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Oncology Boards > Hemangiosarcoma > Flashcards

Hemangiosarcoma Flashcards

1
Q

Recent molecular data suggests that HSA arises from ___ rather than from malignant transformation of mature peripheral endothelial cells

A

bone marrow progenitor cells that undergo dysregulated maturation

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2
Q

Mutations in ____ and ____ have been shown in the pathogenesis of angiosarcoma in mic and humans but are infrequent in canine HSA

A

p53 and Ras

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3
Q

What key growth and apoptosis regulating proteins are overexpressed in HSA compared to hemangiomas or normal tissues

A

pRB, cyclin D1, Bcl2 and survivin

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4
Q

Two large studies have shown _____ of dogs with splenic tumors have malignant disease and ______ of these are HSA

A

50%; 50-74%

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5
Q

What IHC can be used to support diagnosis of HSA and rule out other sarcomas

A

CD31/platelet endothelial cell-adhesion molecule von Willebrand’s factor (factor VIII-related antigen)

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6
Q

What RBC changes are common in dogs and cats with HSA

A

schistocytes, acanthocytes and nRBCs

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7
Q

Thrombocytopenia is found in _____% of HSA

A

75-97%

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8
Q

Alterations in secondary coag parameters (PT and PTT, fibrin degradation product, fibrinogen and d-dimers) are found in nearly _____% of patients with HSA

A

50%

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9
Q

More than 50% of cats with HSA may have elevations in this chemistry value

A

AST

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10
Q

What are the “T” classifications for HSA

A

0 = no evidence of tumor T1 = tumor <5cm diameter and confined to primary tissues T2 = tumor ≥5cm, or ruptured or invading into SQ tissues T3 = tumor invading adjacent structures including mm

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11
Q

What are the TNM stages for HSA

A

I = T0 or T1, N0, M0 II = T1 or T2, N0 or N1, M0 III = T2 or T3, N0, N1 or N2, M1

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12
Q

What is significantly elevated in dogs with cardiac HSA compared to HSA at other sites, dogs with other cancers, etc

A

cardiac troponin-1 also higher for HSA pericardial effusion vs. non-HSA pericardial effusion

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13
Q

What is the MST for dogs with cardiac HSA treated with hypofractionated RT?

A

MST 2.5mo + decreased frequency of cardiac tamponade

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14
Q

The original eBAT trial showed what?

A

MST 8.5mo, 6-mo survival of 70.6% (treatment before standard of care dox), six long term survivors All dogs were stage I or stage II

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15
Q

What is the MST for dogs with stage I splenic HSA treated with surgery + chemo?

A

MST 239-355d

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16
Q

What is the MST for dogs with stage II splenic HSA treated with surgery + chemo

A

MST 120-148d

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17
Q

MST for dogs that were treated with surgery + thalidomide for splenic HSA? What was the 1yr survival rate? (Bray JSAP 2018)

A

MST 172d

33% of dogs alive >1 yr post-op (range 458-660d)

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18
Q

For dogs with splenic HSA treated with thalidomide, what was prognostic for survival? (Bray JSAP 2018)

A

Stage II better than stage III (303d vs. 40d)

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19
Q

What was the affect of yunnan baiyao and aminocaproic acid in dogs with right atrial masses for number of pericardiocenteses performed and the rate of recurrence of signs? (Murphy JVECC 2016)

A

No difference in treated dogs (YB alone or YB +AA) compared to pericariocentesis only dogs for number needed, recurrence of signs or MST

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20
Q

What did yunnan biayo cause in HSA cell lines?

A

Dose and time dependent cell death through initiation of caspase-mediated apoptosis

No sig. changes in VEGF levels

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21
Q

How was the HSA tumor vaccine made and what was the dosing schedule? (U’Ren JVIM 2007)

A

Lysates of allogeneic HSA cell lines mixed with adjuvant of liposome-DNA complexes

8 vaccines over 22wks

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22
Q

What was the outcome in dogs treated with the HSA tumor vaccine? (U’Ren JVIM 2007)

A

Dogs mounted strong Ab responses

MST 182 days for stage II HSA treated with vaccine + doxo

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23
Q

Yunnan Baiyao increases apoptosis in HSA cell lines by what mechanism (Wirth VCO 2014)

