FISS Flashcards

1
Q

What two changes in the mid-1980’s in vaccines correlate with FISS development in cats?

A

Development of a killed rabies and killed FeLV vaccine - both have strong association with FISS development

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2
Q

What is the estimated prevalence of sarcoma development at sites of vx admin

A

1-4/10,000 up to 13-16/10,000 cases

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3
Q

What is the time from vaccine to tumor development for FISS?

A

Anywhere from 4wks up to 10yrs

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4
Q

Are adjuvanted vs. nonadjuvanted vx more likely to cause fiss?

A

No one knows - though it adjuvanted increases inflammation and therefore increases risk of FISS, but 3 large studies showed no evidence that aluminum-containing vx had more risk

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5
Q

What IHC markers are FISS positive for that non-FISS FSA’s are not (or are only weakly positive for)

A

PDGF, epidermal growth factor, TGF-beta

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6
Q

Lymphocytes in FISS are positive for ____ while lymphocytes in non-injection-site FSA and normal LN are negative this

A

PDGF (macrophages, too)

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7
Q

What proto-oncogene was strongly positive in ISS and not expressed in non-FISS FSA? What does it code for?

A

c-jun, codes for AP-1

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8
Q

FeLV and feline sarcoma virus are/are not involved in FISS pathogenesis?

A

Are not

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9
Q

Non FISS FSA typically arise from the ____ compared to FISS which typically arise from the ____

A

non-FISS FSA: skin FISS: SQ

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10
Q

What subtypes of tumors are included in FISS

A

FSA, rhabdoymyosarcoma, MFHs (malignant fibrous histiocytomas), undifferentiated sarcomas, extraskeletal OSA and chondrosarcomas

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11
Q

What do macrophages in the peripheral inflammatory cell infiltrates of FISS often look like/contain

A

bluish-gray foreign material - aluminum and oxygen

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12
Q

How should CT imaging be performed for intrascapular FISS

A

postcontrast CT with thoracic limbs extended cranially and caudally along body to better determine the association with the FISS and the adjacent tissue

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13
Q

What is the preferred surgical approach to FISS

A

5-cm lateral margins and two fascial layers deep for gross palpation 3cm lateral and one fascial layer deep for cats with CT to characterize extent of disease

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14
Q

What is the rate of complete excision for FISS when a 3cm/1 layer deep approach is used based on palpation vs. 5cm/2 layers?

A

3cm/1 layer = 50% complete 5cm/2 layer = 95-97%

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15
Q

What is the median DFI for marginal resection, wide resection and radical surgery for FISS

A

marginal 79d wide 325d radical 419d

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16
Q

What is the time to first recurrence for FISS when first surgery was at a nonreferral vs. referral practice

A

nonreferral 66d referral 274d

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17
Q

T/F wide surgical resection of FISS in the interscapular area usually requires removal of the dorsal spinous processes

A

T

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18
Q

Has preoperative RT been shown to reduce rate of recurrence in FISS treated with surgery?

A

Not in the literature - local recurrence with complete margins = 42% compared to incomplete for 32% of cats treated with pre-op RT + surgery

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19
Q

When should post-op RT start for FISS?

A

10-14 days post-op; DFI and ST decreases as the interval between surgery and RT increases

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20
Q

What is the rate of recurrence for FISS with multimodal treatment with surgery (2-3cm margins) + RT

A

28-45%

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21
Q

What was the response rate to hypofx rt (5x4gy) + liposomal DOX as a radiation sensitizer for cats with gross disease FISS?

A

90% ORR - 7 PR, 2 CR; problem = not durable (117d)

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22
Q

What was the median PFI and MST for cats treated for gross disease FISS with 4x8Gy RT?

A

PFI 4mo, MST 7mo

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23
Q

What is the response to SRT for gross disease FISS

A

Variable protocols (most 3x10Gy), 8/11 response (3CR, 5PR), median PFI 242d, MST 301d

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24
Q

What is the rate of metastasis for FISS?

