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Onco Board Review 2 > TCC/Urinary/Prostate > Flashcards

TCC/Urinary/Prostate Flashcards

1
Q

What is T1 TCC?

A

superficial papillary tumor

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2
Q

What is T0 TCC?

A

no evidence of primary tumor

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3
Q

What is T2 TCC? What % have T2 tumors at presentation?

A

tumor invading bladder wall, with induration

78%

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4
Q

What is T3 TCC?

A

tumor invading neighboring organs (prostate, uterus, vagina, pelvic canal)

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5
Q

What % of dogs had distant TCC mets at necropsy? What % have mets at presentation?

A

58%; 20%

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6
Q

Which breeds are at increased risk of TCC?

A

Scotties (21-fold); Eskimo dogs, Shelties, Westies, Keeshonds, Samoyeds, Beagles (3-6.5-fold)

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7
Q

What exposures have been linked to TCC?

A

old flea/tick products, lawn chemicals, possibly cyclophosphamide

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8
Q

What may have protective benefit for TCC?

A

Feeding vegetables 3x per week (carrots were most common)

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9
Q

What % of TCC were successfully diagnosed with cystoscopy/biopsy in female dogs? Male dogs?

A

female - 96%

male - 65%

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10
Q

What IHC can help distinguish TCC from other poorly differentiated carcinomas?

A

uroplakin III (UPIII)

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11
Q

Uncommon site of TCC metastasis?

A

Skin - erythematous, ulcerative, proliferative lesions

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12
Q

In a recent Purdue report, what % of dogs that had undergone surgery for TCC had spread to abdominal wall? What was MST for these dogs after detection of the mets?

A

10.2%

MST 57 days

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13
Q

What complication is common after stent placement?

A

incontinence, 26-39% of dogs

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14
Q

What is the ORR of TCC to piroxicam? SD? MST?

A

21%, SD 59%, MST 244d (8 mo)

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15
Q

What is the ORR of TCC to deracoxib? SD? MST?

A

17%, SD 71%, MST 323d (10.7mo)

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16
Q

What is the ORR of TCC to mito/piroxicam? SD? MST?

A

35%, SD 46%, MST 291d (9.7mo) (from Henry 2003)

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17
Q

What is the ORR of TCC to VBL? SD? MST? (Arnold JVIM 2011)

A

36%, SD 50%, MST 147d (4.9mo)

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18
Q

What is the ORR of TCC to carbo/piroxicam? SD? MST?

A

38%, SD 45%, MST 161d, (5.4mo)

Note that ORR for carbo alone was 0% in Chun 1997

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19
Q

What is the response to firocoxib? What about when combined with cisplatin?

A

20%

Combined with CIS - 57% (CIS was 13% as single agent)

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20
Q

Intravesical mitomycin C has been used to treat TCC. What were the results (response, toxicity)?

A

5/13 partial remission, 7/13 SD

severe myelosuppression and GI AEs

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21
Q

Response (PR and SD) to metronomic chlorambucil? (Schrempp 2013)

A

3% PR, 67% SD; most had failed previous tx

PFS 119d, MST 221d

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22
Q

75% of TCCs in dogs have high intake of what?

A

folate - recent push for folate-targeted therapy

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23
Q

What enzyme involved in methylation is over expressed in canine TCC?

A

DNMT1

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24
Q

What was PR and SD with 5-aza (de-methylating agent)? What was dose limiting AE? (Hahn 2012)