A

by caspase 3/7 and TUNEL

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24
Q

What is L-MTP-PE and what cancer type was it investigated in? (Vail, Clin Can Research 1995)

A

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy - synthetic derivative of bacterial cell wall - increases monocyte tumoricidal activity and increases TNF alpha and IL6

HSA

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25
Q

What is e-bat? **Borgatti VCO 2020

A

EGF bispecific angiotoxin

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26
Q

What was the outcome for dogs treated with eBAT 1-wk post splenectomy and 1wk prior to dox 1, 2, 5th chemo? **Borgatti** VCO 2020

A

No survival benefit for eBAT treated dogs compared to contemporary comparison of dogs with stage 1-3 HSA treated with surgery + dox

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27
Q

What was the MST for dogs with stage 1 or 2 splenic HSA treated with anthracycline chemo and/or metronomic chemo after splenectomy? (Treggiari VCO 2019)

A

Antracycline: 154d

Anthrcycline followed by metronomic 338d

Metronomic alone 225d

Not statistically different

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28
Q

What was the MST for stage III HSA treated with maximal tolerated chemo vs. metronomic vs. splenectomy alone? (Marconato VCO 2019)

A

MTD ST 140d

MC 58d

sx alone 40d

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29
Q

What was the mst for dogs with HSA (any stage) with maximally tolerated chemo (doxorubicin or ctx) vs. MTD chemo followed by metronomic cytoxan (Alexander JSAP 2018)

A

No stat difference

MST for MTD chemo = 180d

MST for MTD chemo + metronomic = 212d

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30
Q

In the Finotello VCO 2016 study, dogs treated with doxo followed by metronomic chemo had a significantly longer MST (not reached) than dogs with doxo alone (168d). What was different about this metronomic protocol compared to other studies?

A

70% of dogs also on thalidomide for metronomic - Bray study suggests thalidomide after surgery have a better MST

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31
Q

Doxorubicin combined with what other chemotherapy improved MST for dogs with HSA compared to doxo/cytoxan (Finotello VCO 2015)

A

DTIC (dacarbazine) MST 550d

Dox/Cytoxan = 100-150d

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32
Q

What was the MST for dogs treated with surgery alone for splenic HSA? What was prognostic? (Wendelburg JAVMA 2015)

A

1.6mo

Stage prognostic

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33
Q

What was the MST for dogs treated with splenectomy + dox followed by continuous Palladia for stage I or II HSA? (Gardner BMC 2015)

A

MST 172d - no improvement compared to sx+dox alone

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34
Q

Was doxorubicin or doxil (liposome encaspulated dox) more effective for adjuvant therapy for splenic HSA in dogs? (Teske VCO 2011)

A

trick question - no difference b/w treatment groups

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35
Q

What were the unique AEs associated for doxil in dogs with HSA compared to those treated with doxo? (Teske VCO 2011)

A

desquamating dermatitis like palmar-plantar erythrodysesthesia (PPES) was seen in two dogs, while three other dogs showed anaphylactic reactions.

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36
Q

What was the MST for dogs treated with splenectomy + epirubicin for HSA? Why might this not be better than dox? (Kim JAVMA 2007)

A

MST 144d, but 7/18 dogs hospitalized for GI AEs (higher than rate for doxo)

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37
Q

What was the result in dogs treated with ifosfamide alternating with dox for HSA? (VCO 2003)

A

No imporvement in MST (149d.)

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38
Q

What is the DAV protocol for HSA? (Dervisis JAAHA 2011)

A

Doxo + DTIC day 1

Vinc d. 8 and 15

repeat

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39
Q

What was the ORR and MST for dogs with stage II and II HSA treated with DAV? (Dervisis JAAHA 2011)

A

RR 47.4% (CR in 5)

MST 125 days

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40
Q

What was associated for a better outcome in dogs with stage II or III HSA treated with DAV? (Dervisis JAAHA 2011)

A

Needing a dose reduction in dacarbazine

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41
Q

What is the VAC protocol for HSA? (Alvarez JAAHA 2013)

A

Day 1 doxorubicin

day 8 vinc

day 10 ctx

day 15 vinc

dogs on TMS at all times

42
Q

What was the ORR response and MST for dogs treated for HSA with VAC?

A

ORR 86% - no difference in survival between stage I/II (189d) vs. stage III (195d) - may be better for advanced stage HSA?

