Melanoma

Question 1

Who gets melanoma?

Answer 1

Common is dogs with skin pigmentation, rare in cats

Question 2

What are the 9 common location for melanoma?

Answer 2

Haired skin, oral cavity, nailbed, footpad, eye, GI tract, nasal cavity, anal sac, or mucocutaneous junction.

Question 3

5 common sites of metastasis for melanoma?

Answer 3

LNs, lungs, liver, meninges, and adrenal glands

Question 4

Etiology of melanoma in dogs? In humans?

Answer 4

Etiology in dogs in not established. In humans, cutaneous melanomas arises from exposure to UV light.

Question 5

Melanoma is the most common oral malignancy, T/F?

Answer 5

True

Question 6

5 dog breeds commonly affected by melanoma?

Answer 6

Scottish terriers, golden retrievers, Chow Chows, poodles, and daschunds

Question 7

Found in the following 4 locations in the mouth by order of decreasing frequency?

Answer 7

gingiva, lips, tongue, hard palate

Question 8

Feline melanoma is rare but malignant in most cases, T/F?

Answer 8

True

Question 9

Melanoma can masquerade like what tumor?

4 IHC markers useful for diagnosing melanoma?

Answer 9

STS

PNL2 and tyrosinase in addition to Melan A and S-100.

Question 10

BRAF mutation is common in OMM, T/F?

Answer 10

False

BRAF, member of MAPK signaling pathway that is commonly mutated in human cutaneous melanoma but not in oral human melanomas.

Question 11

Transcriptome analysis has uncovered new therapeutic targets in canine melanomas

Answer 11

The melanoma-associated genes clustered in the areas of focal adhesion and PI3k-Akt signaling pathways, extracellular matrix-receptor interactions, and protein digestion and absorption.

Small subset have exon 11 c-kit gene mutation, therefore use of KIT small molecule inhibitors (particularly in dogs with advanced stage of disease and/or lack of response to Oncept) should be considered.

Somatic mutations in NRAS and PTEN can be found in canine MM and may represent therapeutic targets in future.

Question 12

Biologic behaivour of melanoma is based on what 4 factors?

Answer 12

Biologic behavior is variable and based on anatomic site, size, stage, and histologic parameters

Question 13

Behaivour of haired skin melanomas?

Treatment?

Additional diagnostic to help predict malignancy potential in cutaneous melanoma?

Answer 13

Haired skin melanomas that are not in proximity to mucosal margins behave in benign manner.

Surgical excision is curative but interpret margins and cytologic features.

Ki67 IHC has been reported to reliably predict potential malignant behavior for cutaneous melanoma.

Question 14

Dogs with digit melanoma without LN or distant metastasis treated with digit amputation have MST of?

Metastasis at time of presentation is seen in?

Prognosis for dogs with melanoma of the foot pad has been reported, however Bergman has found this anatomic site to be similar in metastatic potential and prognosis to digit melanoma

Answer 14

12 months with 1- and 2- year survival rates of 42% to 57% and 11% and 13%

30% to 40% of dogs.

Majority of dogs will develop regional or distant metastatic disease

Question 15

What is prognostic in oral melanoma in dogs and what is the WHO staging system?

Stage I

Stage II

Stage III

Stage IV

Answer 15

Tumor size

WHO staging scheme is based on local tumor size, regional and distant metastasis

Stage I (<2 cm diameter): nonmetastatic tumor

Stage II (2-4 cm): nonmetastatic tumor

Stage III (>4 cm and local LN metastasis)

Stage IV (distant metastasis)

Question 16

MST for dogs with oral melanoma treated with surgery are:

Stage I

Stage II

Stage III

Answer 16

Stage I: 511 to 874 days (1.4 years - 2.4years)

Stage II: 160 to 818 days (5 - 27 months)

Stage III: 168 to 207 days (5.6 - 6.9 months)

Question 17

Recent study suggests dogs with stage I oral melanoma treated with standardized therapies including surgery, RT and/or chemotherapy have MST of?

Most dogs die from?

Answer 17

12 to 14 months with most dogs dying from distant metastasis and not local recurrence.

Question 18

LN should not be sampled if lymphadenomagaly is not present, T/F?

LN metastasis can be present in __ of dogs with lymphadenomagaly and ___ in normal sized LNs?

Answer 18

False - should always be sampled

70%, 40%

Question 19

Most effective treatment option for melanoma?

Answer 19

Wide surgical resection with 2-3 cm margins

Question 20

Melanoma is ____ tumor requiring a _____ dose in each fraction for local control.

