk of ____ in 33% of patients.
5% or > of late spinal cord toxicity
> 15% risk of myelopathy in 33% of patients
In dogs with GIST treated with Palladia, what is the median PFI when used in the gross vs microscopic dz setting? Biological response rate in dogs with gross disease?
Biological response 71% (2 CR, 1 PR, 1 SD)
PFI in gross dz 2.3yrs (for responders)
PFI in microscopic 1.3yrs
Negative PI for a shorter PFI in dogs with GIST treated with Palladia?
Metastasis at dx
High mitotic index (<5, 5-10, >10)
What is the TTP and MST in cats with salivary gland carcinoma when treated with RT and +/- surgery? Negative PI (2)?
TTP: 5m
ST: 2-19m
Advanced clinical stage
Compared to dogs, cats have a higher metastatic rate and poorer long term prognosis
What is the most common exocrine pancreatic tumor in cats?
Metastatic rate at diagnosis?
Most common clinical signs at presentation?
Pancreatic adenocarcinoma
32% have mets at dx
Weight loss (68%), anorexia (53%), vomiting (41%), palpable abdominal mass (41%)
What paraneoplastic syndrome can be seen in cats with exocrine pancreatic carcinoma?
Alopecia
Acute, progressive, non-scarring, bilaterally symmetric; predominantly involves the limbs, but can include the ventrum, head, and trunk
What is the most common comorbidity in cats with pancreatic carcinoma?
Diabetes mellitus - 15%
Other:
Heart dz or murmur (21%)
Hyperthyroidism (18%)
Overall MST in cats with pancreatic carcinoma?
What is the MST in cats with pancreatic carcinoma treated with sx and chemo?
1-yr SR?
What type of surgery is performed?
Overall 3m
MST w/sx and chemo 5.5 to 10.5m
*10.5 if no mets
8.8% 1-yr SR
Complete pancreatectomy or Whipple’s procedure (pancreaticoduodenectomy)
Negative PI in cats with pancreatic carcinoma (3)?
Peritoneal effusion (30d)
Tx with NSAIDs alone (26d)
Lack of sx and/or chemo (improves ST, 165d)
MST <1m
What chemotherapy has been shown to have clinical benefit in cats with pancreatic carcinoma?
Gemcitabine - 82%
Most common gastric mass in lesser curvature/antrum of stomach in dogs? CS: GI bleed, high BUN.
Gastric ACA - #1 gastric tumor in dogs (80%)
Most common location: lesser curvature and antrum
Metastatic rate of gastric ACA in dogs? Locations?
70-80% metastatic rate
lymph nodes #1, liver #2, lungs #3
Gastric ACA in dogs are more common in what sex and breeds (2)?
Males
Belgian Shepherd and Rough-Coated Collie
Ulcers and bleeding can occur in ___% of dogs with gastric ACA. Because of this, what is a common CBC finding?
50%
Microcytic hypochromic anemia
What is the 2-week and 3-month SR in dogs with gastric neoplasia (benign and malignant) undergoing pylorectomy and gastroduodenostomy (Billroth 1)?
What % of dogs undergoing this surgery survive to discharge?
MST?
75% 2-week survival rate
60% 3-month survival rate
88% survived to discharge
MST 1-2m (generally <6m)
Billroth 1 - resection of pyloric antrum (pylorectomy) and gastroduodenal anastomosis (gastroduodenostomy)
Three most common complications in dogs with gastric neoplasia undergoing pylorectomy and gastroduodenostomy (Billroth 1)?
hypoalbuminemia (63%) anemia (58%) transfusion (33%) hypotension (17%) hypoglycemia (17%) aspiration pneumonia (13%) pancreatitis (13%) sepsis due to dehiscence (8%)
Negative PI (on univariate) in dogs with gastric neoplasia undergoing pylorectomy and gastroduodenostomy (Billroth 1) (2)?
Preoperative weight loss
Malignant cancer
Most common GIST location?
Cecum
Second most common gastric tumor in dogs? Location? Signalment?
LMA
Stomach cardia, grow into lumen, discrete, pedunculated
Always focal
Commonly seen in older dogs ~15yr; Beagles
According to CT findings in dogs with gastric tumors, what tumor is most likely associated with larger LN?
Gastric LSA
According to CT findings in dogs with gastric tumors, is LSA more likely to be segmental or diffuse?
Segmental 60%
Diffuse 40%
According to CT findings in dogs with gastric tumors, is ACA more likely to be segmental or diffuse?