43
Q

What was the ORR and MST for dogs with presumed cardiac HSA treated with doxorubicin (Mullin VCO 2014)

A

ORR 41%

MST 116d

44
Q

What was the MST for dogs with cutaneous HSA (Nobrega J Comp Path 2019)

A

12mo - study didn’t mention differences for stages (ie. cutaneous vs. sq vs. mm)

45
Q

What IHC labeling was associated with OS in dogs with cutaneous HSA (Nobrega J Comp Path 2019)

A

trick question - none of the ones looked at had an impact on OS

(FVIII, COX2, VEGF, PCNA and Casp-3)

46
Q

What was the MST for dogs with dermal HSA treated with surgical excision (Szivek VCO 2011)

A

MST 987d

Dogs with predisposition (whippets, pitties, it greyhound, etc) better (1570d) than non-predisposed breeds (593D)

47
Q

What were positive prognostic factors for survival in dogs with dermal HSA? (Szivek VCO 2011)

A

Predispose breed, solar induced, ventral abdomen

48
Q

What was the ORR for dogs with nonresectable HSA treated with doxorubicin? What improved this? (Wiley VCO 2010)

A

ORR 38.8%

Dogs that had complete sx excision after neoadjuvant chemo did better (207d vs. 83d)

49
Q

What were prognostic factors for OST in dogs with SQ or IM HSA? (Shiu JAVMA 2011)

A

adequate local control

<4cm size

mets at dx

gross disease

50
Q

What other than cardiac neoplasia, what is a dx for nontraumatic hemothorax? (Rutherford JAAHA 2016)

A

Intrathoracic, extracardiac HSA

Surgery can be palliative - 1 dog alive 1mo post-op, 1 alive 5mo, 1 euthanized on table because not resectable

51
Q

What was the MST for dogs with right atrial masses + pericardial effusion treated with doxorubicin alone? (Ghaffari JSAP 2014)

A

MST 139.5d.

52
Q

What was the MST for dogs treated with nephrectomy +/- adjuvant chemo for renal HSA? (Locke JVIM 2006)

A

MST 278d, maybe better location for HSA

53
Q

What is the MST for lingual HSA? What was prognostic?

A

MST 533d - all low or intermed grade

positive prog = small size, absence of clinical signs

54
Q

What 4 predictors were used to calculate the risk score for HSA for dogs presenting with hemoabdomen? (Schick JVECC 2019) **Committee member**

A

weight

plasma protein

platelet counts

CXR findings

55
Q

What was the incidence in low, medium or high risk groups based on the HELP score for dogs presenting with hemoabdomen? (Schick JVECC 2019) **committee member**

A

Low: 36%

medium 76%

high 96%

56
Q

What PET CT better at staging/monitoring dogs with HSA? (Borgatti PLoS one )

A

9 dogs - also getting eBAT

pet CT found two lesions that weren’t found on routine imaging + they were larger with higher metabolic activity on second scan

57
Q

What characteristic on CT may be different for nonparenchymal HSA compared to other STS? (Fukuda VRU 2014)

A

Presence of intense foci of contrast enhancement (13/17 dogs with HSA) - not typical for other STS

58
Q

What is the rate of cardiac masses in dogs presenting with splenic HSA? (Boston JAAHA 2011)

A

8.7%

59
Q

What was the rate of a concurrent splenic HSA in dogs with cardiac HSA? (Boston JAAHA 2011)

A

29%

42% had mets to other site as well

60
Q

What marker was higher in dogs with HSA than normal dogs, but was not different in dogs with a hemoabdomen for HSA vs. benign causes of hemoabdomen? (Thamm VCO 2011)

A

Serum Thymidine Kinase 1

61
Q

What ultrasonographic feature of the spleen is suggestive of malignancy in cats? (Bertal JFMS 2017)

A

The presence of a splenic mass >1cm on AUS

62
Q

What appearance on AUS of the spleen was NOT correlated with the presence of malignancy in cats? (Bertal JFMS 2017)

A

Moth-eaten appearance

63
Q

What was the MST for cats with cutaneous HSA? (McAbee JAAHA 2005)

A

Majority SQ

MST >1460 days with surgery (only 60d w/o)

64
Q

What are the most common clinical signs for cats with visceral HSA? (Culp JVIM 2008)

