Caner of the GI tract: AGASACA/peri-anal tumors

Question 1

What breeds are predisposed to developing perianal adenomas? (n=4). Which breed is predisposed in both sexes?

Answer 1

• Cocker Spaniels, Beagles, Bulldogs, Samoyed
• Cocker spaniels

Question 2

Male dogs show a ___ - fold increased risk compared to females for the development of perianal adenoma.

Answer 2

5.6-fold

Question 3

***A retrospective study of 43 dogs with early-stage (<3.2cm), non-metastatic AGASACA treated with surgery alone reported a MST of _____, local recurrence of ___% at a median of _____, and a metastatic rate of ___% at a median of ____. _______ was positively associated with development of metastatic disease and no other factors were associated with outcome.

Answer 3

• MST: 41mo
• LR: 20% at median of 12mo
• Met: 26% at median of 20mo
• cellular pleomorphism

Question 4

A retrospective study evaluated prognosis based off stage of AGASACA. Stage 1 was associated with a MST of ____ - ____. Stage 2 was associated with a MST of ____ - ____, stage 3a was associated with a MST of ___-____, stage 3b was associated with a MST of ____-_____, and stage 4 was associated with a MST of ___-____.

Answer 4

• Stage 1 MST: 40mo - not reached
• Stage 2 MST: 24mo - not reached
• Stage 3a: MST 15-16mo
• Stage 3b: MST: 10-11mo
• Stage 4: MST 2-3mo

Question 5

***A retrospective study of 74 dogs treated with surgery +/- adjuvant carboplatin reported an oMST of ____ and TTP of ____. No significant difference in OS and TTP between dogs that received adjuvant carboplatin and those that did not. Only ______ and ______ at diagnosis significantly affected outcome and ______ prolonged survival. PFI for surgery alone was ____, and MST was ______. PFI for surgery and carboplatin was _____ and MST was _____.

Answer 5

• oMST: 23mo
• TTP: 13mo
• primary tumor size and lymph node metastasis
• treatment of progressive disease

PFI
- surgery alone: 13mo
- surgery + carbo: 13mo

MST
- surgery alone: 19mo
- surgery + carbo: 24mo

Question 6

What is the rate of metastasis at diagnosis for dogs with perianal adenocarcoma?

Answer 6

15%

Question 7

Serum _____ levels were found to be higher in dogs with malignant perianal tumors than those with benign tumors.

Answer 7

magnesium

Question 8

What IHC markers may help differentiate perianal adenoma from adenocarcinoma?

Answer 8

carcinoma-associated antigens A49, 1A10, PCNA, and Ki67

Question 9

Electrochemotherapy for perianal adenomas has a ORR of ___% and CR rate of ___%.

Answer 9

ORR: >90%
CR: 65%

Question 10

In a series of 41 dogs with perianal adenocarcinoma, tumors ____ cm had a 2-year control rate of ___% with surgery. Metastasis was a poor prognostic factor for survival. For dogs with LN or distant metastasis, MST was _____. In a smaller study, tumor recurrence was ___%.

Answer 10

• <5cm
• 2 year control rate: >60%
• MST met: 7mo
• 75%

Question 11

What are the predisposed dog/cat breeds for AGASACA? n=5

Answer 11

English cocker spaniels, GSDs, Alaskan malamutes, and dachshunds

Siamese

Question 12

The incidence of bilateral AGASACAs, either simultaneously or temporally separated is ___%.

Answer 12

14%

Question 13

Paraneoplastic hypercalcemia occurs in ___-___% of dogs with AGASACA.

Answer 13

16-53%

Question 14

***The metastatic rate at diagnosis in dogs with AGASACA is ___-___% with regional lymph node metastasis being present in ___-___% and distant sites ___-___%

Answer 14

• 26-96%
• RLN: 26-89%
• Distant: 0-42%

Question 15

In a case series of 11 dogs with anal sac melanoma treated with various combinations of surgery, RT, chemotherapy, and supportive care, sublumbar metastasis at diagnosis was found in ___% and pulmonary metastasis at ___%. ____% of dogs died due to tumor progression. PFI was ____ and MST was ____.

Answer 15

• RLN: 50%
• Pulmonary: 9%
• 90%
• PFI: 3mo
• MST: 4mo

Question 16

For 9 dogs with SCC of the anal sac, tumor recurrence after surgery was ___%, which occurred <6mo after surgery, and ___% of dogs staged at diagnosis had metastasis.

