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Onco boards 2024 > tumor specific 25% LC > Flashcards

tumor specific 25% LC Flashcards

1
Q

what is the only fda approved veterinary therapy that is adaptive and specific ?

A

xenogenic DNA vaccine
- oncept

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2
Q

Most common loss of heterozygosity ?

A

mutations in tumor suppressor genes - p53

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3
Q

examples of loss of heterozygosity mutations

A

p53
PTCH
BRAF (human melanoma)
loss of INK4a (familial cut melanoma)

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4
Q

common locations of melanoma

A
  • digital, nail bed, foot padn- dog
  • haired skin
  • oral cavity
  • GI tract
  • eye,
  • nasal cavity
  • anal sac
  • mucocutaneous junctions
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5
Q

Oral melanoma, should you remove unilateral LN vs both LN vs no literature to support removing LN ?

A

histologic examination of the LN is recommended either through excision of the major LNs of the head and neck or sentinel LN (SLN) mapping

Selective lymphadenectomy avoids the indiscriminate extirpation of multiple LNs and, because it is a less extensive surgical dissection, reduces the risk of postoperative complications

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6
Q

equine melanoma treated with doxorubicin response rate

A

25% CR
ORR 47%

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7
Q

location of metastatic melanomas

A

lymph nodes, lungs, liver, meniges, adrenal gland

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8
Q

most common oral malignancy in the dog and common locations

A

melanoma
gingiva, lips, tongue, and hard pal- ate

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9
Q

oral melanoma common breeds

A

goldens, scottish terriers, chow chows, poodles, dachshunds

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10
Q

differentials for oral tumors

A

melanoma, squamous cell carcinoma, fibrosarcoma, osteosarcoma, acanthomatous ameloblastoma, and peripheral odontogenic fibroma

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11
Q

melanoma ihc cocktail

A

PNL2, Melan A, S100, tyrosinase, vimentin

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12
Q

BRAF mutations are common in human UV induced melanoma are they common in dog oral melanoma

A

no but they do have downstream ERK constituative activation

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13
Q

melanoma- associated genes clustered in the areas related to what pathways and processes

A

focal adhesion and PI3K-Akt signaling pathways, extracellular matrix–receptor interactions, and protein digestion and absorption

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14
Q

a small subset of dogs with malignant melanoma have mutations in what gene at what exon

A

c-kit exon 11

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15
Q

biologic behavior of haired skin melanoma

A

benign
surgery is curative with clean margins

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16
Q

What kind of vaccine is the k9 melanoma vax ONCEPT?

A

Xenogenic plasmid with human tyrosinase

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17
Q

What are prognostic factors for digit/nailbed tumors?

A

High stage regardless histo
distant mets in melanoma

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18
Q

Tx and survival times for digit/nailbed SCC?

A

Dog with sx good 2yr 40% and subungal better with 2yr 75%,

Cat 73days-30wk
2.5 mths - 7.5 mths

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19
Q

Tx and survival for digit melanoma? stage 1

A

Amp MST 12 months 1yr survivial ~ 50%
2 yr survival 12%
sx+Vax MST 476 days (16mths)

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20
Q

digital melanoma metastasis at diagnosis

A

30 - 40 %

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21
Q

how do dogs with digital melanoma die from their disease

A

distant or local mets

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22
Q

What are some molecular pathways that are mutated/changed with melanoma?

A

C-erb2, c-myc, BRAF(human), VEGF, β catnenin

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23
Q

What are prognositic factors for skin melanoma?

A

Histology, mitotic, location, breed, DNA ploidy, proliferation, lymphatic invasion

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24
Q

What are prognostic factors for oral melanoma?

A

Mitotic, size, stage, mets, bone lysis, location

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25
Q

What is the survival time with oral melanoma based on stage treated with surgery ?

A

Stage 1 (<2 cm no mets)- 12 - 30 months,
stage 2 (2-4cm no mets)- 5 - 27 months,
stage 3- (>4 cm +/- LN mets) 5 - 7 months
Stage 4 (distant mets) 80 days

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26
Q

dogs with stage I oral melanoma treated with standardized therapies, including surgery, RT, and/or chemotherapy, have an MST of approximately

A

12-14 mths
dogs die of distant mets not local recurrence

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27
Q

stage 1 oral melanoms PFS

A

19 months

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28
Q

melanoma staging

A

TNM WHO staging

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29
Q

in melanoma what % of LN are metastatic that are normal in size? big in size?

A

LN metastasis is present in approximately 70% of dogs with lymphadenomegaly
mets in approximately 40% with normal sized LNs.

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30
Q

what is an advance novel staging modality that may show melanoma mets

A

gallium citrate scintigraphy
CT

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31
Q

surgical margins for cutaneous melanomas

A

1 cm and 1 fascial plane deep

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32
Q

malignant melanomas surgical margins

A

2-3 cm wide and one fascial plane deep - underlying bone resection encouraged
or follow with RT

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33
Q

oral melanoma prognosis without complete excision

A

65 days
Dogs with incomplete histologic excision are 3.6 times more likely to die of tumor-related causes compared with dogs with complete histologic excision

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34
Q

melanoma behind premolar 3 were how much more likely to cause death (as opposed to rostral tumors)

A

4.3 times more likely to cause tumor related death

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35
Q

mst oral melanoma no sx

A

65 days - 2 mths

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36
Q

How does the melanoma vaccine Oncept work?

A

Human tyrosinase expressed on melanocytes causes Ab & Tcell response, same species do not generate enough response but xenogenic overcomes self tolerance
dendritic

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37
Q

What is survival in CMM with vaccine?

A

Stage 2-3 locoregional control 569 days. (19 mths)

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38
Q

What is unique about melanoma and RT?

A

Melanoma low a/B so hypofractionated or course fx better than small dose/fx

Low α/β ratio, or increased sensitivity to large fraction size 5-9 gy ( more acute tox less late tox)

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39
Q

melanoma response to RT?

A

Yes, 80-94% respond overall
25 - 70% cr
20 - 70% PR

recent study 0% response, 73% stable

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40
Q

pfs with rt for canine melanomas

A

PFS 4-8 months

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41
Q

How does RT+carbo work for melanoma?

A

Carbo thought to sensitize but differing results on if it helps, more AE with combo

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42
Q

What are the most common eye tumors in cats and dogs?

A

Dog conjunctiva melanoma
Cat anterior uveal melanoma

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43
Q

What are risk factors for developing ocular tumors?

A

UV, trauma

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44
Q

What ocular tumor are blue-eyed dogs at risk for developing?

A

Spindle cell sarcoma

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45
Q

What ocular tumors have the highest metastatic rate?

A

cat uveal intraocular melanoma and orbital tumors
melanoma mets but very slowly

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46
Q

local recurrence rate after rt in microscopic dz setting (melanoma)

A

26%

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47
Q

local recurrence rate after rt in macroscopic dz setting (melanoma)

A

45%

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48
Q

MST for dogs treated with RT with melanomas

A

4.5 - 15 months

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49
Q

RT protocols for melanoma

A

8 Gy x 4 (32Gy)
6 Gy x 6 (36 Gy)

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50
Q

cats treated with rt with oral melanoma mst

A

146 d (~5 mo)
one complete response
two partial response

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51
Q

dog with t1 or t2 melanoma treated with carbo radiosensitization 6gy x 6
recurrence rate
tt mets
mst

A

15% recurrence
10.2 months till mets
mst 12 months

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52
Q

dogs with oral melanoma treated with surgery and carboplatin
pfs
mst
when rt added?
recurrence rate?

A

overall median PFS (259 days - 9 mth)
MST (440 days - 15mth)
- did not significantly change when RT was added to the treatment protocol
- proportion of dogs with local recurrence was lower in the RT group (27%) compared with dogs not treated with RT (67%)

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53
Q

malignant melanoma in oral and non oral sites treated with RT vs RT + temozolamide
ORR
TTP
MST

A

ORR not sig diff - 81-87%
TTP - 205 d (6.8 mo) with RT+ temo vs 110 (3.5 mo) with RT only
MST not stat sig - 192 d (6.4 mo) vs 402 d (13 mo)

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54
Q

rt and melanoma tumor size MST

A

size <5cm3 86 weeks- 22 mths
5-15 cm3 16 wks - 4 mths
> 15 cm3 21 wks - 5 mths

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55
Q

RT and melanoma and VEGF

A

dogs with higher plasma VEGF levels treated with hypofractionated protocols had a shorter time to treatment failure and a shorter MST

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56
Q

RR for gross melanomas treated with:
cisplatin/piroxicam
carbo
chemo in general

A
  • 18%
  • 28%
    five retrospective studies investigating the role of chemotherapy in the adjuvant set- ting after either surgery or RT found no significant differences in outcomes with the addition of chemotherapy to the treatment protocol
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57
Q

result of oncept trials

A

(1) is safe
(2) leads to the development of antityrosinase antibodies and T cells (3) is potentially therapeutic
(4) is an attractive candidate for further evaluation in an adjuvant, minimal residual disease phase II setting for canine MM