A

Lethargy, anorexia, respiratory difficulty, collapse

65
Q

The majority of cats (82%) had what abnormality on CBC? (Culp JVIM 2008)

A

Anemia

66
Q

What was the rate of lung metastasis in cats with visceral HSA (Culp JVIM 2008)

A

33% lung mets

67
Q

What was the rate of multifocal disease (and where was it) in cats with visceral HSA? (Culp JVIM 2008)

A

Overall 77%

Liver 35%

SI 31%

LI 31%

Abd LN, mesentery, spleen 23%

brain 8%

68
Q

What was the MST for cats with visceral HSA (Culp JVIM 2008)

A

Most euthanized w/in 1 day of dx

For those that weren’t, MST 77d

69
Q

What has been associated with shorter survival times in cats with HSA (Visceral or cutaneous) (Johannes JAVMA 2007)

A

MI >3/10hpf

70
Q

What factors were associated with survival time (on univariate) analysis in dogs with stage II splenic HSA treated with sx + chemo? Also, what chemo was used? (Moore JAVMA 2017)

A

Chemo was combination of CCNU + either doxo (25), mito (4) or epirubicin (1) +/- metronomic CTX (5)

Factors on univariate: MI, Tumor differentiation, histo grade CCNU dose, metronomic chemo

71
Q

What factors were associated with survival time (on multivariate) analysis in dogs with stage II splenic HSA treated with sx + chemo? (Moore JAVMA 2017)

A

MI only signficant factor - score 0 or 1 better than ≥2

Score 0 = <11 MI (MST 292d, 1yr survival 42%

Score 1 = 11-20 MI, MST 212d

2 = 21-30, MST 118d

3 = >30, MST 116d

72
Q

What was the overall MST and 1yr survival rate for stage II HSA treated with splenectomy + CCNU based chemo in dogs? (Moore JAVMA 2017)

A

MST 158d, 1yr survival 16%

73
Q

What is the problem with CD31 IHC for differentiating HSA from other nonendothelial tumors? (Ramos-Vara, Vet Path 2018)

A

Has cross-reactivity with other tumor types (plasmacytoma, AGASACA, carcinoma) and normal tissues

74
Q

What were the IHC characteristic of canine angiosarcoma? (Bertazzolo Vet Clin Path 2005)

A

IHC majority positive for both CD31 and FVIII-related Ag

75
Q

What are the growth patterns of HSA and what is their influence on survival in dogs? (Goritz J Comp Path 2013)

A

Cavernous, capillary or solid

NOT PROGNOSTIC

76
Q

What was the incidence of metastatic HSA in dogs with grossly abnormal appearing livers at time of splenectomy? (Clendaniel JAAHA 2014)

A

50%

If grossly normal, no dogs had mets

77
Q

What gross liver apperance was highly associated with metastatic HSA in dogs undergoing splenectomy for HSA? (Clendaniel JAAHA 2014)

A

Multiple nodules, dark colored nodules, bleeding nodules

78
Q

What was the response to HSA cell lines treated with TRAIL? (Goto VCO 2019)

A

TRAIL = tumor necrosis factor-related apoptosis-inducing ligand

2 recombinant human TRAILS decreased cell viability

some increased caspase 3 and 8 leading to ADP ribose polymerase degredation and apoptosis

79
Q

What pathway dos resveratrol activate in canine HSA cell lines and what was the result? (Carlson VCO 2018)

A

Activated p38 MAPK pathway –> inhibited growth, induced apoptosis, augmented doxo effects

**did not impact AMPK or ERK1/2 pathways**

Resveratrol is a stilbenoid, a type of natural phenol, just btdubs.

80
Q

What cancer cells were found to express procoagulant tissue factor (TF) (Witter AJVR 2017)

A

Canine HSA cell lines

81
Q

What is tetrathiomolybdate (TM) and what does it do to canine HSA cells? (Sloan AJVR 2017)

A

TM = copper chelator

Dox + TM –> greater decrease in proliferation and survival rates than each drug alone; also increased ROS formation and apoptosis

82
Q

Suppressing what with small interfacing RNA promoted apoptosis in HSA cell lines suggesting it may paly an important cytoprotective role (Anwar J Comp Path 2016)

A

Peroxiredoxin 6 (PRDX6)

83
Q

Big endothelin-1 has 100% sensitivity and 95% specificity for ____ (Fukumoto Vet J 2015)