A

PR 22.2%; SD 50%

Neutropenia was dose limiting

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25
What oral de-methylating agent may be useful for TCC given the results with 5-aza?
zebularine
26
What are 4 risk factors for TCC development?
female sex, obesity, neutering, chemical exposure
27
What is the OR of a Scottie developing TCC?
18.09
28
T/F: The bladder tumor antigen test is very specific.
False - sensitive but not specific
29
What is lapatinib? How did it affect TCC cell lines? (Sakai 2018)
TKI that inhibits HER2; inhibited HER2 signaling and induced cell cycle arrest (inhibited growth in concentration-dependent manner); also shrunk tumors in nude mice
30
What % of dogs have UTIs during chemo tx for TCC?
55%; staph and e.coli were most common
31
What is the CR to piroxicam? To deracoxib?
6%; 0%
32
T/F: Metastatic disease to the kidneys is more common than primary tumors?
True
33
What is the overall MST for dogs with various renal tumors undergoing nephrectomy?
16mo
34
What is the MST for dogs treated for renal HSA?
278d (9.3mo)
35
What genetic mutation predisposes people to RCC?
VHL (von Hippel-Lindau)
36
What was the overall median PFI and MST for partial cystectomy (with various post-sx treatments)? (Marvel 2017)
``` PFI 235d (7.8mo) MST 348d (11.6mo) ```
37
What was the overall MST for partial cystectomy with daily piroxicam (with or without chemo)? (Marvel 2017)
772d (2.1 yrs)
38
What % of dogs had PR + SD with metronomic chlorambucil for TCC?
70% Only one had PR, they used WHO criteria Could only have COX inhibitor for pain management if TCC had previously been progressing on COX inhibitor (in an attempt to avoid compromising results) Used cystosonography to objectively evaluate tumor size.
39
Low ___ was correlated with vessel invasion, metastasis, and decreased survival? p63 vs. Ki67 vs. B-catenin
p63 | this is a member of the p53 family of transcription factors
40
What % of TCC are HER2 positive?
56% | significantly over-expressed in neoplastic vs. non-neoplastic (but only looked at 23 TCC and 5 non-neoplastic)
41
What two histopath features were correlated with outcome for canine RCC? (Carvalho 2017)
MI > 30 and COX-2 score > 3 were both correlated with shorter MST.
42
Which of the following are expressed in TCC: PDGFR-B, VEGFR2, KIT? (Walters 2018)
PDGFR-B expressed in more TCC samples than normal bladder and cystitis. All tumors positive for VEGFR2, but so were non-neoplastic samples. Minimal KIT staining in tumor samples.
43
In a recent prostatic carcinoma study, what was the overall TTP and MST? (Ravicini 2018)
TTP 63 days | MST 82 days
44
In a recent prostatic carcinoma study, what was the overall TTP and MST for those treated with NSAID + chemo? (Ravicini 2018)
TTP 76 days | MST 106 days
45
What gene/proteins are down-regulated in prostatic carcinoma? (Rivera-Calderon 2016)
PTEN, p53, AR down-regulated. | MDM2 over-expressed (inhibits p53)
46
What type of renal carcinoma is associated with a worse prognosis? (Edmondson 2015)
Clear cell carcinoma
47
What histopath marker correlates with outcome for feline RCC? (Bommer 2012)
COX-2; MST for (+) = 123d, MST for (-) = 375d
48
Does combination VBL/TOC improve survival for TCC? (Rippy 2016)
Nope
49
Does hedgehog signaling play a role in TCC proliferation? (Gustafson 2015)
Yes
50
What % of female dogs with TCC have UTI at some point? (Budreckis 2015)
80% (vs. 29% male)
51
Results of intra-arterial carbo for lower urinary tract carcinoma? (Culp 2015)
more likely to have anti-tumor response and less likely to have anemia, lethargy, anorexia
52
What % of dogs needed piroxicam to be discontinued in the phase III comparing mito/pirox to carbo/pirox? (Allstadt 2015)
32% | secondary to GI signs was most common reason
53
In a phase III trial, was there a difference between mito vs. carbo (both with piroxicam)? (Allstadt 2015)
No | also note that there were no CRs
54
Response rate of TCC to vinorelbine in rescue setting? (Kaye 2013, Lawrence senior author)
14% PR 57% SD Subjective improvement in clinical signs in 78%
55
What was PR and SD with DOX/piroxicam combination protocol? (Robat 2013)
PR 9%, SD 60.5% -- based on AUS | 50% of dogs had surgery before chemo in this study, 23/34 had measurable dz at chemo onset
56
In the Knapp 2013 comparison of cisplatin vs. firocoxib vs. cisplatin/firocoxib, why did they choose firocoxib?