A

0-26%

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25
T/F cats treated with gross residual disease after surgery for FISS with post-op RT and chemo had an improved MST compared to those only treated with surgery + RT
True - MST 29mo vs. 5mo (all chemo = doxo except 1 cat had doxo + cytoxan)
26
\_\_\_\_ Has been shown to result in inhibition of the PDGF/PDGFR pathway and results in chemosensitiaztion in FISS cell lines
Imatinib
27
\_\_\_\_\_ has been shown to inhibit PDGFR in FISS cell lines (but in concentrations higher than readily achieveable) and was/was not found to be a radiation sensitizer
Masitinib, was not a radiation sensitizer
28
What was the median time to local recurrence for FISS treated with surgery vs. intraop vs. post-op ECT with bleo?
Surgery only 4mo intraop bleo ECT = 12mo post-op bleo ECT = 19mo
29
T/F it is safe to treat cats with FISS with cisplatin ECT?
True - minimal systemic toxicity (pulmonary, renal, cutaneous); local recurrence 29%
30
What were the rates of recurrence for cats with FISS treated with surgery + iridium-based brachytherapy and IL-2
Human IL-2 w/ vaccina virus vector: 39% at 1yr Feline IL2 w/ canary pox vector: 28%
31
Intratumoral feline IL-2 has been combined with what other therapies in a phase I trial?
IFN-gamma and granulocyte-macrophage colony-stimulating factor + preop magnetofection
32
What is the 3-yr disease free rate for FISS when removed with 5cm lat margins or compartmental resections
86%
33
What are prognostic factors for local recurrence for FISS
Tumor size, surgical dose, completeness of histologic excision, histologic grade
34
What are the metastatic rates for grade I, II and III FISS
I: 0-17% II 15-19% III: 22-100%
35
What is the overall MST for radical surgery with 4-5cm/2layer deep for FISS?
804-901d
36
What are prognostic factors for survival in cats with ISS
PCV\<265%, tumor size (\<2cm vs. 2-5 vs \>5cm; or \<3.75cm in another study), treatment type, histologic subtype, mitotic rate (20) local tumor recurrence and mets
37
Where does the VAFSTF recommend feline vaccines be administered?
Rabies RHL FeLV LHL Other vaccines: right shoulder none interscapular
38
Is SQ or IM vaccine recommended by VAFSTF?
SQ because masses are easier to detect earlier
39
When should a mass at vaccination sites be investiaged further?
Mass is evident 3 or more months after vx If the mass is larger than 2 cm If the mass is increasing in size more than 1 month after vaccination
40
What is the overall rate of metastasis for FISS? (Hartman JFMS 2015)
10-28%
41
What other treatment besides sx/RT may improve prognosis for cats with FISS? (Hartmann JFMS 2015)
recombinant IL-2
42
**\*\*Which IHC markers are FISS positive for? (Carneiro, JFMS 2019)\*\***
* 100% positive for vimentin * 95.2% positive for S-100 protein * 19% positive for c-kit * 61.9% positive for COX-2 * 42.9% positive for FeLV particles
43
**\*\*Which IHC markers are FISS negative for? (Carneiro, JFMS 2019)\*\***
81% negative for desmin
44
PFI interval for cats with FSS treated with finely fractionated (48 or 52.8 Gy over 4 weeks delivered in 12-16 fx) VS. coarsely fractionated (36 Gy over 3 weeks delivered in 6 fx) RT? (Rossi JFMS 2019)
PFI finely fractionated = 2000d., coarsely = 540d Not statistically significant difference b/w the two
45
**\*\*What was significantly associated with PFI for cats getting finely fractionated (48 or 52.8 Gy over 4 weeks delivered in 12-16 fx) VS. coarsely fractionated (36 Gy over 3 weeks delivered in 6 fx) RT for FISS (Rossi, JFMS 2019)\*\***
PFI significantly different between groups when only first-occurence cases included (finely did better 1430d vs. 540d) No stat sig difference in cats getting finely vs. coarsley fx RT that had multiple surgeries prior (fine 395d, coarse 233)
46
Under what circumstances has carbo been found to be effective against FISS? (Maxwell Vet Surg 2018)
*in vitro* - FISS cell lines showed time and dose-dependent responses that are within range of carbo beads
47
What was the MST for cats treated with epirubicin + surgery for FISS? (Bray, VCO 2016)
MST not reached, 80% still alive Three cats (14% had tumor recurrence)
48
What was the dosing schedule/amount for cats treated with surgery + epirubicin for FISS? (Bray VCO 2016)
Epirubicin 25mg/m2, 3 doses prior to surgery, 3 after
49