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58
Q

stage 3 and 4 melanoma treated with masitinib
MST
AE
success

A

MST 119d - 4 mth
low grade ae in all dogs - anemia diarrhea and anorexia
not good as single agent

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59
Q

microRNA expression in
CMM
OMM

A

CMM - decreased in some and increased in others
OMM - downregualted

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60
Q

checkpoint expression in melanomas vs melanocytomas

A

PD1/PDL1 sig higher in melanoma

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61
Q

can endotracheal intubation cause seeding of OMM

A

Suspected Iatrogenic Seeding of Oral Melanoma Secondary to Endotracheal Intubation in a Dog

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62
Q

pleural effusion reportedly melanocytic

A

following incomplete mm removal in a dog

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63
Q

Correlation Between KIT Expression and c-Kit Mutations in 2 Subtypes of Canine Oral Melanocytic Neoplasm

A

No relationship between c-Kit mutations and KIT expression
This DOES NOT support the used of c-kit targeting therapies

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64
Q

tumor infiltrating lymphocytes in oral melanoma

A

longer survial associated with higher TIL scores and higher CD8+ lymphs
lower CD4+/CD25+/FoxP3+Tregs

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65
Q

tumor size as a predictor of lymphatic invasion in omm

A

tumors <6.5mm (<0.6 cm) had no lymphatic invasion with 100% sn
tumors >24.5 mm (>2.4 cm) had guarantee of lymphatic invasion of 100% sp

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66
Q

expression of cyclin D1, Ki67 in omm

A

Cyclin D1 was detected in 69%
Ki-67 was present in 88.5%

cyclin d1 may be a marker of prognosis

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67
Q

somatic focal amplification on chromocome 30 Canis Familiaris [CFA] associated with what type of melanoma

A

amelanotic omm
linked to poor prognosis

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68
Q

prognostic factors for omm

A

gingival location MUTLIPLE STUDIES, lymphadenomegally, tumor ulceration, >6 mf

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69
Q

Important draining LN in OMM according to Javma study
frequency of LN mets in a OMM
frequency of contralateral ln

A

37% LN in omm
MRLN 81% (18% of these did not have mand ln)
23% contralateral

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70
Q

Evaluation of prognostic impact of pre-treatment neutrophil to lymphocyte and lymphocyte to monocyte ratios in dogs with oral malignant melanoma treated with surgery and adjuvant CSPG4-antigen electrovaccination

A

No sig associated between leukocyte ratios and outcome

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71
Q

Evaluation of accuracy for 18F-FDG positron emission tomography and computed tomography for detection of lymph node metastasis in canine oral malignant melanoma

A

CT clinical grading sens 83%, spec 94%
PET techniques 100% sens but requires SUV (standard uptake value) standardization to be specific

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72
Q

Difference in outcome DFI and ost between curative intent vs marginal excision as a first treatment in dogs with oral malignant melanoma and the impact of adjuvant CSPG4-DNA electrovaccination

A

DFI sig shorter in dogs with marginal excision over curative intent (6 mths vs 8 th) but not sig. on OST

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73
Q

Chondroitin sulphate proteoglycan 4 [CSPG4]

A

cellular membrane Ag overexpressed in canine melanoma cells (57%)
early cell surface progression marker involved in tumor cell proliferation, migration and invasion

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74
Q

bone invasion impact on ost for omm

A

Dogs with bone invasion was sig shorter than without 397 d (13 mth) vs 1063 d (35 mth)
worse ost with high Ki67 and MC >4

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75
Q

pfs and ost in gross omm treated with 36gy

A

pfs 171 d - 6mth
ost 232 d - 8 mth
improved if low WHO stage (I/II) and irradiating subclinical disease

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76
Q

omm and phagocytic activity

A

Canine oral primary melanoma cells exhibit shift to mesenchymal phenotype and phagocytic behavior which may play a role in progression

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77
Q

CD146 expression on OMM

A

expressed on on primary melanoma cells
maybe be a prognostic marker

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78
Q

Long-term survival of dogs with stage 4 oral malignant melanoma treated with anti-canine PD-1 therapeutic antibody

A

pulmonary nodules regressed
local tumro control
2 dogs

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79
Q

what is the effect of FOXP3, CD3, and IDO on cutaneous melanomas

A

Increased risk of tumor related death with increased FoxP3 cells per HPF and CD3+ cells that were FoxP3+ surrounding the tumor, and IDO+/HPF

IDO+/HPF independent prognostic factor

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80
Q

metastatic rate of foot pad melanoma

A

55%

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81
Q

outcome of food pad melanoma treated with surgery +/- adjuvant therapy

A

PFI 101 d (3.5 mth)
MST 240 d (8 mth)

adjuvant therapy did not improve outcome

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82
Q

TIL in feline mnelanocytic tumorts

A

TIL increased with MC and cellular pleomorphism

TIL Inversely associated with positive melan A PNL2 staining cells

TIL may be associated with features of malignancy

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83
Q

nasal planum melanocytic tumors in cats predisposing factor

A

pigmentation

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84
Q

nasal planum melanocytic tumors in cats MST

A

265d (9 mth)
LN mets in one
short term remission acheived with rt

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85
Q

is circulating cell free dna in cats with diffuse iris melanoma useful

A

not a good markers even if mets

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86
Q

non ocular melanomas in cats prognostic factors

A

tumor site ( lips, oral, nasal, mucosa, nasal planum )
MC >4
intratumoral necrosis

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87
Q

grading of non ocular melanomas in cats
SN and SP of the scheme

A

high grade if aggressive location and one of these: mc>4, intratumoral necrosis present
high grade if other location and both MC>4 and necrosis
80% sensitivity, 92% specificity for predicting tumor related death

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88
Q

MST of non ocular melanomas in cats

A

MST high grade 90 days
MST low grade not reached

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89
Q

TIL and prognostic factors in canine melanoma

A

CD20+ TILS sig associated with MI, pleomorphism, and pigmentation as well as tumor related death, presence of mets/recurrence, shorter OST and DFI

high CD20 is neg prog indicator

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90
Q

pevonedistat is a selective NEDD8 activating enzyme (NAE) inhbitor. what is its affect on malignant melanoma cells

A

Pevonedistat sig reduced viability of cells in dose and time dependent manner.
Promotes apoptosis and inhibits growth through DNA re-replication and cell senescence
- Some cell lines resistant
- P21 levels increased in more sensitive lines

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91
Q

COX 2 expression in cutaneous melanomas

A

over expressed in 42% OF CMM

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92
Q

cox 2 expression in oral mm

A

over expressed in 34% of omm

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93
Q

Histone demethylase inhibitors may be a potential therapeutic strategy for OMM. may decrease resistance to what chemotherapeutics

A

platinum agents

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94
Q

JARID1B

A

histone demethylase that causes proliferation dormancy and decreases drug sensitivity

highly expressed in canine melanomas

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95
Q

Antitumour effects of Liporaxel (oral paclitaxel) for canine melanoma

A

Induced anti angiogenesis - CD31 antibody on ihc
Induced apoptosis - terminal deoxynucleotidyl transferase dUTP Nick End labeling assay (TUNEL)

Down regulated cyclin d1 and inhibited cell proliferation - western blot

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96
Q

what cbc findings might you see in a cat with an intestinal mast cell tumor

A

anemia from perforation
commonly have mastocytosis and eosinophils

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97
Q

when combining vinblastine and palladia for mast cell tumor treatment what is recommended in terms of dosing and why

A

1.6 mg/m2 vinb - 20% dose reduction from low end 50% dose reduction from high end
palladia 3.25 mg/kg (2.75 in a later paper)

neutropenia is DLT

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98
Q

What do mast cells contain?

A

Histamine, heparin, vasoactive amines, prostagladinD, proteolytic enzymes

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99
Q

What other disease in dog have mast cells in periphery?

A

Parvo, skin diz, trauma, other neoplasia

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100
Q

breeds commonly affected by MCT

A

mbd, boxer, Bos- ton terrier, English bulldog, pug, Labrador and golden retrievers, cocker spaniels, schnauzers, Staffordshire terriers, beagles, Rhode- sian ridgebacks, Weimaraners, and Chinese shar-pei

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101
Q

genes identified in Goldens with MCT

A

GNAI2 gene and multiple genes associated with hyaluronic acid synthesis may be risk factors for MCT development

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102
Q

how do MCT in young animals behave

A

can spontaneously regress
described in cats, pigs, horse, and humans
one report of multiple mct regressing in jack Russel

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103
Q

is there a cause of MCT

A

thought to be chronic inflammation or skin irritants

Chromosomal fragile site expression, a phenomenon thought to genetically predispose humans to develop certain tumors, was shown to be increased in boxer dogs with MCT

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104
Q

VEGFR2 activation and mct

A

vegf expression has bee shown in many mct

preliminary evidence that VEGFR2 activation may be associated with inferior post surgical outcomes

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105
Q

Which breeds have benign MCT?