Answer 16

• LR: 80%
• Met: 0%

Question 17

The metastatic rate for feline AGASACA at diagnosis has been reported to be ___% to regional lymph nodes. Paraneoplastic hypercalcemia was reported in ___%.

Answer 17

• RLN: 20%
• hypercalcemia: 11%

Question 18

A small study of cytokeratin immunoreactivity in perianal tumors showed a repeatable pattern of expression in AGASACA of _____.

Answer 18

CK7+/CK14-

Question 19

***The sacral lymph node was deemed the sentinel lymph node in ___% of cases with AGASACA.

Answer 19

25%

Question 20

The complication rate after local excision of AGASACA ranges from ___-___% and ___-___% for lymph node extirpation.

Answer 20

• local: 5-25%
• LN: 0-12%

Question 21

***In a study of 113 dogs with AGASACA, no significant difference in outcome between dogs treated with surgery alone and dogs treated with surgery and chemotherapy. The MST for surgery alone was ____ and ____ for surgery and chemotherapy.

Answer 21

MST:
- Surgery alone: 17mo
- chemotherapy + surgery: 18mo

Question 22

***Palladia has modest tumor responses for canine AGASACA. In a retrospective study of 32 dogs with multiple failed prior therapies, tumor response durations with Palladia ranged from ___-___, PR was ___%, SD was ___% for an overall clinical benefit of ___%. Anti-tumor effect likely mediated through _____ and ______.

Answer 22

• response durations: 3-12mo
• PR: 25%
• SD: 63%
• CB: 88%
• PDGFRb or VEGFR-2

Question 23

Radiation therapy measurable response for bulky disease of AGASACA ranges from ___-___%.

Answer 23

38-75%

Question 24

In a study of 113 variably treated dogs, use of adjuvant RT did NOT result in significant improvement in STs in 15 dogs. MST was longest among the treatment groups at ____.

Answer 24

25mo

Question 25

In a report of standardized curative-intent adjuvant RT (15 x 3.2Gy to primary tumor and regional LNs) in combination with mitoxantrone, MST of 15 dogs was ____. Late complication rate was ___%.

Answer 25

- MST: 32mo - Late complication: 50%

Question 26

***Late radiation effects, such as rectal stricture, rectal perforation, and chronic colitis, are more likely to occur when radiation doses per fraction of _____ are used in definitive protocols.

Answer 26

>/= 3Gy

Question 27

For palliative-intent protocols of canine AGASACA, improvement in clinical signs are seen in ___%. Hypercalcemia is reported to resolve with RT alone in ___% and when RT is combined with prednisone and bisphosphonates at ___%. Median PFI ranges from ___-___, and MST range from ___-___. Late effects are rare with a reported rectal stricture rate of ___% and occur in dogs treated with fractions of ____ or greater.

Answer 27

- 63% - 31% - 46% - PFI: 10-11mo - MST: 8-15mo - rectal stricture: 3% - > / = 5Gy

Question 28

For dogs treated with surgery +/- adjuvant therapy for canine AGASACA, DFI ranges from ___-___. Local recurrence rate is __-___%, which is/is NOT associated with completeness of excision?

Answer 28

- DFI: 9-15mo - LR: 5-44% - Is NOT

Question 29

Multiple studies have reported a shorter median DFI in dogs with LN metastasis from AGASACA, ranging from ____-____. The hazard of disease progression is ____- fold if LN metastasis is present. For dogs with no LN metastasis, DFI ranges from ____-____. ***In other studies, dogs treated with surgery +/- adjuvant chemotherapy, LN metastasis had a significant negative impact on survival time with MST of ____-____ for dogs with LN metastasis and ___-____ for dogs without.

Answer 29

- DFI LN met: 5-7mo - 2.5-fold - DFI no LN met: 18-25mo - MST LN met: 10-15mo - MST no LN met: 18-31mo

Question 30

In a study of 74 dogs with AGASACA treated surgically +/- adjuvant chemotherapy, local recurrence and/or LN metastasis occurred in ___%. If recurrent or metastatic disease was treated, MST was ____ after treatment for PD. If recurrent or metastatic disease was NOT treated, MST was ____. In another study, additional MST associated with second surgery was ____.

Answer 30

- 55% - MST tx: 13mo - MST no tx: 2mo - MST sx: 9mo

Question 31

***In one study, dogs with NO metastasis and primary tumor size <2.5cm treated with surgery alone had favorable outcomes with MST of ____ and tumor-related deaths in ___%.