What was the clinical response to palladia for cats with FISS? (Holdermann VCO 2016)
no measurable response (and cats were treated at high dose - 3.25mg/kg EOD)
50
**Dysregulation of what oncogene contributes to FISS growth and survival? (Lawrence VCO 2011)**
**PDGFR**
51
**FISS tumor cell lines (one from tumor, one from lung met) showed growth inhibition and decreased phosphorylation of PDGFR when treated with what? What was the difference in the two responses? (Lawrence VCO 2011)**
**Masitinib** **Higher concentration (8.6 uM) needed for growth inhibition compared to decreased phosphorylation (0.4uM)**
52
What was the response rate and duration for cats treated for FISS with CCNU? (Saba VCO 2011)
RR 25%, median duration 82.5d.
53
**What was the dose of ifosfamide given to cats for FISS and how was it given? (Rassnick AJVR 2006)**
**900mg/m2 IV over 30min** **Fluid diuresis 18.3ml/kg/hr for 5hr and mesna at 20% of mg dose given before, 2 and 5 hours after**
54
**What was the ORR for cats with FISS treated with ifosfamide? (Rassnick AJVR 2006)**
**ORR 41% - 1 CR, 10 PR**
55
**What was the median response duration for cats treated with ifosfamide for FISS (Rassnick AJVR 2006)**
**70d.**
56
**What were the AEs associated with ifosfamide in cats treated for FISS (Rassnick AJVR 2006)**
**Acute tox - netropenia at 7d., 33% GI toxicity** **2 cats had nephrotox. and 1 cat developed pulmonary edema during diuresis**
57
What was the median OST for cats treated with surgery vs. surgery + doxo x4 for FISS? (Martano Vet J 2005)
median OST 1724, no difference between groups
58
What was correlated with neutrophil-to-lymphocyte ratio in cats with FISS (Chiti VCO e-pub 2019)
Tumor size, histologic pattern of tumor growth and histotype
59
Neutrophil-to-lymphocyte ratio, white blood cell and neutrophil counts were prognostic for what in cats with FISS? (Chiti VCO e-pub 2019)
Univariate: local recurrence and OST Multivariate only recurrence
60
**What IHC markers are FISS positive for? (Carneiro JFMS 2018)**
**Vimentin (100%)** **S-100 protein (95.2%)** **COX-2 (61.9%)** **FeLV viral particles (42.9%)** **Desmin (19%)** **c-KIT (19%)**
61
What IHC marker was significantly associated with the degree of inflammation in FISS? (Santelices J Comp Path 2018)
COX-2 expression
62
FISS with high degrees of anaplasia had higher/lower expression of COX-2 (Santelices J Comp Path 2018)
high anaplasia = lower COX-2
63
What matrix remodeling proteins were associated with invasiveness in FISS? What was prognostic for FISS in this study? (Porcellato Vet Path 2017)
MMP-2, 9, TIMP-2 Size of tumor measured after formalin (\>3.75cm) and MI (\>20)
64
**What is metformin and how has it been shown to inhibit cancer cell proliferation (Pierro Res Vet Sci 2017)**
**Oral hypoglycemic drug** **inhibits cancer cell proliferation by upregulation of AMPK +/- inhibition of mTOR**
65
**What was the outcome of FISS cell lines treated with metformin? (Pierro Res. Vet Sci. 2017)**
**Dose-dependent decrease in cell viability** **Cell death by flow = apoptosis or necrosis** **No inhibition of mTOR or phosphorylated mTOR on Westerns --\> mech of cell death is not mediated by mTOR inhibition**
66
A positive correlation was shown between ____ and tumor grade for FISS using a 3D chick embryo chorioallantoic membrane model? (Zabielska-Kocywas BMC 2017)
PCNA - may be better than Ki67
67
What percent of feline fibrosarcomas stain positive for c-kit? What was this correlated with (vet path 2009 Smith)
26% but majority have \<10% of cells stained Not correlated with grade, survival or if injection site associated
68
**What somatic alterations have been identified in p53 in FISS and how were these detected? Anything prognostic? (Banerji AJVR 2006)**
**sequenced p53 exons 5-9 for SNPs to detect heterozygosity** **LOH at p53 in 60% of tumors** **LOH (allelic deletion) associated with shorter time to recurrence and overall surivial**
69
**FISS with cytoplasmic/nuclear p53 staining had a shorter time to recurrence than those with cytoplasmic/nuclear p53 staining (Hershey, Vet Path 2005)**
**Cytoplasmic had shorter time to recurrence**
70
**What percent of FISS have mutated p53? (Hershey Vet Path 2005)**
**81%**
71