A

boxer, pug, bulldog, goldens in one study

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106
Q

Which breeds have malignant MCT?

A

GR, mastiff, Shar-pei, rottweiler, Shih Tzu, frenchie, pit bull

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107
Q

Survival of gastric MCT?

A

10% @ <6months

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108
Q

Are multiple cutaneous MCT worse or better? What stage?

A

Stage3, Don’t know if de novo but one study MST not reached

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109
Q

What are the metastatic rates with grade in MCT?

A

Grade1 <10%,
grd2 5-22%,
grd3 55-96%

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110
Q

What is the survival with mets to liver, spleen, abdominal Ln for MCT?

A

34 days

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111
Q

What is the metastatic rate of SQ MCT?

A

6%

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112
Q

Prognostic factors for MCT?

A

Grade, proliferation, size (own , ckit, location, stage(1vs. 3)

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113
Q

What is survival with MI in MCT?

A

MC <5 MST 70months 5.8 yrs
MC >5 MST 2 months regardless of grade

vs

MC < 7 MST >2 YEARS low grade
MC >7 MST < 4 mth high grade

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114
Q

What is survival with Grade 2 MCT Ki67 >1.8

A

1yr survival 43%
2yr survival 21%

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115
Q

What locations have been associated with decreased survival for mct?

A

Mucocutaneous, nailbed, inguinal/peringuinal

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116
Q

Is inguinal truly worse for mct location?

A

Not in one study but preputial/scrotal MST 4.2months

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117
Q

What is the survival of oral/perioral mct?

A

MST 52months that decrease to 14months if mets

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118
Q

What is the survival of muzzle mct?
what % have mets at dx

A

MST 30 months, with 46% with mets @dx

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119
Q

What % of pathologist agreed on grade 1-2 patnick MCT?

A

<64%

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120
Q

What characteristics are evaluated for 2-tier MCT grading?

A

Mc, bizarre nuclei, multinucleated cells, karomegaly

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121
Q

What is the % recurrence with incomplete margins mct ?

A

25-30% especially grade 2

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122
Q

What is the survival with 2-tier MCT grading?

A

Low >2yr
High 4months

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123
Q

What is the survival with grade3 sx alone?

A

MST 9months, recurrence 50-60%

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124
Q

What is rr of palladia with RT for gross MCT?

A

ORR 76.4%
MST not reached

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125
Q

what is rr of pred with rt for gross mct?

A

ORR 88.5%
PFS 1031days(34 mo. 2.8yr)

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126
Q

Survival times for grade3 MCT sx with vinblastin/pred?

A

MST 1374 days (45 mo, 3 yr), another not reached

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127
Q

What is the response with pred/vinblastine in gross MCT?

A

rr 47%
MST 154days
grd3 MST 134days

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128
Q

What is the % response with vincristine and vinorelbine with gross MCT?

A

Vinc 7%, vinorelbine 13%

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129
Q

What is the response with CCNU with MCT sx removed?

A

42%

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130
Q

What are the responses of mct with hydroxyurea and chlorambucil?

A

Hydroxy-28%,
Chloram-38%

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131
Q

What is the survival with bone marrow mets in MCT?

A

With CCNU MST 43 days, symptomatic ~30days

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132
Q

What is the MST with grade 3 met with mets?

A

194 day(6 mo) vs. 503 (16 mo) if no mets

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133
Q

What is the MST with grade3 mct with Ln mets and tx/

A

240 days (8 mo) with tx and 42d if no tx

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134
Q

What is the survival with SQ MCT?

A

With incomplete margins MST 1199days (~40 mo, ~3 yr)

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135
Q

What feline breed is associated with a better prognosis with MCT?

A

Siamese, usually younger and develop histiocytic form

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136
Q

Where is MCT diz located in cats?

A

More visceral, GI and generally do not have cutaneous lesion associated (unlike dogs)

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137
Q

What other disease cause circulating mast cells in cats?

A

None, generally just MCT; 50% splenic have in BM

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138
Q

What is the tx and survival for splenic MCT in cats?

A

splenectomy even if distant mets can do well MST 12-19months, chemo unknown

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139
Q

Tx and prognosis with cutaneous MCT in cats?

A

Surgery with smaller margins because most benign, Histiocytic “wait & see’

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140
Q

Tx and survival with GI MCT in cats?

A

Surgery need large margins, most succumb to diz quickly

less than 1 year

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141
Q

What is sclerosing GI MCT in cats?

A

New GI variant, 23/25 cats dead in 2 months

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142
Q

What are the different histologic forms of MCT in the cat?

A

Histiocytic (spontaneously resolves); Mastocytic-compact (benign),
Diffuse (anaplastic malignant)

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143
Q

Patnaik grading scheme

A

Gr 1 - 3
looking at depth of invasion, cellular atypic, granularity, nuclear feature, MC, and multi nucleation

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144
Q

Kiupel grading scheme

A

high or low

HIGH =
MC >7/10hpf ,
>3 cells with multi nucleation/10hpf ,
>3 bizarre nuclei/hpf ,
karyomegaly >10% of cells

MC <7 low grade

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145
Q

bostock mct grading scheme

A

opposite of patnaik

gr I = anaplastic undifferentiated - highly cellular irregular size and shaped of nuclei, frequent mitosis, few granules

gr ii = intermediate grade, closely packed cells with indistinct cell borders, lower n:c ratio compare to anaplastic, infrequent mitosis, more granules than anaplastic

grIII = clearly defined cell boundaries, well differentiated, spherical or oval nuclei, rare or absent mitosis, large deep staining granules

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146
Q

based on a consensus statement and a study comparing the 2 and 3 category mct grading schemes what recommendation can be made about staging low grade tumors

A

staging should be recommended regardless of grade to local LN but full staging may not be necessary for low grade tumors

15% of Kiupel low grade tumors had more aggressive behavior

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147
Q

based on mct consensus statement what is the preferred mct grading scheme

A

kiupel + Ki67 & AgNOR
- help you understand low grade tumors risk of local recurrence

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148
Q

WHO staging scheme of mct

A

0 = one tumor incompletely excised form the dermis identified histologically without regional ln involvement
a - without signs
b - with systemic signs
1 = one tumor confined to the dermis without regional LN involvement
a - without signs
b - with systemic signs
2 = one tumor confined to the dermis with regional ln involvement
a - without signs
b - with systemic signs
3 = multiple dermal tumors, large infiltrating tumors with or without regional Ln involvement
a - without signs
b - with systemic signs
4 = any tumor with distant metastasis including bone marrow

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149
Q

proposed staging from consensus

A

Stage I Single tumor, without regional lymph node involvement
Stage II Multiple tumors (≥3), without regional lymph node involvement
Stage III Single tumor, with regional lymph node involvement
Stage IV Large and infiltrative tumors, without delineation, or multiple
tumors (≥3), with regional lymph node involvement
Stage V Any tumor with distant metastasis, including bone marrow invasion
and the presence of mast cells in the peripheral blood

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150
Q

dog with multiple cutaneous tumors - what stage and how does it affect prognosis?

A

stage 3 for WHO or 4 on new staging

Several studies indicate that there is no difference in outcome between patients with a single cutaneous MCTs and those with multiple MCT

others have suggested an inferior outcome in dogs with multiple tumors

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151
Q

dog with dermal mct and regional Ln metastasis what stage and how does it affect prognosis ?

A

stage 2 for WHO and stage 3 for new scheme

In 3 studies, the presence of MCs in the regional LNs was a negative prognostic factor for disease-free interval (DFI) and survival

however
Other studies have shown that dogs with intermediately differentiated MCTs with LN metastasis may have a good prognosis if the affected LN is removed and adjuvant chemotherapy and/or RT is administered.

grade seems more impt for outcome

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152
Q

histologic grading scheme of mct metastatic lymph nodes

A

HN0 = not metastatic, None to rare (0-3), scattered, individualized mast cells in sinuses (subcapsular, paracortical or medullary) and/or parenchyma per field
HN1= Pre Metastatic, Greater than three individualized mast cells in sinuses (subcapsular, paracortical or medullary)
and/or parenchyma in a minimum of 4 fields
HN2 = early metastatic, Aggregates of mast cells (>3 associated cells) in sinuses (subcapsular, paracortical or medullary) and/or parenchymal, or sinusoidal sheets of mast cells
HN3 = overtly metastatic, Disruption or effacement of normal nodal architecture by discrete foci, nodules, sheets, or overt masses composed of mast cells

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153
Q

dfi and ST for HN0/1 tumors

A

DFI for those classified as HN0/1 was not reached
MST was 1,824 days = 5 yrs

The 2-year disease-free percentages and survival percentages were 90% for HN0/1

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154
Q

dfi and st for HN2/3 tumors

A

DFI was not reached
MST was 804 days = 27 mths

The 2-year disease-free percentages and survival percentages were 56% for HN2/3.