Answer 31

- MST not reached - 9%

Question 32

***In a study of 28 dogs with advanced LN metastasis (>4.5cm), treatment with hypofractionated RT resulted in better median PFI and MST than surgery and LN extirpation. The PFI for RT dogs was _____ and ____ for surgery dogs, and the MST was ____ for RT dogs and _____ for surgery dogs.

Answer 32

PFI - RT: 12mo - sx: 5mo MST: - RT: 15mo - sx: 6mo

Question 33

***A maximal tumor dimension of 2.5cm was found to be prognostic for non-metastatic tumors. MST for tumors <2.5cm was ____, and _____ for tumors >2.5cm.

Answer 33

MST - <2.5cm: 3.3 years - >2.5cm: 24mo

Question 34

***Dogs with AGASACA treated with surgery have a significantly better outcome. One study reported a MST of ____ with surgery, ____ with chemotherapy alone, and _____ when surgery was NOT part of the treatment.

Answer 34

MST: - sx: 18mo - chemo alone: 7mo - sx NOT apart of tx: 13mo

Question 35

Expression of E-cadherin in >75% of cancer cells was associated with a longer MST for dogs with AGASACA (_____) compared to those with expression <75% (____).

Answer 35

MST - >75%: 3.2 years - <75% 15mo

Question 36

***Feline AGASACA treated with surgery +/- adjunctive chemotherapy and/or RT reported a DFI of ____, MST of ___, LR of ___% at a median of ___, and 1-year survival rate of ___%. ____ was the most common life-limiting event. _____ and _____ were poor prognostic factors.

Answer 36

- DFI: 8mo - MST: 9mo - LR: 37% - 1 year: 42% - LR - local recurrence and increased nuclear pleomorphic score

Question 37

Risk of tumor-related death for cats with AGASACA is ___x with recurrence and ____x for cats with increased nuclear pleomorphic score. A score of 2 resulted in MST of ____ and a score of 3 resulted in a MST of ____.

Answer 37

8x 10x MST - Score 2: 30mo - Score 3: 6mo

Question 38

A recent study evaluated the proportion of dogs with AGASACA that have tumors <2cm and LN metastasis at presentation. The LN metastatic rate for dogs with small tumors (<2cm) was ___% compared to those with tumors >/= 2cm at ___%.

Answer 38

<2cm: 20% >/=2cm: 63%

Question 39

A recent study of 57 dogs with AGASACA and RLN metastasis treated with sacculectomy and lymphadenectomy evaluated prognostic factors regarding the metastatic LNs. They found that the number of metastatic lymph nodes was associated with outcome but not size of the lymph nodes. A number of _____ was associated with shorter PFI, TDP, and DSS. The PFI was ___, the TDP was ___, and the DSS was ____.

Answer 39

- >4 metastatic LNs: decreases outcome - PFI: 4mo - TDP: 7mo - DSS: 11mo

Question 40

A recent study evaluated 36 dogs with AGASACA treated with Palladia +/- surgery, non-concurrent chemotherapy, or both. The PFS was ____ and the OST was ___. Clinical benefit was ___% with a PR of ___% and SD in ___%.

Answer 40

- PFS: 10mo - OST: 28mo - CB: 70% - PR: 20% - SD: 50%

Question 41

A recent study evaluated response and outcome following Palladia for stage 4 AGASACA in 15 dogs. No CR or PR was achieved, but a clinical benefit was seen in ___%. PFI was ____ and MST was ____.

Answer 41

- CB: 87% - PFI: 12mo - MST: 12mo

Question 42

A recent prospective trial evaluated tolerability of a novel 3D-CRT RT protocol (20 x 2.5Gy) for 12 dogs with AGASACA. Grade 3 acute side effects were seen in ___%, which resolved within 4 weeks. Late toxicity (chronic colitis) was seen in ___%.

Answer 42

- acute: 100% - late: 17%

Question 43

A very recent study of 35 dogs treated with bilateral anal sacculectomy for unilateral AGASACA found ___% of presumed unilateral AGASACA to be bilateral tumors.

Answer 43

20%

Question 44

A recent retrospective study of 28 dogs with massive AGASACA (>5cm) treated with anal sacculectomy was performed. ___% grade 2 intra-operative complication rate and a ___% post-operative complication rate was reported. ___% developed fecal incontinence, tenesmus, or anal stenosis. LR occurred in ___% and ___% of dogs with LN metastasis at time of surgery developed distant metastasis. PFI was ____ and OST was ____. LN metastasis was a negative prognostic indicator for PFI but not OS.

Answer 44

- 18% - 36% - Fecal incontinence: 0% - LR: 37% - distant met: 41% - PFI 7mo - OST: 22mo