STS/FISS Flashcards by Megan S

What 3 parameters are used to grade STS?

differentiation
MI (0-9, 10-19, >20)
% necrosis (none, <50%, >50%)

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What is the met rate for oral high-low FSA?

up to 20%

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What is the met rate for dermal smooth muscle tumors?

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Which is not a common location for rhabdomyosarcoma?

a. urinary bladder
b. larynx
c. digit
d. tongue
e. myocardium

Digit

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T/F: Lipomas, intramuscular lipomas, infiltrative lipomas, and liposarcomas all appear similar cytologically but vary with regard to invasion/metastasis.

False
Lipomas - indistinct nuclei, cytoplasm resembling normal fat
Liposarcomas - increased cellularity, distinct nuclei, abundant cytoplasm with on or more droplets of fat

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What STS are hormone dependent?

Leiomyomas of the vagina and vulva

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How does risk of metastasis differ for leiomyosarcomas of the liver, intraabdominal, and dermal smooth muscle? What are most common sites of spread?

liver - 100% metastasized in one case series
intraabdominal - 50% metastasis
dermal smooth muscle - 0% metastasis

Sites: regional LN, mesentery, liver

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Which IHC stains differentiate synovial cell sarcoma from histiocytic sarcoma?

Synovial: vimentin and cytokeratin
HS: CD18, CD204 (CD18 is sarcoma, CD204 specific among leukocytes for histolytic origin)

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What prognostic factors have been identified for synovial cell sarcoma?

Grade
Clinical stage
Extent of surgical treatment

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How does MST differ for different grades of synovial cell sarcoma?

Grade 1: MST 48 mo
Grade 2: MST 36 mo
Grade 3: MST 7 mo

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How does MST differ for clinical stage of synovial cell sarcoma? For amp vs. no amp?

Stage: LN mets <6 months, No LN mets >36 months
Amp: MST 850d, No amp: MST 455d

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What % of dogs with synovial cell sarcoma have metastasis at time of diagnosis?

32%

54% at time of death - but this source may be pre-identification of periarticular HS

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What is the staging scheme for STS?

Stage I: grade I or II, any size, any depth, N0, M0
Stage II: grade III, tumors <5cm any depth, tumors >5cm superficial only, N0, M0
Stage III: grade III, tumors >5cm, N0, M0
Stage IV: any grade, any size, any depth, N1 or M1

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What is the recurrence rate of grade I, II, and III K9 STS after incomplete excision? (Dennis Vet Path 2011)

Grade I: 7%
Grade II: 34%
Grade III: 75%

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What is the overall MST for K9 incompletely resected non-oral STS treated with post-op RT?

2270d (6.2y)
Only 540d for oral sarcomas
(control rate 80-95% at 1 year)

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What is the reported 1 year tumor control rate for K9 STS treated with dRT alone?

1 year: 50% control
2 year: 33% control
50Gy dose

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What is the RR to pRT for K9 STS? Median time to progression?

50% RR
32 Gy dose
Median time to progression 155d
MST 309d

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What is the median time to metastasis in K9 STS?

365d, occurs late in course of disease

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What is the RR of K9 STS to DOX +/- CTX?

23%

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The development of FISS at vaccination site is believed to be as high as?

1/1000

other reports as few as 1/10,000

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IHC evaluation of ISS identified expression of:

PDGF
EGF and it’s receptors
TGF-beta

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Lymphocytes in ISS are positive for what growth factor?

PDGF

Lymphocytes in non-injection site fibrosarcomas and normal LN are negative

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T/F: p53 mutations have been identified in ISS.

True

Anti-p53 antibodies have immunoreactivity in feline sarcomas and may play a role in predicting outcome

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What is the median TTR following marginal resection of FISS?

79d

66d when surgery is with rDVM

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What is the median TTR following radical surgery of ISS?

325-419d

What % of patients had major surgical complications after removal of an ISS with 5cm lateral margins and two fascial planes deep? What % had local recurrence?