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155
Q

MST for poorly differentiated tumors with LN mets vs no LN mets

what happens to ST if you treat the LN

A

high grade Ln mets ST = 194 d = 6.5. mth
high grade NO LN mets ST = 503 d =17 mths

treatment of the LN improved MST (240 days = 8 mth) compared with those dogs whose LNs were not treated (42 days)

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156
Q

how does the biologic behavior of a mct affect outcome

A

recent rapid progression is a worse outcome

local tumor ulceration, erythema, or pruritus have worse prognosis

recurrence after surgery is a worse prognosis

** all shown in few studies - not definitive**

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157
Q

Comparison of histologic margin status in low-grade cutaneous and subcutaneous canine mast cell tumours examined by radial and tangential sections

A

Radial sections: 4 radial sections of 5 directions (cr, cd, d, v, and deep) to inked margins
Tangential sections: taken parallel to the ink edge covering great % of total margin surface area

Tangential sections detect sig. More incomplete surgical margins
** 23% are categorized as neg on radial that were pos on tangential sectioning**

Radial sections incorrectly called clean – 50% of margins

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158
Q

when to use radial versus tangential mct margins

A

Radial sections have 100% specificity of predicting negative tangential margins at a cut point of 10.9 mm

if margins <10.9 mm tangential sectioning should be used

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159
Q

Amount of skin shrinkage affecting tumor versus grossly normal marginal skin of dogs for cutaneous mast cell tumors excised with curative intent

A

17.7% shrinkage with tumor shrinkage (4.45%) < normal skin shrinkage (24.42%)

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160
Q

Equation created to estimate post excisional margins from pre excisional measurements for mct

A

18.4%
(pre- excisional margin = postformalin margin/0.244)

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161
Q

compared to intra op how much did the length of surgical margins decrease at each processing step?

for mct
for sts

A

Compared to intra op measurements the length of surgical margins decreased at each processing step by median of

  • 3 mm post op, 5 mm post fix, and 8.8 mm on glass/HTFM for MCT
  • 2.5 mm, 2 mm, and 5 mm for STS

Max reduction in the total length of margins was 29.6 mm for MCT and 24.2 mm for STS

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162
Q

prognostic factors for mct

A

grade
stage
location
Proliferation - MC, AgNOR, Ki67
growth rate
microvessel density
recurrence
systemic signs
age
breed
sex f>m
tumor size
c-kit mutation - worse
DNA copy number

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163
Q

how does micro vessel density affect prognosis for mct

A

increased MVD = higher grade, higher degree of invasiveness and worse prognosis

164
Q

what is AgNOR

A

histo silver staining method to identify generation time - speed of cell cycle progression proliferation rate

low for G1 phase and high for S-G2 phase

165
Q

what is Ki67

A

ihc method to identify growth fraction - actively dividing cells

seen during mitosis - during interphase the non-phosphorylated form of Ki-67 form complex with DNA - role in organization of nucleolar chromatin in proliferating cells

166
Q

what is Ag67

A

AgNOR x Ki67

growth fraction and proliferation rate

167
Q

MC < 7 ( low grade mct)
MST
risk of death
risk of new tumors

A

mst > 2 years
5% dogs died due to mct disease
20% developed new tumors

168
Q

MC > 7 ( low grade mct)
MST
risk of death
risk of mets

A

MST ,4 mths
90% dogs died due to mct
70% developed mets

169
Q

risk of recurrence based on grade
Gr I and II mct

A

Tumors measuring < 3.2 cm excised with microscopic lateral margins at least 1 cm and a deep margins at least 4 mm including a fascial layer did not recur

170
Q

risk of recurrence based on grade
low grade mct

A

96% of tumors did not recur, even though 29% were excised with microscopic margins
of 3 mm or less

171
Q

risk of recurrence based on grade
high grade mct

A

36% recur locally despite histologically tumor-free margins

172
Q

how does AgNOR score affect outcome of mct

A

Average AgNORs per cell < 1.7: No dogs died due to MCT-associated disease

** Average AgNORs per cell > 2.25**: Significantly decreased survival

Average AgNORs per cell > 4: Significantly decreased survival:
– 66.7% of dogs died from MCT-associated disease – MST 4 mth

173
Q

Low Ki67 index and recurrence rate of mct

A

ki67 <23 - 11% recurrence

174
Q

high ki67 and recurrence rate of mct

A

ki67 >23
increased risk of recurrence and mets

175
Q

Ag67 and mct recurrence

A

Ag67 >54 - significantly associated with an increase rate of mct recurrence, increased risk of MCT-related mortality and
metastasis
60% 1 year survival

low grade tumors Ag67 < 54 - 11% recurrence rate

low grade tumor Ag67 > 54 increased risk of recurrence

176
Q

KIT pattern I - perimembranous
local rr
distant met rate
mortality

A

2.4% local rr
14.3% distant met rate
2.4% mortality rate

177
Q

KIT pattern ii - focal stippled
local rr
distant met rate
mortality

A

14% local rr
31% distant met rate
25.6% mortality

178
Q

KIT pattern III - diffuse cytoplasmic
local rr
distant met rate
mortality

A

23.1% local rr
38.5% rate of distant met
38.5% mortality

sig dec dfi and st compared to pattern 2

179
Q

C kit exon 8 and mct tx

A

tend to be lower grade tumors
mutation in exon 8 of c-Kit are also expected to respond to TKIs

180
Q

c kit exon 11 and mct tx

A

associated with higher grade - high rate of metastasis and mortality and recurrence
will respond to TKIs

181
Q

SQ mct - MC
risk of recurrence
risk of death

A

MC>0 <4 compared to MC 0
5.59 times higher risk of local recurrence
3.72 time higher risk of death

MC>4 compared to MC 0
36 times higher rate of mct related death
130 times higher risk of local recurrence
increased risk of metastasis

182
Q

SQ MCT – Infiltrative tumor, MC > 4

effect of multinucleation on mst

A

MST 140 days 4.6 mths vs MST 950 days 32 mths with no multi nucleation

183
Q

SQ MCT and growth pattern

A

infiltrative tumors are more likely to recur locally, cause distant mets, and have distant mct development

in general, completely excised well-circumscribed SCMCTs are unlikely to recur

184
Q

infiltrative SQ MCT time to recurrence

A

Incompletely excised SCMCTs with infiltrative pattern: 70 days
Completely excised SCMCTs with infiltrative pattern: 1,000 days (33 mo)
Incompletely excised well-circumscribed SCMCTs: 365 days

185
Q

AgNor for SQ MCT

A

agnor >2.71 sig more likely to reoccur

186
Q

ki67 for SQ mct

A

ki67 >21.8 high risk of mets

187
Q

Ag67 for SQ mct

A

Ag67 >55 associated with increased risk of mct related mortality and metastasis

188
Q

KIT pattern 3 SQ MCT

A

Increased odds of local recurrence and
developing metastasis compared to
pattern I
– Increased odds of local recurrence
compared patterns I and II

189
Q

is c-kit associated with high or low grade mct

A

c-kit mutations appear to be associated with 25% to 30% of intermediate- and high-grade MCTs, and evidence suggests that they are linked to increased risk of local recurrence, metastasis, and a worse prognosis

190
Q

mct are the most common cutaneous tumor of the dogs

A

16 - 21 %

191
Q

what percent of dogs have multiple SQ or dermal mct

A

11- 14%

192
Q

what is the distribution on the body of cmct

A

50% of cutaneous MCTs occur on the trunk and perineal region, 40% on the limbs, and 10% on the head and neck

193
Q

dariers sign

A

erythema and wheal formation in surrounding tissues

194
Q

what percent of dogs with mct have gi ulceration

A

35-83% of dogs that underwent necropsy

195
Q

systemic signs of mct

A

vomiting, diarrhea, fever, peripheral edema, and rarely collapse.