A

canine HSA

84
Q

Serum VEGF is significantly higher or lower in dogs with spelnic masses compared to those without. Also, what is the difference between serum VEGF b/w hematoma and HSA? (Frenz Res Vet Sci 2014)

A

VEGF higher in dogs with splenic masses, but NO difference between hematoma and HSA

85
Q

Concentration of _____ is 9.5x higher in dogs with metastatic HSA compared to heatlhy dogs. It is also elevated in dogs with OSA, LSA, carcinoma and inflammatory disease, but to a lower amount than HSA (Kirby JVIM 2011)

A

liopcalin region of collagen 27alpha1 in serum

86
Q

What PTEN mutations have been detected in canine HSA? (Dickerson Vet Path 2005)

A

point mutations or deletions in c-terminal domain of PTEN

87
Q

What were the affects of masitinib on canine HSA cell lines? (Lyles VCO 2012)

A

Dose and time dependent decrease in cell proliferation

Induced apoptosis by activating caspase 3/7

88
Q

What markers can differentiate HSA and lymphangiosarcoma? (Halsey VCO 2014)

A

LYVE-1 and PROX-1 (specific for lymphatic endothelial cells)

89
Q

What chromosomal abberations have been identified in HSA? (Thomas and Modiano Csome res 2014)

A

CDKN2A, VEGFA and SKI

90
Q

In small-breed dogs with nodular splenic lesions, what was the incidence of HSA? Fernandez JAAHA 2019

A

27%

91
Q

In small breed dogs with splenic nodules, presence of what was associated with malignancy? Fernandez JAAHA 2019

A

Hemoabdomen - present in 31% of dogs, 66% of which had malignant lesions

92
Q

Of small breed dogs with splenic nodules, what breeds were most common and positively assoc with malignancy? Fernandez JAAHA 2019

A

Mini schanuzers, dachshunds beagles most common, beagles assoc’ with malignancy

93
Q

What factors were associated with a higher likelihood of HSA in dogs regardless of their size? (Sherwood, JAAHA 2016) **committee member**

A

pre-op anemia, hemoabdomen, thrombocytopenia, blood transfusions

94
Q

What was the difference in odds of having a malignant splenic lesion or HSA in small dogs vs. large dogs undergoing splenectomy? (Sherwood JAAHA 2016) **committee**

A

No difference in overall odds of malignancy but large dogs significantly more likely to have HSA compared to small dogs

95
Q

What was the rate of HSA vs hematoma for nontraumatic hemoab in dogs? (Aronsohn JAAHA 2009)

A

63.3% HSA, 26.6% hematoma (others = splenic torsion, HCC and carcinomatosis)

96
Q

Small dogs with spontaneous hemoabdomen are more likely to have bleeding from _____ compared to large dogs (Fleming Vet Surg 2018)

A

Liver and other sites - retroperitoneal mass, kidney, adrenal (vs majority spleen in large dogs)

97
Q

HSA associated with splenic bleeding occurs more commonly in small/large dogs (Fleming Vet Surg)? What are the other size more likely to have hemoab from?

A

Large

HCC, LSA, adrenal tumors, OSA, renal carcinoma - ie. not spleen

98
Q

What was the difference in DFI for dogs with HSA treated with surgery that received a blood transfusion vs. those that did not? (Ciepluch Vet Surg 2018)

A

Dogs w/blood transfusion 76d (1-836) vs. w/o 120d (38-916) but confounding factors present

99
Q

What risk factors were identified for dogs undergoing splenectomy? (Wendelburg JAVMA 2014)

A

Each decrease of 10,000 plt = odss of death increase by 6%

PCV < 30% odds of death 2x higher than if >30

Intraoperative arrhythmias increase risk of death 2x

100
Q

What was the response to HSA cell lines treated with TRAIL? (Goto VCO 2019)

A

TRAIL = tumor necrosis factor-related apoptosis-inducing ligand

2 recombinant human TRAILS decreased cell viability

some increased caspase 3 and 8 leading to ADP ribose polymerase degredation and apoptosis

101
Q

What gross liver apperance was highly associated with metastatic HSA in dogs undergoing splenectomy for HSA? (Clendaniel JAAHA 2014)

A

Multiple nodules, dark colored nodules, bleeding nodules

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