11% complication rate 14% recurrence 97% complete resection

What % of ISS recur after surgery and pre-op RT?

40-45% recurrence at median of 398-584d

What % of ISS recur after surgery and post-op RT? What about with addition of DOX?

``` 41% recurrence at median of 405d With DOX (and sx/RT): 28% recurrence at median of 661d ```

What is the reported MST for cats treated with surgery and RT for FISS?

600-1300d

What is the RR to DOX+/- CTS in macroscopic FISS?

39-50% RR | Median duration of 84-125d

What is MST for FISS cats that respond to chemo vs. not?

Responders: 242d | Non-Responders: 83d

What % of histopath reports (in recent retrospective study) included microscopic description for STS? What about measured margins?

Only 64.8% gave description and 59.6% gave margins! Useless.

What was DFI for treated vs. control dogs in CTX/piroxicam study? (Elmslie 2008)

Control - 211d | Tx - 410d

What dose of CTX/piroxicam was used in original STS study? What % developed SHC? (Elmslie 2008)

CTX 10 mg/m2, piroxicam 0.3 mg/kg | 10% SHC

Did doxorubicin provide a survival benefit for high grade STS? What was % local recurrence and metastasis? (Selting 2005)

No benefit | 23% recurrence, 44% metastasis

What were the imaging features of PNST on MRI? (2007)

T1 - hyperintense | T2 - isointense

What were findings of STS on PET scan using hypoxia tracer? What was the tracer? (Bruehlmeier 2005)

hypoxia noted in 3/6 tumors with low perfusion | tracer was 18F-fluoromisonidazole (FMISO)

What were the locations of rhabdomyosarcoma in horses? What were the types? (Castleman 2011)

4 tongue or head, 2 abdominal wall, 1 shoulder mm, 1 heart Types - 7 embryonal, 1 pleomorphic (4 treated with surgery or RT with no recurrence)

What were results of RT + DOX for incompletely excised feline STS? (Hahn 2007)

DFI with DOX longer (15.4mo) than w/o (5.7mo); no difference in survival (tumor grade/histo not reported)

What IHC markers were positive for feline PNST? Did they met? (Schulman 2009)

Positive for vimentin and S-100, majority positive for GFAP All negative for SMA No metastasis documented

What were prognostic factosr for cats treated with surgery and RT for STS? (Mayer 2009)

Anemia (PCV < 25% 308d vs. > 25% 760d) | Timing of RT (post-op did better than pre-op - pre-op may have been bigger tumors not amenable to sx)

What IHC marker confirmed dx of liposarcoma in cases that were not well-differentiated? (LaDoucer 2017)

Oil red O (confirmed lipid) | Previous studies also showed that this stains liposarcomas and not others

What protein correlated with grade and may be a diagnostic/prognostic marker for liposarcoma? (2016)

MDM2

How did MI affect survival time for canine STS in Dennis Vet Path 2011?

MI > 9 - 150-343d | MI < 9 - 826-1138d

Intratumoral microvessel density increases with ___, ___, and ___. (Luong 2006)

grade, necrosis, mitotic score | also correlated with AgNOR and increased metastasis

What two parameters correlated positively with grade and MI in Ettinger JAVMA 2006?

AgNOR and Ki67 | on multivariate analysis, increased AgNOR prognostic for decreased survival

What was response to hypofractionated RT for macroscopic STS? (Cancedda 2016)

ORR 30%, BR 100%; 10% CR, 20% PR, 70% SD; OST was 513d | note: no controls, some dogs had metronomic chemo, 50% grade 1 STS

What was % local recurrence and metastasis with hypofractionated RT for microscopic STS? (Kung 2014)

21% local recurrence, 23% metastasis (total was 24-32 Gy) | 50% were grade 2

Lawrence JAAHA 2008 - What was ORR, TTP, and OST for macroscopic STS treated to 32 Gy?