196
Q

risk of surgery to mct

A

life-threatening hypotensive events during surgery - prostaglandins in the D series secreted by tumor cells

Coagulation abnormalities and localized excessive bleeding

197
Q

Metastatic rates for undifferentiated MCT

A

range from 55% to 96%, and most dogs with these tumors die of their disease within 1 year

198
Q

how does anatomic location affect dermal mct

A

perigenital, perioral, mucocutaneous junction - higher grade, higher, met potential, and shorter survival

199
Q

response to pred alone for cmct

A

20% ORR

4% cr
16% pr

200
Q

what stain do you add to cyto to reveal granules in mct

A

wright giemsa or toluene blue

may still be agranular

201
Q

ihc for mct

A

vimentin - , CD117 (KIT) +, chymase +, tryptase +, mcp-1+/- , IL8 +/-1

202
Q

what can cause mastocytosis in the Buffy coat

A

acute inflammatory disease (in particular parvoviral infections), inflammatory skin disease, regenerative anemias, neoplasia other than MCT, and trauma

One study revealed that peripheral mastocytosis is actually more likely to occur and may be more dramatic in dogs with diseases other than MCT - dont perform anymore

203
Q

incidence of BM infiltration of cMCT at dx

A

incidence of bone marrow infiltration at initial staging was only 2.8%

involvement of bone marrow or peripheral blood in the absence of disease in regional LN or abdominal organs is unlikely and the routine performance of bone marrow aspirates for clinical staging has fallen out of favor

204
Q

incidence of BM infiltration of visceral MCT at dx

A

56% of bone marrow aspirates reveal MC dissemination

205
Q

response of cmct to vincristine

A

ORR 7% - PR only

206
Q

response of cmct to CCNU

A

ORR 44%
6% CR
38% PR

response duration 79d

207
Q

response of cmct to vinblastine/pred

A

ORR 43%-47%
CR 4-33%
PR 13- 39%

response duration 154 days - not reached

208
Q

response of cmct to vinb/pre/cytoxan

A

ORR 63%
CR 18%
PR 45%

response duration 73 days

209
Q

response of cmct to COP-HU

A

ORR 59%
23% CR
35% PR

response 53 d duration

210
Q

response of cmct to CVP

A

ORR 57-64%
24-29% CR
32-35% PR

duration: 141d CR, 66d PR
1 year in another study

211
Q

response of cmct to hydroxyurea

A

ORR 28%
4% cr 24% pr

response duration 46 days

212
Q

response of cmct to pred/chlorambucil

A

ORR 38%
PR 46%
CR 14%

duration 533

213
Q

response of cmct to palladia

A

ORR 43-63%
PR 28-46%
CR 14-17%

duration 3 months - not reached

214
Q

response of cmct to masitinib (kinavet)

A

ORR 55-82%
PR 29 - 44%
CR 26-38%

duration not reached

215
Q

response of cmct to palladia and ccnu

A

orr 46%
pr 36%
cr 10%

216
Q

response of cmct to palladia and vinb

A

orr 71%
pr 57%
cr 14%

217
Q

on multivariate analysis which prognostic factors were significant

clinical stage, history of tumor recurrence, Patnaik and Kiupel grades, predominant organization of neoplastic cells, mitotic count, Ki-67 labeling index , KITr pattern, and c-KIT mutational status

A

new amended clinical staging system and tumor recurrence

all were significant on univariate analysis

218
Q

will c-kit mutation status predict response to treatment?

A

c‐kit mutation status did not predict treatment response

Palladia - 20% had Ckit - 46% RR
Vinb - 30% had ckit - 30% RR

PFS - 78 d VBL and 95.5d Palladia
OST - 241.5 d VBL and 159 Palladia
PFS and OST were not significant

219
Q

palladia, RT, and pred response of gross MCT, mst , pfi

A

24Gy in 3 or 4 fractions

ORR 76.4%,
CR 58.8%,
PR 17.6%

Median PFI 316 days(10 mo), MST not reached

220
Q

if a dog has high grade tumor should you remove draining lymph node

TTP
MST

A

time to progression is sig short in dogs without lymphadenectomy (150 days) compared to the other dogs (229 days)

MST was also shorter in dogs that did not undergo lymphadenectomy (250 days) compared to dogs that underwent lymphadenectomy (371 days)

On multivariable analysis, lack of lymphadenectomy was associated with higher risk of overall tumor progression, nodal progression and tumor-related death,

221
Q

what size mct tumor has been shown to have increased risk of recurrence

A

3 cm or >

222
Q

should you remove the local lymph nodes of mct regardless of staging

A

lack of immediate lymphadenectomy was associated with a higher risk for tumor progression

No significant difference in survival time

223
Q

metastatic rate of mucosal MCT

A

> 50%

224
Q

where do mct metastasize to in the cns

A

intramedullary

225
Q

dose limiting toxicity of palladia and vinb combo

A

neutropenia

226
Q

should you give palladia with vinb for mct

A

AG says no - 50% reduction in dose intensity compared to single agent

71% rr and enhanced myelosuppression suggest additive or synergistic activity

227
Q

prognostic factors for SQ tumors

A

MC >4, multi nucleation, absent granules, multiple mct

228
Q

what is the sn and sp of cytologic grading scheme

A

88% sn
94% sp

229
Q

prognostic factors for feline cMCT

A

MC >5 — MC >2 in another study
incomplete surgical resection - sig effects PFS
cytoplasmic KIT stain - sig effects OST
visceral location
poor differentiation

230
Q

prognostic indicators in cats undergoing splenectomy for splenic mct

A

Administration of a blood product, metastasis to a regional lymph node, and evidence of either concurrent or historical neoplasia were negatively associated with survival

Response to chemotherapy was associated with an improved median survival time

231
Q

ST in cat with mct with splenectomy

A

mst 390 days in one study

Splenectomy vs not (MST 856 vs 342d)

role of chemotherapy is unknown

232
Q

feline intestinal mast cell tumor prognostic factors

A

degree of differentiation, MC >2,

233
Q

outcome of treatment of feline GI mct
chemo alone
sx and chemo
steroids alone
sx and steroids

A

chemo alone - MST 541d
sx and chemo - MST 396d
steroids alone - MST 55d
sx and steroids - 340d

no significant difference to survival time between treatment groups
Any treatment improved survival times

234
Q

palladia use in cats for mct
clinical benefit
rr
AE

A

CB 80% visceral 86% cutaneous 76% gi
RR 70%
60% experienced adverse events with 87% defined as low Grade 1 or 2

235
Q

ckit mutation and prognosis for feline splenic mct

A

No correlation was observed between c-Kit mutations and tumour differentiation, mitotic activity or survival

236
Q

how frequently was kit staining in feline
cMCT
splenic MCT
GI MCT

A

69% of cutaneous MCTs,
35% of splenic MCTs,
33% of GI MCTs were positive for KIT

237
Q

superficial RT for cutaneous mct

A

limited case series
3 patients had cr
low grade tox

238
Q

what stain and sectioning technique was shown to have a 98% accuracy for identifying metastatic mct LN

A

evaluation of the first longitudinal section and an additional step section = 100% accuracy

200um step parallel to the first section

recommend metachromatic stain such as toludine blue

239
Q

what is the detection rate of sentinel ln mapping with CT lymphangiography

A

90% detection rate
9% failure rate

240
Q

based on CT lymphangiography how many tumors changed stage or treatemtn recommendation

A

40% of tumors had a change of stage or tx recommendation by using the snl not the lrln

241
Q

sentinel ln mapping with CT lymphangiography showed was disagreement with loco regional LN

A

27-32 % of sentinel LN were not the regional ln

242
Q

does the combination of RT with vinblastine cause and hematologic toxicity ?

A

does not increase the risk of neutropenia

243
Q

Mast cell tumours in dogs less than 12 months of age - prognosis

A

great - all alive at >1000 days despite 4 being high grade and 12 with mets

244
Q

Salivary miR-21 as a biomarker for mct

A

High in dogs with MCT compared to healthy group

245
Q

Recurrent gene mutations detected in canine mast cell tumours

A

Prevalence of GNB1 mutation 17.3% (similar to prevalence of KIT alterations)

GNB1 mutations did not affect survival negatively and tended toward positive

246
Q

pre op neoadjuvant vinblastine-prednisolone
use
complication rate
success of complete margins
recurrence rate

A

can be used for unresectable mct or to improve margins

16.7% wound dehiscence
complete excision 47%
local recurrence 21% - not influenced by completeness of excision or response to vinb

247
Q

Lymph node metastasis in feline cutaneous low-grade mast cell tumours

A

59% had early or overtly metastatic LN despite low grade

248
Q

ST gastrointestinal mct feline

A

one study showed st 531 d

sx, chemo, pred all aided st

249
Q

metastatic rate of mct to spleen/liver

A

overall met rate 10.7 %
10.2% to spleen
6.3% to the liver
5.9% to both

250
Q

if mct mets not identified in the spleen will it be found in the liver?