Selective COX-2 inhibitor; hypothesized that it would be more protective against renal effects (fewer COX-2 receptors in kidney than COX-1)
57
What % PR and SD were induced by firocoxib? (Knapp 2013)
PR 20%, SD 33% Utility as single agent. Firocoxib also significantly enhanced activity of cisplatin but renal effects inherent to cisplatin were still a problem.
58
What was the subjective response to IM/IGRT (54-58 Gy total) for genitourinary carcinomas? (Nolan 2012)
60%
59
What was the overall MST to IM/IGFR (54-58 Gy total) for genitourinary carcinomas? (Nolan 2012)
654d (event-free survival was 317d) | Neoadjuvant therapy was not standardized!!! Dogs had mixed bag of NSAIDs, MTD chemo, and surgery before RT.
60
What % had improved clinical signs in response to 6 x 5.75 Gy hypofractionated RT combined with mito/piroxicam? (Poirier 2004)
90% improved signs PR was 22% MST was 326 days Conclusion - not superior to chemo alone
61
What was COX-1 and COX-2 expression in cats with TCC? How did this affect survival? (Bommer 2012)
7/7 COX-1, 5/7 COX-2 | COX-2(+) had shorter survival (123d vs. 375d)
62
What was the response to 10 x 2.7 Gy for Canine TCC (CR and PR)? ORR? (Choy 2016 VRU)
7.6% CR, 53.8% PR ORR 61.4% Occurred within 6 weeks of radiation MST from start of RT 150d (5mo)
63
Activating mutations of BRAF lead to constitutive activation of the ____ pathway.
MAPK
64
What % of urothelial/prostatic carcinomas have the BRAF V595E mutation?
~80% per original publication
65
What was the sensitivity for droplet digital PCR to detect urothelial carcinoma and prostatic carcinoma? What 0% of control samples were mutation positive?
UC - 75% PC - 85% Control - 0%
66
Sanger sequencing requires a ___ - ___% fraction of mutated allele for reliable detection.
10-20%
67
What is the gold standard test for detecting a single nucleotide substitution?
Sanger sequencing
68
What was the sensitivity and specificity of urine ddPCR to detect BRAF V595E in urine samples?
Sn 85%/ Sp 100%
69
What was dose of VBL used for TCC? (Arnold JVIM 2011)
3 mg/m2 q2 wks | 61% required dose reduction due to neutropenia
70
What was RR and clinical remission duration for cats with small cell GI LSA treated with pulse chlorambucil (every other week)? (Stein JAAHA 2010)
Clinical response 96% (resolution of c/s) | Remission duration 786d (2.15yr)
71
What % of dogs with TCC have nodal and distant metastasis at dx?
16% nodal, 14% distant
72
What % of prostatic carcinomas express COX-2?
75-88%
73
T/F: Intact males with prostatic mineralization are likely to have cancer.
False
74
T/F: Most canine bladder tumors are T1.
False
75
What is the MST for dogs with prostatic carcinoma treated with an NSAID?
6.9 months
76
Which TCC treatments have been reported to induce a CR?
1. piroxicam alone 2. mito/piroxicam 3. gem/piroxicam 4. cisplatin/piroxicam
77
What unexpected side effects were seen with intravesicular mitomycin C?
marked myelosuppression and GI upset
78
T/F: Metastatic disease to the kidneys is more common than primary renal tumors in dogs.
True
79
What is the most common primary renal tumor in a dog?
Renal cell carcinoma
80
What genetic mutation predisposes people to RCC?
Von Hippel-Lindau gene mutation | rare in canine RCC
81
Which breeds are predisposed to prostatic carcinoma?
Doberman, Bouvier des Flandres, Beagle, Airedale
82
What % of dogs with prostatic carcinoma have skeletal metastasis?
22-42% (lumbar vertebrae, pelvis predominantly)
83
What is the general MST for dogs with prostatic carcinoma with no treatment?
< 30 days | 0.7 months
84
What is the MST for dogs with prostatic carcinoma treated with mito/pred? (Hazzah 2013)
5.1 months (155d)
85
What was the MST for renal Hemangiosarcoma (dogs undergoing nephrectomy and chemo)? (Locke 2008)
278d (9 months) | - worse for dogs with hemoperitoneum, mets
86
What % of dogs have positive urine culture at diagnosis of TCC? (Budreckis 2015)
25%
87
Increased risk (odds ratio) for neutered males for the following? (Bryan 2007, supplemental reading) - bladder TCC - prostate TCC - prostatic adenocarcinoma - prostate carcinoma - all prostate cancers
- bladder TCC: 3.56 - prostate TCC: 8.00 - prostatic adenocarcinoma: 2.12 - prostate carcinoma: 3.86 - all prostate cancers: 2.84
88
In the 2005 paper, was COX-2 and/or PGE2 expression predictive of response to piroxicam (Mutsaers 2005)
No

Onco Board Review 2 (20 decks)

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