``` ORR 50% (7 PR, 1 CR) TTP 155d (5 mo) MST 309d (10.3mo) ```

What was the % local recurrence of STS managed in first opinion practice? (Bray 2014, Chase 2009)

Bray - 20.8% - extent of resection not associated with survival, probable bias for less aggressive tumors Chase - 27.9%

What % of residual tumor was identified in re-cut of incompletely excised STS? What was local recurrence and metastasis after re-cut? (Bacon 2007)

22% residual tumor | local recurrence 15%, metastasis 10%

What was recurrence and metastatic rate for low grade spindle cell sarcoma at or distal to elbow treated with marginal excision? (Stefanello 2008)

10.8% recurrence | 0% metastasis

The volume of FISS based on CT is often ___x caliper measurements.

Beads implanted with what chemo showed 50% growth inhibition in FISS cell lines?

carboplatin

What adjuvant has been implicated in FISS?

aluminum

What was median DFI and MST following en bloc resection of FISS with 3cm margins? % tumor recurrence?

DFI 21 months MST 24 months 38.1% recurrence

For cats undergoing RT for microscopic FISS, how did PFI differ for finely fractionated (48-52.8 Gy) vs. coarsely fractionated (36 Gy)? (Rossi 2019)

For cats treated after removal of first-occurrence FISS, median PFI was significantly longer in finely fractionated group (1430d vs. 540d). (it did not differ for cats who had undergone multiple surgeries)

In a recent study, what IHC markers were positive for FISS? (Carneiro 2018)

desmin, vimentin, S-100 (95.2%), c-KIT, COX-2, and FeLV viral particles (note that, per Withrow, FeLV was NOT detected but was in this study)

What % of recut STS (original incomplete margins) had residual tumor? (Bacon 2007)

22%

What was FISS local recurrence with lateral surgical margins of 3cm and body wall resection/2 fascial planes deep?

38.1%! Yikes.

Does masitinib enhance radiosensitization of FISS cells? (Turek 2014)

What % of cats with FISS had objective response to SBRT? What was the median PFS and MST? (Nolan 2013)

``` 72.7% response (8/11 cats) - varied whether this was CT vs. PE PFI 242d (again, not all had CT), MST 301d ```

Are there any vaccines that are risk-free for FISS? (Srivastav 2012)

Does masitinib have anti-proliferative effect on FISS cells? What receptor was evaluated? (Lawrence 2012)

Yes - inhibits cell growth and PDGFR phosphorylation in both primary and metastatic FISS (in vitro).

What anti-angiogenic agent was used in canine STS? What was RR and unique side effects? (Sahora 2002)

thrombospondin-1 mimetic peptides 23% RR Keratitis and OA were dose-limiting toxicities

What was the effect of Toceranib for FISS? (Holtermann 2016)

No clinical response measurable in n=18 | tx with 3.35 mg/kg EOD

What was the concordance in grade between pre-treatment biopsy and excisions biopsy for STS? (Perry 2014)

59% | For the 41% that didn't agree 29% of pre-treatment biopsies underestimated the grade

What were the results of CCNU to treat FISS? Concerns regarding AE? (Saba 2012)

ORR 25%, PFS 60.5d; median duration response 82.5d Significant hematologic toxicity (target dose 38-60 mg m(-2) q3 weeks, lots of delays and reductions)

What % of cats had PR to liposomal doxorubicin and pRT? CR? (from intro in Holtermann 2016)

50% PR | 20% (2/10) CR

What is the expression of KIT in feline injection site sarcoma? (from intro in Holtermann 2016)

Only 9% of samples had >80% immunoreactivity for KIT - concluded that other factors likely contribute to dz progression

T/F: More than half of the peritumoral lesions identified on advanced imaging were deemed nonneoplastic after microscopic evaluation, and 20% of lesions were confirmed neoplastic.

True (Nemanic VSx 2016)