A

low likelihood in liver if not in the spleen
nef spleen ctyo has 99% ppv

251
Q

what has been associated with splenic mct metastasis in dogs

A

tumor size and systemic signs

252
Q

Τhe Effect of Opioid Administration on Cytologic and Histopathologic Diagnosis of Canine Cutaneous Mast Cell Tumors Treated by Surgical Excision

A

administration of morphine or butorphanol as part of the preanesthetic medication for surgical removal of canine cutaneous mast cell tumors does not influence histopathologic and cytologic grading of MCTs

253
Q

Inclusion of fibroblasts and collagen fibrils in the cytologic grading of canine cutaneous mast cell tumors

A

higher fibroblasts and/or collagen fibrils were associated with increased survival and low grade

254
Q

Wound formation, wound size, and progression of wound healing after intratumoral treatment of mast cell tumors in dogs with tigilanol tiglate

A

Maximal wound formation day 7 in 89% of dogs
Wounds left to heal by second intention
Time to heal was 28 - 42 days

wound formation correlates with effectiveness

255
Q

response rate of tigilanol tiglate

A

75% CR by 28 days with not recurrence in 93% by 84 days

88% CR after two treatments

256
Q

recurrence of mct after stelfonta

A

12 months

257
Q

metastasis with high grade mct location

A

LN mets 96%, spleen 67%, liver 59%, bone marrow 41%, kidneys 33%, heart 29%, lung uncommon 18%

258
Q

met rate of inguinal mct

A

40%

259
Q

met rate of multiple mct nodules

A

47%

260
Q

cyto grading overall accuracy

A

94%
sig associated with mst and tumor related death

261
Q

wound healing complication for marginal mct vs sts

A

29% for mct
31% for sts

262
Q

is it safe to use chemo post operatively after mct removal

A

Postop chemo </=30d associated with increased odds of incisional complications
steroids was not

263
Q

surgical margins for low grade mct

A

Conservative lateral margins <2cm for small tumors okay
>2 cm <3cm margins for larger tumors are okay for low grade MCT

264
Q

Outcomes of adjunctive radiation therapy for the treatment of mast cell tumors in dogs and assessment of toxicity

A

No SC MCT recurred after radiation therapy and only 7% of dogs with SCMCT were reported to have died of their disease

RR similar between radiation type 526 day

supports sue of rt after narrow or incomplete excision

265
Q

use of prophylactic LN irradiation in dogs with high grade mct

pfs

A

Treating the locoregional lymph nodes with radiation and/or surgery significantly improves outcome in dogs with high-grade mast cell tumors

Prophylactic LN radiation pfs >2381d (6yr) vs 197d (6.5 mo)

266
Q

Phosphorylated KIT as a predictor of outcome in canine mast cell tumors treated with toceranib phosphate or vinblastine

A

Pkit was associated with aberrant kit localization, high mc, and high grade

Pkit was the only independent predictive factor for ost in multivariate

MC was the only independent predictive factor for PFI

267
Q

does adjuvant medical therapy provide benefit to dogs with low grade mct

A

no

268
Q

mst high grade mct

A

1046 d (34 mo)
80% 1 year survival
73% 2 year survival

269
Q

local recurrence of high grade mct

A

18.4%

270
Q

regional LN mets of high grade mct

A

12%

271
Q

development of new mct of high grade mct

A

30%

272
Q

negative prognostic factors for high grade mct

A

high mc and tumor diameter

Tumor location, margins, and use of chemo did not affect MST

273
Q

is nanog associated with proliferation

A

not in mct

274
Q

Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib effect on mast cells

A

suppress IgE-dependent histamine release in primary MCT and may exert anti-proliferative effects

275
Q

Factors affecting prognosis in canine subcutaneous mast cell tumors

A

LN mets - mst 552d (17 mo) v 1722 d (4.5 yr)
local recurrence - mst 551d (17 mo) vs 1722d (4.5 yr)
infiltrative - 268d (9 mo) vs not reached

276
Q

Grade II Subcutaneous Mast Cell Tumors Treated with Surgery Alone
outcome
neg prog factor

A

PFS 1474d(4 yr), DFI not reached, OST not reached

AgNOR neg prog factor

277
Q

use of ultrasound as a predictor of liver or spleen mct mets

A

US poor predictor of metastasis with sens 67%, spec 68%, PPV 21%, NPV 94% in the spleen
Worse in the liver 29% sens, 93% spec, PPV 56%, NPV 82%

278
Q

effect of spleen and liver mets on top and mst

A

TTP for no mets not reached, early mets 305d, mets 69d
MST for no mets not reached, early mets 322d, and mets 81 d

279
Q

stage 4 mc tumors prognostic factors

A

tumor diameter >3 cm, more than 2 metastatic sites, bone marrow infiltration, and lack of tumor control at the primary site were confirmed to be negative prognostic factors by multivariate analysis

local tumor control predict a better outcome

anatomic location of the primary tumor, histo-pathological grade, mutational status, type of treatment and onset of treatment-related toxicity were not significantly associated with either PFI or ST

280
Q

mst of stage iv mct

A

110d (3-4 mo)

281
Q

how does BAX expression affect outcome of mct

A

BAX expression was associated with higher mortality rate and shorter survival.

BCL2 expression was significantly lower in high grade MCTs

deregulation of the intrinsic apoptotic pathway is present in cutaneous mct

282
Q

mastocytosis vs multiple distant mets - which is worse fo mct

A

mastocytosis worse prognosis

one met is better than multiple

283
Q

dogs with mastocytosis does anything affect survival

A

chemo increased survival
CVP better than palladia
ost 119d (~4mo)

284
Q

does pre surgical mct biopsy grading predict post surgical grading

A

yes
96% concordance with patniak
92% concordance with kiupel

Wedge 92% accurate, punch and needle core 100%

Discordant results underestimated the grade of the tumor but are sufficient

285
Q

mct on the pinna was is th most likely SNL

A

superficial cervical in 94.4% of cases

286
Q

prognosis of mct on the pinna

A

Median TTP 270 days (9mo) and TSS 370 days (12 mo)
only high grade was associated with decreased survival

287
Q

lysyl oxidase (LOX) enzyme expression in cMCT associated with grade

A

Cytoplasmic +LOX sig. Higher in high grade tumors

288
Q

when is marginal mct excision acceptable for tumor control

A

Marginal excision of low- to intermediate-grade MCTs is an acceptable approach if followed by treatment with RT - no gross disease

two-year control rates of 85% to 95%

289
Q

what species exhibits mast cell erythrophagocytosis

A

cats

290
Q

what breed of cat is more likely to develop cmct

A

siamese

291
Q

behavior of compact mastocytic feline mct

A

less commonly metastasize

292
Q

anaplastic mastocytic feline mct behavior and histo

A

anaplastic tumors may have a high MI, marked cellular and nuclear pleomorphism, and infiltration into the subcutaneous tissues.

reported to behave in a more malignant manner with metastasis to LNs and the abdomen - new study shows most are benign

293
Q

most common site of cmct in cats

A

head and neck esp pinna

294
Q

common misdiagnosis for histocytic feline mct

A

granulomatous nodular panniculitis or deep dermatitis

mast cells may comprise on 20% of the cells with lymphoid aggregates and eos

may not have granules

295
Q

ihc feline mct

A

vimentin, α-1 antitrypsin, and KIT

296
Q

prognostic factors for cMCT in cats

A

high MI appear to be at greatest risk for local recurrence and metastasis,

proposed MC 5

297
Q

RR of strontium 90

A

98% control rate - mst >3 yr

298
Q

RR feline cMCT to ccnu

A

50% ORR

50-60mg/m2
response duration 25 to 727 days (24 mo)

299
Q

most common intestinal mct location

A

SI > colonic

300
Q

prognostic factors for intestinal mct

A

histologic differentiation, MC >2

c-kit was not prognostic

301
Q

what is the rate of metastasis of osa to the local lymph node

A

<10% - 4.4% at the time of amputation

302
Q

what site of osa is least likely to fracture

A

distal radius

303
Q

what is the mst of a dog with axial osa who has mandibulectomy

A

> 2 year

304
Q

how does the addition of pamidronate to RT affect canine osa outcome

A

unlikely to change survival but improves chance of pain control

305
Q

prognostic factors for survival for osa

A

Increased weight
humerus location
stage - ln mets
grade,
monocytosis,
leukocytosis,
ALP,
low CD8/Treg
mod to high p53 staining
Telangiectatic (for ulnar OSA)
# of nodules on CT - but not whether or not there are nodules
strong cox2 staining

306
Q

prognostic factors for DFI for osa

A

humerus location
stage (LN mets)
monocytosis,
leukocytosis,
ALP
veg<50% shorter dfi

307
Q

criteria for limb sparing sx for osa

A

<50% bone involved, no fx, one limb, <360 degree ST involved,
radius/ulna best;
no local chemo treatment or RT

Contraindications 🡪 >50% bone involvement, location

308
Q

outcome and complications of limb spare surgery for osa

A

High infection 40-50%,
recurrence 20-60% with incomplete and more likely to met;
Do as good as amp+chemo; 80% good limb function

309
Q

osa t regs

A

low CD8: t reg ratio sig shorter ST than high ratio

310
Q

what is the most likely tumor to cause HO

A

OSA, TCC

311
Q

greyhound with lytic lesion in the ulna on bx it looks like tOSA. what is the next step?

A

request IHC FVIII/vWF.
amputation etc

312
Q

what is the effect of palladia on OSA

A

not benefit as a single agent

313
Q

What are risk factors for OSA?

A

Neutered rottweilers,
RT,
unrepaired fx,
metal implants,
chronic osteomyelitis,
age,
weight bearing bones,
hereditary

314
Q

Do pulm nodule seen on ct change prognosis for osa if not seen on cxr

A

no change in ST

315
Q

what distinguishes tOSA from HSA

A

FVIII/vWF

cells lining blood-filled spaces demonstrated positive FVIII-RAg/vWF immunoreactivity were HSA

316
Q

what percent of appendicular HSA are miscatergorized as tOSA without the use of IHC

A

20%

317
Q

what cancer has mutations in STAT3 and p53

A

OSA

318
Q

What effect does ZOL have on expression of chemokine receptors in OSA?