50:50
What are the intraoperative and perioperative mortality rates in dogs with massive HCC undergoing sx?
intraoperative 4.8%
perioperative 8-12%
What is the perioperative mortality rate in cats with massive liver tumors undergoing sx?
22%
In cats with massive liver tumors undergoing sx, what % survives to hospital discharge and what % lives >40d?
78%
61% lived >40d (multiple liver tumors)
Complication rate in dogs and cats undergoing liver sx for massive tumor removal?
Most common complication?
Dogs - 30%
Cats - 22%
Hemorrhage; 17% of dogs and 44-61% of cats undergoing liver lobectomy need a blood transfusion
What are some identified prognostic factors in dogs undergoing sx for massive HCC (8)?
Surgical excision vs palliative care (MST >1460d vs 270d); non-surgical cases 15.4x more likely to die
Increased ALT and AST
Increased ALP to AST ratio
Increased ALT to AST ratio
Side of liver involvement; higher risk of intra-op complications for R-sided tumors, but no difference in ST
Lethargy or tachypnea at presentation
Experiencing an anesthetic complication
Requiring a blood transfusion associated with failure to survive to discharge
What are some prognostic factors in cats with liver tumors treated with sx (3)?
Abdominal effusion
Preoperative anemia
Need for transfusion
Shorter MST
What is the most common primary hepatobiliary tumor in cats overall?
Bile duct adenoma (biliary cystadenoma) - 52% of all liver tumors
How do bile duct adenoma (biliary cystadenoma) loos grossly? Sex predisposition? CS?
Cystic appearance
Even distribution between focal vs multifocal
Male
Typically asymptomatic until mass effect occurs
What is the most common primary malignant hepatobiliary tumor in cats? Metastatic rate and locations?
Bile duct carcinoma (cholangiocarcinoma)
67-80% metastatic rate; LN, lungs, carcinomatosis, etc
PNS alopecia reported (and with HCC)
What is the second most common malignant hepatocellular tumor in cats?
Hepatocellular carcinoma
Metastatic rate and MST with and w/o sx in cats with HCC?
Met rate - 0%
MST: w/o surgery 1.4yrs vs w/sx 2.4yrs
What are the most common chemistry abnormalities in cats with HCC (4)?
AST elevated in >90%
ALT and ALP elevated in >70%
Hyperbilirubinemia in >40%
What viruses are associated with HCC in humans?
Hepatitis B and C
Woodchuck: Woodchuck hepatitis virus
In dogs vs cats, are primary vs metastatic tumors more common?
Dogs - metastatic
Cats - primary (usually benign)
Recently, upregulation of ___ mRNA was noted in dogs with HCC.
MET
In dogs with concurrent splenic and hepatic masses, what % had malignancies in both organs?
Of those with concurrent malignant lesions, what % had the same malignancy?
Most common malignancy?
48% - malignant in both organs
93% - same in both organs
HSA - 77%
ORR of Palladia in dogs with non-resectable liver tumors?
50% (PR) in 3/6 dogs
What % of dogs with HCC develop tumor reduction post trans-catheter arterial embolization?
100%
What is an identified predisposition for intestinal tumors in both dogs and cats?
Male sex
Of dogs with inflammatory intestinal polyps that underwent a 2nd biopsy, what % developed adenoma and ACA?
36% adenoma
20% ACA
In the study of dogs that developed adenomas and carcinomas after an initial diagnosis of polyps, what was also noted?
Inactivation of APC gene
Accumulation of B-catenin in cytoplasm -> translocation to nucleus -> promotion of Wnt associated genes
Most common sited for GIST in dog?
Cecum #1
Colon
What drug is used in humans with GIST?
Imatinib (Gleevec)
Can rescue with Sunitinib when Imatinib fails
In dogs, what are the most common locations for intestinal lymphoma?
Equal distribution between stomach and SI (LI less likely)
What dog breeds are predisposed to developing intestinal T-cell LSA (7) according to a Japan study?
Shiba dogs, German shepherds, Cairn terriers, Boston terriers, Papillons, Pugs and Maltese
What is the most common phenotype for intestinal T cell lymphoma in Shiba dogs in Japan?
CD3+, granzyme B+
Regardless of small or large cell
What is the most common phenotype and lesion distribution in dogs with small cell intestinal LSA?
T-cell
Diffuse - 38%
Discrete/multifocal - 23%
What is the most common clinical sign in dogs with small cell T-cell intestinal lymphoma?