Answer 20

Radioresistant, higher

Relative radiosensitivity of melanoma in animals has not been determined and nor has ideal dose per fraction in hypofractionated protocols.

Question 21

Partial response and complete response to RT are ____ and ____ with overall response rate of ____.

PFS ranges?

Answer 21

25% to 67%

19% to 69%

82% and 94%

PFS ranges from 3.6 to 8.6 months.

Question 22

MST for dogs treated with RT?

Answer 22

MST for dogs treated with RT range from 4.5 to 14.7 months

Question 23

Study with 39 dogs with incompletely excised oral melanoma treated with either cisplatin or carboplatin once weekly approximately 1 hr before receiving RT (6 weekly x 6 Gy)

Local recurrence reported in ____ median time to metastasis was ___ months, MST was ____ months.

Answer 23

15% dogs,

10.2 months

MST 11.9 months

Question 24

Prospective study with 27 dogs with malignant melanoma of oral and nonoral sites, 15 dogs treated with RT (5 fractions of 6 Gy over 2.5 weeks) alone and 12 dogs with RT and temozolomide (60 mg/m2 PO for 5 consecutive days).

Overall response rates for both groups was?

Median time to progression was longer in dogs treated with RT and temozolomide was ___ vs. ___ for RT alone

MST was not significantly different (RT alone 192 days and 402 days for RT and temozolomide).

Answer 24

86.7% and 81.1%

205 days versus 110 days for RT alone

Question 25

Size of irradiated oral melanoma is prognostic in several studies.

Study with 105 dogs with oral tumors, 38 were MM treated with 4Gy M, W, F (total dose 48 Gy), median PFS was 7.9 months. T1 lesions (PFS 11.3 months), T2 and T3 (PFS 6.0 and 6.7 months).

Another study with oral melanoma treated with 9 Gy per fraction once weekly for 4 weeks, tumor < 5cm3 more likely to achieve complete response and had better MST. MST was 86 weeks (5 cm3), 16 weeks (5 to 15 cm3), and 21 weeks (> 15 cm3).

Tumor size also affects times to first event, pulmonary metastasis, and death. In one study dogs treated with different RT protocols, dogs with Stage 1 had MST 758 days, stage II 278 days, stage III 163 days and stage IV 80 days.

Question 26

Several studies found dogs with oral melanoma have higher plasma VEGF concentration than normal control dogs. The effect of VEGF levels had on patient outcome was investigated in 39 dogs, 6 had melanoma.

VEGF levels did not increase over the course of RT, however dogs with higher plasma VEGF levels treated with hypofractionated protocol had a shorter time to treatment failure.

Question 27

Highest reported RR __% for dogs treated with ____ and ___ and ___% for dogs treated with ____.

Answer 27

18%, cisplatin + piroxicam

28%, carboplatin

Question 28

Xenogeneic tyrosinase-DNA vaccine in canine MM. Antibody and T cell responses in dogs vaccinated biweekly for a total of 4 treatments with huTyr demonstrated antigen specific IFN-G T cells with 2 to 5 fold increase in circulating antibodies to huTyr.

Question 29

Xenogeneic DNA vaccination in canine MM?

Answer 29

Safe

Leads to development of anti-tyrosinase antibodies and T cells

Potentially therapeutic

Attractive candidate as an adjuvant

Question 30

Multi-institutional safety and efficacy trial compared 58 prospectively enrolled dogs with surgically resected stage II and III oral melanoma treated with Oncept to a historical control group of 53 dogs.

MST for dogs in historical group was 324 and MST was not reached for vaccinated group because only 26% dogs died as result of melanoma.

Question 31

CSPG4 (Chondroitin sulfate proteoglycan 4) vaccination. Prospective study of dogs with stage II and III oral MM, 19 dogs were treated with surgical resection only and 23 dogs were treated with surgical resection and CSPG4 vaccination. Median disease free interval was 477 days, MST was 684 days and 1- and 2- year survival rates of 73.9% and 30.4% compared with 180 days, 200 days, and 26.3% and 5.3% in the nonvaccinated group.

Question 32

Treatment of dogs with digit melanoma with digit amputation and adjuvant Oncept resulted in significant improved outcomes compared with historical controls with digit amputation alone.

Dogs with metastatic disease had significantly worse MST (105 days) than dogs without metastatic disease at presentation (533 days) with 3- year survival rate of 48% in latter group.

Clinical staging scheme was prognostic with Stage 1 having MST of 952 days (2.6 yr), Stage II 1093 days (3 yr), Stage III 321 days (10 mo), and Stage IV 76 days (2.5 mo).