**What cats with FISS benefit from post-op finely fx RT vs. coarsely fx RT? (Rossi JFMS 2018)**
**Finely fx RT: 1st recurrence FISS (PFI 1430 for fine vs. 540d coarse)** **Coarsely: cats with multiple recurrences (PFI not different for fine (233 vs. coarse 395d)**
72
**What was the overall PFI for cats with FISS treated with definitive intent or palliative intent RT (Rossi JFMS 2018)**
Overall PFI 2000 days
73
What was the MST and PFI for cats treated with curative intent RT (Eckstein VCO 2009)
MST 43mo, PFI 37mo Most of these cases had clean margins
74
What was the MST and PFI for FISS treated with palliative RT for dirty margins or gross disease? (Eckstein VCO 2009)
MST 24mo, PFI 37mo
75
What was the rate of local tumor recurrence for FISS treated with min 3cm margin (Muller JFMS 2017)
38.1% (range 33-55% depnding on many factors) despite curative intent surgery
76
What was associated with tumor bed biopsies of cats undergoing curative intent surgery for FISS (Muller JFMS 2017)
Not containing tumor cells = lower rate of recurrence (30.5%) vs. if tumor cells present (76.2%)
77
What was the median post-op DFI and MST for cats undergoing curative intent surgery for FISS (Muller JFMS 2017)
DFI 21mo, MST 24mo
78
What was significantly associated with death from tumor-related reasons for cats treated with curative intent surgery for FISS? (Muller JFMS 2017)
Recurrent tumors = sig more likely to die from tumor compared to cats with de novo tumors
79
What was the relationship between clinical and CT measurements for FISS? (Ferrari VCO 2015)
CT dimensions larger - increasing difference with increasing tumor size
80
What factors were predictors for wound healing complications in cats undergoing wide excision of FISS on the trunk? (Cantatore Vet Surge 2014)
duration of surgery (which was influenced by tumor width and excision pattern - i.e. complex surgery)
81
What was the rate of local recurrence and metastasis for cats undergoing radical surgery with 5cm margins for FISS? (Phelps JAVMA 2011)
14% local recurrence 20% mets
82
What was the rate of major complications in cats undergoing radical surgery with 5cm margins for FISS? (Phelps JAVMA 2011)
10/91 had major complications (7 were incisional dehisence)
83
What was the survival time for cats with or without recurrence after 5cm radical excision of FISS (Phelps JAVMA 2011)
w/ recurrence 499d (only 14% of cats had recurrence w/o recurrence 1461d
84
What was the major conclusion from the FISS data from Switzerland (Graf J comp path 2018)
Marked decrease in FISS during 2009-2014 which occurred after a non-adjuvanted FeLV vax was introduced in 2007 Supports alum-adjuvanted vx involved in FISS development
85
What injections were more common in cats with interscapular FISS compared to control cats? (Srivastav JAVMA 2012)
long-acting corticosteroids
86
For cats with rear leg FISS, it was less likely that they recieved ____ rabies vaccines (Srivastav JAVMA 2012)
recombinant rabies vaccine (i.e. more likely to have had inactivated rabies vaccines)
87
**Cats from 1990 to 2006 showed a decrease of FISS in the _____ region and an increase incidence in the \_\_\_\_\_\_. (Shaw JAVMA 2009)**
**Decrease Interscapular region, increase in right lateral abdomen**
88
What two injectable medications are more common in cases of FISS than in control cats? (Kass JAVMA 2003)
penicillin and methylprednisolone
89
What was the average number of mm infiltrated on dynamic CT (double positioning CT) (Longo JFMS 2017)
1.84-1.9, sumors with smaller volumes showed slightly decreased mm infiltration
90
How successful was CT angiogram and MR at distinguishing neoplastic vs. nonneoplastic peritumoral lesions from FISS? (Nenmanic Vet Surg 2016)
MR and CT angio cant' distinguish the two (~4 peritumoral lesions were detected/cat, 59% were nonneoplastic)
91
What are the ultrasound features of recurrent and non-recurrent FISS? (Zardo, JFMS 2015)
irregular tumor margins hyperechoic rim heterogenous echotexture hyperechoic adjacent tissue thickening of adjacent SQ tissue
92
What are the CT findings for cats with FISS? (Zardo JFMS 2015)
Irregular shape with digitform projections, mixed contrast enhancement, blurring of fat planes, liquefactive intratumoral necrosis
93
Were FISS smaller or larger on MRI compared to CTA? Fleming VRU 2019); what about higher grade FISS copared to lower grade?
FISS generally larger on MRI compared to CTA Higher grade FISS larger than low grade FISS on MRI