Diarrhea #1
Weight loss
What are the 3 most common US abnormalities in dogs with small cell T-cell intestinal lymphoma? What % of dogs have a normal AUS?
Abnormal wall layering - 54%
Hyperechoic mucosal striations - 54%
Thickened muscularis - 34%
Normal - 38%
Mild lymphadenopathy - 46%; only 1 had LSA confirmed
What % of dogs with with small cell T-cell intestinal LSA exhibit epitheliotropism?
60%
What is the overall MST and MST of chemotherapy treated dogs (14/17) with with small cell T-cell intestinal LSA?
Overall MST 9m
Chemo tx dogs MST 14-21m
Identified prognostic factors in dogs with small cell T-cell intestinal LSA (4)?
Anemia = shorter ST
Weight loss = shorter ST
Tx with steroids + alkylator = longer ST vs steroids alone
Response to therapy = longer ST
What is the ORR to chemotherapy in dogs with small cell T-cell intestinal LSA?
70%
What % of canine small cell T-cell intestinal LSA co-express CD20?
48%
2 common chemistry abnormalities in dogs with small cell T-cell intestinal LSA?
Hypocobalaminemia -71%
Hypoalbuminemia - 69%
Most common intestinal location in dogs with small cell T-cell intestinal LSA?
Duodenum
Histopathologic description of dogs with smal-cell T-cell intestinal LSA?
Lymphocytic infiltrates within the intestinal villous lamina propria and epithelium.
Infiltrates were often more pronounced in the villous tips
Most common phenotype in dogs with large-cell intestinal LSA?
T-cell
What % of dogs with large cell intestinal LSA have intestinal + LN involvement vs intestinal involvement alone?
Intestinal + LN 48% (94% had LSA confirmed on LN)
Intestinal alone 40%
MST in dogs with large cell intestinal LSA when treated with multiple therapies?
2-2.5m
Dogs tx with CCNU have a numerically longer MST, but not statistically significant
No differences in outcome based on tx
Most common AUS abnormalities in dogs with high-grade intestinal LSA (4)?
#1 Thickened intestinal wall with loss of layering #2 presence of ≥ 1 discrete mass #3 ulceration
What are some negative prognostic indicators in dogs with high-grade intestinal LSA (4)?
Diarrhea
Anorexia
Septic peritonitis
Dz outside of intestines alone
What are the 3 most common causes of hypercalcemia in cats?
#1 idiopathic #2 kidney disease #3 neoplasia
What % of hypercalcemic cats have cancer?
1/3 or 33%
What are the most common causes of hypercalcemia of malignancy in cats?
Lymphoma and SCC
PTHrp mediated
What % of cats vs dogs with MM are have hypercalcemia?
Cats: 10-25%
Dogs: 15-20%
What is the main MOA for hypercalcemia in dogs and cats with MM?
IL-1B (osteoclast activating factor)
Expected BW abnormalities in dogs with primary hyperparathyroidism?
iCa and Tca - high
PTHrp - zero
PTH - normal or high
Ph - low (if neoplastic too)
What non-neoplastic infectious dzs can cause a monoclonal gammopathy (8)?
Babesia Ehrlichiosis Leishmaniasis FIP Coccidioides Heartworm Bartonella henselae Strep zooepidemicus in cats Chronic pyoderma Amyloidosis
Clinical case of TCC with hypertrophic osteopathy. What to do next?
Tumor excision
Can consider anti-inflammatory steroids, NSAIDs and/or bisphosphonates
What % of tumor bearing dogs have thrombocytopenia prior to therapy?
36% prior to therapy
Highest with lymphoproliferative disorders - 58%
Thrombocytopenia is higher in dogs with which class of tumors?
Lymphoproliferative disorders - 58%
What % of dogs and cats with MM have thrombocytopenia?
Cats 50%
Dogs 33%
Most common cause of thrombocytopenia in cats?
Lymphoma
What % of dog with HSA have thrombocytopenia?
75-97%
DIC cause of consumptive thrombocytopenia in ___% of dogs with cancer.
40%
What % of dogs with HSA and cats with splenic MCT have an abnormal coagulation profile?
Cat splenic MCT = 90%
Dog HSA = 50%
What is the most common PNS in dogs and cats with LSA?
Non-regenerative anemia
Non-regenerative anemia can be present in what % of dogs and cats with MM?
Dogs: 70%
Cats: 50-65%
Anemia more common than thrombocytopenia in MM*
What is the most common cutaneous tumor in cats? Biologic behavior and metastatic rate?