A

zol reduced CXCR4 expression by 40% within the primary tumor

319
Q

What is true of radiosensitivity and repair of sublethal RT-induced damage in OSA?

A

ɑ/β low = higher dose/less fractionation indicated

Upregulated p53 in OSA increased radiosensitivity

Surviving cell fractions at 2 Gy: 0.6

320
Q

what tumors express PD-L1

A

o Melanoma
o OSA
o Mammary
o Prostatic adenocarcinoma
o TCC
o HSA

321
Q

What is the relationship between Wnt and β-catenin in K9 OSA?

A

Moderate-high expression of β-catenin associated with development of mets
- No relationship with with DFI and OST
- No mutation in exon 3

322
Q

Why are carboplatin and gemcitabine synergistic/what results when given together?

A

both cause dec dna synthesis (induces cell cycle arrest and apoptosis). gemcitabine decreases DNA repair via dec ribonucleotide reductase - NER which is how carbo adducts are repaired

323
Q

What cytokines have been used in vet med therapy?

A

IFNy-mostly FeLV cats FISS-tolerated
IL2 inhaled in OSA mets was tolerated

324
Q

Which is more aggressive OSA mandible or maxilla?

A

Maxilla MST 5-10months recurrence 83-100%

mandible 15-18months

325
Q

mst for mandibular osa with surgery
does chemo work?

A

MST 525d (17.5 mo)
mst chemo 1023d (35 mo) - not stat sig but on multivariate analysis not having chemo was significant as was histologic grade

326
Q

met rate of mandibular osa

A

58% developed mets

327
Q

What is the survival of skull OSA?

A

Complete resection >1503days - 50 mths vs.
128d - 4 mths with incomplete

328
Q

What is survival with sx for multi lobular osteochondrosarcoma?

A

800-1332 ( 2- 4 yrs) complete resection vs. 330 days incomplete

329
Q

What is recurrence by grade of mlo?

A

Grade3 78% MST 11 months,
Grd2 47-60% MST 22 months,
Grd1 30% MST 50 months

330
Q

what is the time to metastasis in MLO

A

426-522 days
so can do pulmonary metatestecomy

331
Q

Which site in dogs is affected more with OSA? Cats?

A

dogs - Appendincular, forelimbs 2x as hindlimbs;

Cats appendicular 2x as axial, hindlimbs are most common

332
Q

Describe location and survival time for dog OSA?
- I think these are all sx and chemo

A

Distal carpus/tarsus MST 466days; 15mth
Rib 8months
Scapula 246days; 8 mth
Mandible 70% 1yr survival;
Maxilla 5months;
spine 4months,
extraskeletal 5months;
Skull 204days 7 mth

333
Q

ST of rib osa
sx alone
sx and chemo

A

sx alone - 3 mo
sx and chemo - 8 mo

334
Q

What is the risk of mets and associated survival for OSA?

A

15% @ dx lung mets-MST 59days;
4.4% Ln-MST 59days;
7.8% bone mets-MST 132days - 4 mths

335
Q

What are genetic and molecular mutations that affect OSA?

A

P53, Rb, HGF/MET, IGF, GH, PTEN, MMP2&9, ckit, PDGF, RANKL, ezrin, COX2, VEGF, STAT3, Wnt, integrin, survivin, RON

336
Q

What is the survival for amputation alone for OSA?

A

135-168days
4.5 -5.5 mths

337
Q

What is the survival for cats with OSA?

A

Amputation MST 22-44 months,
No chemo needed

338
Q

What is the survival with RT+chemo for OSA?

A

209 days - 7 mths
Skull MST 265days - 9 mths

339
Q

What is the response for palliative RT in OSA?

A

74-93% respond,
takes 11-21days,
last for 56-130days ( up to 4 mths)

340
Q

What is the general response/survival with amp+chemo for osa?

A

MST 9-12months with variety of tx-cisplatin, carbo, dox, alternating carbo/dox or cis/dox

341
Q

What other chemo drugs have been used as inhalants or oral?

A

Satraplatin-659days (6dogs) oral,
Dox & paclitaxel inhalant-fibrosis;
Gemcitabine-not good;
Palladia lung mets 1PR 43.5% stable

342
Q

What impact do bisphosphantes have on OSA?

A

Palliative 28% responded >4months, RT+dox+pam-bloodwork better but owner did not notice;
Another RT+chemo+pam-the RT+pam group did the worst 69days

343
Q

What type of OSA is less aggressive?

A

Parosteal or juxtacorticol

344
Q

What is the most common site for chondrosarcoma in the dog? and MST

A

Nasal cavity
MST 210-580 days (7-19 mo) various tx

345
Q

What is different between dog and cat Multiple cartilagenous exostosis MCE?

A

Cat - skeletally mature, rare on long bones, virally induced, aggressive behavior poor prog

Occurs AFTER skeletal maturity in cats (v. dogs which resolve at the time of skeletal maturity)
FeLV positive

346
Q

What tumors have kit mutations?

A

MCT, FISS, OSA, interstitial/Leydig, RCC, thyroid, melanoma, AGASACA, AML, HS & HSA(?)

347
Q

ALP and osa

A

No significant difference in cell proliferation, migration, invasion, or chemo Sn btwn cell lines assoc w normal and increased ALP serum conc

in vitro study

348
Q

rate of pathologic fracture of osa
common location

A

38% - 40%
femur most commonly affected (57.1%), followed by tibia (52.9% one study showed tibia more), humerus (37%), radius (20%), ulna.

349
Q

what type of surgery for rib osa

A

en bloc - 1 rib cr and cd

350
Q

samarium given to dogs with osa
- benefit?

A

32 dogs w appendicular – 63% had improvement in lameness within 2 weeks of 1st dose, 25% had no change, and 12% had worsening
o Overall MST 100 d
o No sig difference in MST of 134 d for historical cohort that underwent amp alone

351
Q

Samarium for MLO
benefit?

A

No clinically important AEs w Sm-EDTMP documented

▪ 20% had subjective improvement
▪ MST 144 d

352
Q

Periosteal osa

A

arising from inner periosteum, appears radiographically aggressive and is also biologically intermediate like intramedullary OSA

pfi 461 d ost 555d

353
Q

Parosteal OSA

A

arises from outter periosteum, appears radiographically LESS aggressive and is also biologically LESS aggressive

pfi 350 d - ost not reached

354
Q

Prognostic factors of appendicular chondrosarcoma w surgery

A

tumor grade - survival

355
Q

mst for rib chondrosarcomas based on grade

A

Grade 1 - >2723 d, 7yr
Grade 2 - 853 d, ~2yr
Grade 3 - >3820 d

found the paper this is correct
MST for dogs with rib chondrosarcoma was not reached (mean 1301 days) and survival was significantly greater than all other types of rib tumors

356
Q

duration and RR with “boom boom” RT 2 x 10 gy

A

93% subjective improvement in pain within 14 days
duration of response 80 days (2.5 mo)

357
Q

MST and met rate for appendicular chondrosarcoma in dogs for each tumor grade

A

o Grade 1 – 0% pulmonary mets, MST 6 yr
o Grade 2 – 31% mets, MST 2.7 yr
o Grade 3 – 50% met, MST 9 mo

358
Q

rate of path fracture following RT to osa

A

36% - same as no rt
developed fx 24-250 d following rt

359
Q

AE seen with RT to OSA

A

gr 1 skin tox most common SE

360
Q

Carboplatin v. carbo/doxo for OSA

A

Dogs receiving carbo alone had sig longer DFI (425 d 14 mths v. 135 d 4.5 mth) than dogs receiving alternating carbo/doxo

Tox similar btwn groups

361
Q

criteria for osa metastectomy

A

Primary tumor in CR – preferably for long relapse-free interval (>300 d)
One or two nodules on plain CXR
Cancer only found in lung (neg bone scan)
Long doubling time (>30 d) w no new visible lesions w/in this time

362
Q

ost and mst after metastectomy isa

A

ost 487 d (16 mo)
MST after metastectomy was 176 d - 232 d (6-7mth) following development of stage III dz, sig improved from no metastectomy (49 d after stage III dz)

363
Q

mst of ulnar telangiectatic osa

A

MST 208 d (7 mo) (compared to 463 d (15 mo) for other histo subtypes in ulna)

364
Q

expression of ​​PD-L1, HVEM, and B7H3 in osa cell lines versus mets

A

higher expression in mets
poss biomarker

365
Q

Evaluation of microwave ablation for local treatment of dogs with distal radial osteosarcoma

A

pilot study
tumor necrosis varied btw 30 - 90%
no immediate complications

366
Q

Percutaneous microwave ablation of solitary presumptive pulmonary metastases in two dogs with appendicular osteosarcoma