Basal cell tumor - 23% overall
(10 to 26%)
Usually benign. A study of 97 feline BCT had 10% categorized as malignant based on stromal invasion, vascular invasion, necrosis, high MI, LN mets (1 cat); another study had 1 cat with pulmonary mets
What is the most common malignant ear canal tumor in dogs and cats?
Ceruminous gland adenocarcinoma
In dogs and cats, are malignant vs benign tumors of the ear canal more common?
Dogs - uncertain
Cats -malignant
What canine breeds are at increased risk for developing ear canal ceruminous gland ACA (2)?
Cocker Spaniels and GSD
How is the metastatic rate in dogs and cats with ear canal ceruminous gland ACA?
Low and uncommon, but increases over time
Dogs - LN 3.3%, lungs 8.5%
Cats - LN 9%, lungs 0%
What is the TOC in dogs and cats with ear canal ceruminous gland ACA? Why?
TECA and BO
Recurrence is lower vs LECA
What are negative prognostic factors in dogs with ear canal ceruminous gland ACA (1)?
Extension beyond ear canal (cartilage invasion)
MST 6m vs w/o (confined) 30m
What are negative prognostic factors in cats with ear canal ceruminous gland ACA (4)?
MI of ≥ 3 (MST 12m vs 180m)
Neurologic CS (MST 15.5m vs 1.5m)
Histology (ACA MST 49m vs SCC 3.8m)
Extension beyond ear canal/cartilage invasion (MST 4m vs w/o 22m)
What are negative prognostic factors in dogs with digital melanoma (8)?
- Mitotic index ≥ 3
- Ki67 index ≥ 15
- ≥ 20% nuclear atypia
- Distant mets
- Degree of pigmentation (scale 0-2, 2 is favorable)
- Junctional activity
- Level of infiltration/extension beyond dermis
- Ulceration
What % of dogs with digital melanoma have metastasis at presentation?
30-40%
Picture of cytology (SCC) lab with lysis of P3. What is the metastatic rate at diagnosis and later on?
What % has lysis on xrays?
At dx 9%
Later on 23%
80% have lysis on xrays
What are identified prognostic factors in dogs with oral melanoma (14)?
- Ki67 index ≥ 19.5% (shorter DFI and MST)
- MI ≥ 4/10 hpf
- ≥ 30% nuclear atypia
- Co-expression of PDGFR a/b (37%, shorter DFI and MST)
- Higher % of intratumoral Tregs
- Stage of dz
- Size of tumor
- Lymphatic invasion
- Distant mets
- Degree of pigmentation
- Female sex
- Adjuvant therapy
- Intralesional excision
- > 12yrs of age
What are the negative prognostic indicators identified in dogs with lip melanoma (7)?
- Mitotic index ≥ 4/10 hpf
- Ki67 index ≥ 19.5%
- ≥ 30% nuclear atypia
- Distant mets
- Degree of pigmentation
- Junctional activity
- Level of infiltration/deep with bone involvement
Cutaneous melanomas are often benign if they are not in a mucocutaneous location. What are the negative prognostic indicators for this location in dogs (8)?
- Ki67 index ≥ 15%
- MI ≥ 3/10 hpf
- ≥ 20% nuclear atypia
- Extension beyond dermis/level of infiltration (Breslow thickness: >0.75cm = risk of recurrence/mets, >0.95cm = unfavorable outcome)
- Ulceration
- Distant mets
- Lymphatic invasion
- Degree of pigmentation
What combination of IHC markers is the most sensitive and specific when trying to differentiate an amelanotic from a STS (3)?
What is the sensitivity and specificity of this combination?
What other markers (2) and what other histologic characteristic (1) can be used to help dx melanoma?
What markers are 100% specific, but have a low sensitivity (3)?
Melan A, PNL2, tyrosinase (TRP1/2): 93% sensitive and 100% specific
S-100, MITF: highly sensitive, but less specific (will also stain sarcomas)
Others: vimentin, NSE - positive for both
100% specific, but low sensitivity: HMB-45, tyrosinase, tyrosinase hydroxylase
Presence of junctional activity = proliferation of neoplastic cells at the dermoepithelial junction
NOT ALL WILL STAIN WITH MELAN A
What IHC marker can be used to differentiate a malignant melanoma from a melanocytoma and how does the expression of this marker differs between them?
RACK1 (receptor for activated C kinase 1)
Malignant melanomas stain homogeneously and benign ones heterogeneously
Correlates with cell and nuclear size
What 2 transcription factors haven been associated with increased risk of death in dogs with melanomas? Which one was of prognostic significance on multivariate analysis?
FOXP3, IDO (indoleamine 2,3-dioxygenase)
Increased risk of death associated with higher:
- # FOXP3/HPF
- % of FOXP3+ infiltrating lymphocytes
- # IDO+ cells/HPF
Only #IDO+ cells/HPF prognostic on multivariate
What is the overall MST and PFS in dogs with anal sac melanoma treated with a combination of therapies?
MST 3.5m (107d) PFS 3m (92.5d)
What ICC stain has been shown to be 100% sensitive and specific for the diagnosis of amelanotic melanoma? How does this differ when compared to routine cytology stains?
Melan A
Routine cytology: 67% sensitive, 86% specific
When evaluating histopathology LN samples in dogs with melanoma and trying to differentiate malignant melanocytes from melanophages, the addition of Melan A has been reported to change the final diagnosis in what % of samples?
47%
14 from metastatic to reactive
1 from reactive to metastatic
What is the reported range of complete agreement between cytology and histopathology for the diagnosis of metastatic LN in dogs with melanoma?
30- 50%
POOR
What are the reported ranges for ORR, CR, PR, and PFI, in dogs with OMM when treated with hypofractionated RT? Time to metastasis?
ORR 83-100%
CR 50-70%
PR 25-30%
Time to mets 310d
What is the reported overall PFS and MST in dogs with OMM when treated with RT?
1 and 2 yr SR?
PFS 5-8m
MST 4-12m (stage dependent)
1-yr SR 35-50%
2-yr SR 20%
What is the reported rec
OMM when treated with RT in the microscopic vs gross dz setting?
Microscopic 25%
Gross 45%
What is the MST for stage I, II, III, and IV oral MM in dogs when treated with RT and adjuvant sx or chemo? Any prognostic factors identified?
Stage I: 2yrs (758d)
Stage II: 9m (278d)
Stage III: 5.5m (163d)
Stage IV: 2.5m (80d)
Stage
What has been shown to affect prognosis in dogs with OMM treated with different forms of RT (6)? These dogs were also +/- treated with sx and chemo.
- Stage; stage I dz vs higher and stage III dz tx with orthovoltage (shorter MST)
- Tumor volume/size (>5cm3 shorter MST)
- Bone involvement (shorter TTP and MST)
- High VEGF (shorter TTP and MST)
- Location (rostral better)
- RT in the microscopic dz setting (better)
What % of dogs with OMM is reported to develop oronasal fistulas and bone necrosis when tx with RT?
5.4% oronasal fistula
7-8% bone necrosis
When combining chemotherapy with RT for the treatment of OMM, what drug has been shown to be effective and how did it affect prognosis?
Temozolamide: 60mg/m2 x 5 days then q1 month
RT: 6 Gy x 5
Dogs tx with TMZ had a longer TTP vs RT alone; 205d vs 110d
No difference in ORR or MST
Dogs with OMM of what tumor volume are more likely to achieve a CR and longer MST when treated with RT?
<5cm3
Dogs with OMM have elevated ____ plasma values when compared to normal dogs.
What are 2 ways this can affect prognosis in dogs when treated with RT?
VEGF; shorter TTP and MST
Expression of ___ by tumor infiltrating lymphocytes has been documented in dogs with OMM. In what other tumors has this been documented (5)?
PD-L1
Also in OSA, HSA, MCT, CMT, prostatic ACA
A mutation in the KIT gene has been detected in exon ___ in ___% of dogs with MM.
All samples with a mutation were KIT+ on IHC, but what was the difference in staining?
How does the mutation affect prognosis?
Exon 11, C -> T mutation
10% of dogs with MM
Strongly positive in 56%
Weakly positive in 44%
Significantly associated with dz recurrence
How does the Oncept melanoma vaccine work?
In what % of dogs is a cell-mediated immune response produced?
Encodes human tyrosinase gene, which is inserted into pING plasmid vector.
Plasmid vector contains cytomegalovirus promoter, kanamycin resistance selection marker, and a CpG sequence (which signals through TLR9).
Tumor Ag is taken up by DCs -> presented via MHC class II (less commonly, class I) -> incites cell-mediated immune response in ~1/3 of dogs -> production of Ag-specific IFN-y T-cells
CpG sequences also augment TH1 response
What is the overall MST in dogs with stage I-III OMM and either adequate or inadequate locoregional control when treated with all available xenogenic vaccines?
Adequate locoregional control > 3yrs
Inadequate locoregional control 18m