A

one pneumothorax
it is possible

367
Q

Lateral manus translation for limb-sparing surgery in 18 dogs with distal radial osteosarcoma in dogs
dfi
mst
complication

A

Complications - infection, biomechanical, local recurrence
DFI 219d (7mo)
MST 370d (1 yr)

368
Q

Effect of surgical site infection on survival after limb amputation in the curative-intent treatment of canine appendicular osteosarcoma

A

DFI 236 days - 7 m
OST 283 days - 9 m

DFI and MST did not differ between groups - SSI vs not

369
Q

most common location of appendicular hsa

A

tibia
78% of hsa tumors were in the hind limb

370
Q

ost with chemo and amp for appendicular hsa

A

9 months - more aggressive treatment = better outcome

371
Q

ost with chemo and amp for tOSA

A

7 months

372
Q

Outcome and Metastatic Behavior of Canine Sinonasal Osteosarcoma

A

30% metastatic rate with median time to metastasis 458 days, mets more common to LN then lungs

Medium time to local progression was 335 days

OST 410 days

373
Q

Prognostic value of fluorine18 flourodeoxyglucose positron emission tomography/computed tomography in dogs with appendicular osteosarcoma

A

Maximum standard uptake value SUV of the primary tumor was significantly negatively associated with the OS

Ost SUV >7.4 = 254 d - 8 mth
Ost SUV < 7.4 = 680 d - 23 mth

374
Q

Role of Periostin Expression in Canine Osteosarcoma Biology

A

Periostin mRNA and protein expression upregulated >40 fold in canine OSA compared to normal bone

Not associated with time to metastasis

Associated with pro-tumorigenic pathways including WNT, EM transitions, and angiogenesis

375
Q

Autologous cancer cell vaccination, adoptive T-cell transfer, and interleukin-2 administration in dogs with osteosarcoma
- toxicity
- dfi
- mst

A

low grade toxicity with premeds
DFI 213 d (7.7mo)
MST 415 d (13 mo) 5 dogs lived >730d (2 yr)

376
Q

where is an abnormal met location that can be the first location deteted in osa?

A

skin/SQ

377
Q

dog with appendicular osa - skin nodules noted to be mets - what is the pulmonary metastatic rate ?

A

85% to lungs
5% to the bone

378
Q

dog with appendicular osa - skin nodules noted to be mets. what is the prognosis after identification of mets

A

grave <2 mths

Survival with surgery and chemo 94 d or chemo alone 64d no treatment 11d

379
Q

Adverse events and outcomes in dogs with appendicular osteosarcoma treated with limb amputation and a single subcutaneous infusion of carboplatin

A

7% hospitalization rate for GI AE from chemo
NOT RECOMMENDED d/t low survival
MST 196d - 6/5 mth

380
Q

Evaluation of metronomic cyclophosphamide chemotherapy as maintenance treatment for dogs with appendicular osteosarcoma following limb amputation and carboplatin chemotherapy

A

No benefit
58% developed cystitis

381
Q

does Auranofin improve overall survival when combined with standard of care in a pilot study involving dogs with osteosarcoma

A

yes - translational study

survival times ranging between 806 and 1525 days in males

382
Q

Timing of adjuvant chemotherapy after limb amputation and effect on outcome in dogs with appendicular osteosarcoma without distant metastases

A

TTP longer for dogs who received chemo </= 5 days of amp 375 d vs >5d 202d

OST longer too 445d 14.8 mth vs >5d 239d 8 mths survival

383
Q

what RT protocol + chemo for osa has better survival times

A

ST longer in dogs receiving SRT+chemo 350d - 11 mth vs fxRT + chemo 147d - 5 mth

any RT was better than none as long as baseline pain scores were low and RT dose high

384
Q

what were prognostic factors for survival with isa when Rt was given with chemo

A

low baseline pain score
high rt dose

pain and rt dose did not impact survival in dogs who did not receive chemo

385
Q

Safety evaluation of the canine osteosarcoma vaccine, live Listeria vector

A

AE generally mild and self limiting: nausea, lethargy, fever

8% developed Listeria + abscesses (3 at amp site, 1 septic stifle, 1 bacterial cystitis, 1 lung masses)

386
Q

what is the osa vaccine

A

vax targeting the dominant immune epitopes of HER2 was developed using a highly attenuated recombinant Listeria monocytogenes

resulted in improved OST in 18 dogs receiving amp, platinum chemo (956d (31 mo) vs historic control receiving standard of care tx 423d (14 mo))

387
Q

Outcome and prognosis for canine appendicular osteosarcoma treated with stereotactic body radiation 2021 study

A

84% max lameness improvement at 3 weeks for a median of 6 mo duration

41% fracture rate with 21% have amp after treatment; dogs with salvage amp had sig longer OST 346 - 11.5 mths vs 202 days - 7 mth

No difference in survival with 15 dogs who had mets

MST 233 days - 8 mth

388
Q

primary osteosarcoma of the digits, metacarpal and metatarsal bones
pfi
ost

A

pfi 377d - 12.5mth
st 687 - 23 mths

Chemo, lymphocyte and monocyte count no sig. effect

389
Q

how does perioperative pain control affect outcome in dogs with osa

A

Dogs treated with high intensity perioperative pain (NSAID, bupivcane locally) had a higher probability of survival than those not treated 378 d 12.5 vs 252d - 8 mths

390
Q

how does macrophage and lymphocyte infiltration affect outcome in canine osa

A

increased macrophages may be protective
lymphocyte infiltration did not correlate with outcome

391
Q

how to circulating tumor cells affect survival and metastasis in osa

A

dogs that had mets had a spike in CTCs 1 month before and had a shorter mst 10x more likely to die

392
Q

Feasibility and safety of whole lung irradiation in the treatment of canine appendicular osteosarcoma

A

Well tolerated only mild hematopoietic toxicity, pneumonitis, pulmonary fibrosis

393
Q

success of whole lung irradiation in the treatment of canine appendicular osteosarcoma

A

no change in dfi

394
Q

osa limb salvage surgery and secondary amp

how many needed it
reason
st after amp

A

84% of dogs with limb spare did not need to undergo secondary amputation

Reasons - local recurrence and surgical site infection

Dogs live 205 days beyond 2nd amp

amputation and ssi improved survival

395
Q

can you remove ilium only if it has osa

A

Iliectomy can be considered for a mass confined to the ilium when preservation of the limb is desired.

recurrence occured but not mets

396
Q

outcome of srt for mlo
10 gy x 3 f

A

well tolerated but remission was shortlived

397
Q

st of dogs with vertebral osa after palliative sx alone or combine wiht chemo and rt

A

sx alone - 42 days
sx and chemo - 82 days
only one dog treated wiht sx and rt - 101 d
6 dogs treated with all 3 - mst 261 d

398
Q

Nanoparticle hyperthermia and monocytes

A

Nanoparticle hyperthermia may increase in vitro monocyte chemotaxis

may aid with anti-tumore immunity

399
Q

Effects of the potassium-sparing diuretic amiloride on chemotherapy response in canine osteosarcoma cells

A

Amiloride strongly synergized with doxorubicin in combination treatment and exhibited additive or antagonistic effects with carboplatin in canine OSA cells.

Combination treatment with doxorubicin significantly upregulated p53-mitochondrial signaling to activate apoptosis and downregulate Akt phosphorylation

400
Q

does propranolol or carvedilol affect osa cell viability

A

Prolonged exposure to propranolol and carvedilol significantly decreased the surviving fraction of canine osteosarcoma cells after 3Gy radiation

401
Q

how do platinum drugs enter the cell

A

via CTR1

402
Q

what is one mechanism of platinum resistance

A

Atox1 aggregates platinum agents preventing then from forming DNA adducts

ATOX1 antioxidant 1 copper chaperone

403
Q

copper chaperones and osa response to carbo

A

Inhibition of copper chaperones (DC-AC50 smi of Atox1 and CCS) sensitizes human and canine osteosarcoma cells to carboplatin chemotherapy

404
Q

selective inhibitor of nuclear export (SINE) verdinexor (laserdia) exhibits biologic activity against canine osteosarcoma cell lines

  • how
A

SINE prevents tumor suppressor proteins from leaving the nucleus thereby allowing to carry out normal functions and kill cancer cells
Canine OS cell lines and primary OS subset cells have increase XPO1 compared to osteoblasts

All cells lines had dose dep. Growth inhibition with verdinexor

Verdinexor + doxo synergistic potent cell inhibition im 3 lines

405
Q

hedgehog pathway and osa cell lines

A

hedgehog/smoothened is activated in canine OSA cell lines and cyclopamine suppresses OSA survival via inhibition of SMO → possible signaling pathway may be druggable target

406
Q

S. aureus. infection affects osa
- how

A

downregulates TGF-β and heightens the inflammatory signature in human and canine macrophages to counteract osteosarcoma-induced immune suppression

Onco boards 2024 (17 decks)

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