Melanoma Flashcards by Vivian Fan

What cancer is the most common oral malignancy in the dog?

melanoma

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What are the most common locations of oral melanoma?

(in order of decreasing frequency)
Gingiva, lip, tongue, and hard palate

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What are the most common breeds for oral melanoma?

Scottish Terrier, Golden, Chow chow, poodles, and dachshund

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What are some primary factors that determine biological behaviour of oral melanoma?

site, size, location, stage, and histological parameters

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What are some IHC stains for oral melanoma?

Melan-A, PNL-2, S-100, tyrosinase
small subset is also positive for c-kit
NRAS and PTEN mutations also noted

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What’s the MST for digital melanoma without LN or distant metastasis?

MST approx 1 year
1y survival rate 42-57%, 2y survival rate 11-13%

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What’s the % of metastasis on presentation for digital melanom?

30-40%

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What’s the prognosis of foot pad melanoma compared to digital melanoma?

similiar

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Define the oral melanoma staging system.

Stage 1: tumour <2cm, no mets
Stage 2: tumour between 2-4cm, no mets
Stage 3: tumour >4cm and/ or LN mets
Stage 4: any tumour size with distant mets

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What’s the MST for oral melanoma based on staging?

Stage 1: 511-874 days (17-39m) - more recent studies = 12-14m
Stage 2: 160-818 days (5-27m)
Stage 3: 168-207 (5-7m)
Stage 4: 87days (3m)

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What % of LN can be metastatic but still feel normal (ie not enlarged) for oral melanoma?

40%

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What’s the % of LN metastasis for oral melanoma on presentation when the LN is enlarged?

70%

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What are some sites of distant metastasis for melanoma?

abdominal LN
liver
adrenal glands
other intra-abdominal sites

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T or F. Most canine cutaneous melanoma = benign

true

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What’s ideal surgical margin for cutaneous melanoma?

minimum 1-2 cm
ideally 2-3cm and 1 fascial plane deep

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What margin should be aimed for oral melanoma?

1-2cm

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What’s the risk of dying for tumour related causes if the histo margin is incomplete for oral melanoma?

3.6x more likely

At what location oral location is the patient more likely to die due to tumour?

caudal to P3 - 4.3x more likely

How sensitive is melanoma to radiation?

it’s considered radio-resistant

What are the pros and cons of hypofractionated radiation therapy?

Pro:
- less acute side effects
Cons:
- lower overall biological equivalent dose
- higher risk of late side effects

Should you RT a suspect draining LN for oral melanoma even if it’s not enlarged?

Yes, still a 40% chance that it is metastatic

What’s the reported partial response rate for oral melanoma treated with RT?

25-67%

What’s the reported complete response rate for oral melanoma treated with RT?

19-69%

What’s the overall response rate of oral melanoma to RT?

82-94%

How quickly can the oral melanoma respond to RT?

can see dramatic change within a few weeks but durability of control will be an issue PFS 3.6-8.6m

What's the local recurrence rate for microscope oral melanoma treated with RT?

just over 25% (26, 27%)

What's the reported MST for oral melanoma treated with RT?

4.5-14.7m

What's the protocol and MST for the Freeman et al 2003 paper on oral melanoma?

9Gy x 6 weekly fractions most were stage 1 used cisplatin or carboplatin as radiosensitizer - administered 1h prior to RT MST = around 1 year, quite a few were lost to follow-up, estimated survival no mention of side effects median time to metastasis = 10.2m

What are the findings in the Farrelly et al 2004 paper on cat oral melanoma?

hypofractionated RT (3x8Gy) 5 cats, 1 CR, 2 PR MST: 146 days from start of RT. All died due to tumour progression

The longest MST for canine oral melanoma was reported by whom? What was the treatment protocol?

Dank et al, 2012 - 17 dogs total, 11 had Sx + RT + chemo; 6 had Sx + chemo - mostly stage II - PFS = 259 days - MST = 440 days (387days no RT), not significantly changed when RT was added - but those treated with RT had lower local recurrence rate (27% vs 67%)

What were the main findings in the Kawabe et al 2015 paper on oral melanoma RT?

MST Stage I = 758 days (25m) Stage II = 278 days (9m) Stage III = 163 days (5m) Stage IV = 80 days (<3m) Orthovoltage is sig worse than megavoltage

What difference did the Cancedda et al 2016 paper find for canine melanoma?

not just all oral melanoma RT = 5Gy x 5 fraction over 2.5 weeks Adding in temozolomide (60mg/m2 PO x 5 days, 28d cycle) did have a sig improved PFS but not MST RT only: PFS = 110 days, MST = 192 days RT + temozolomide: PFS = 205 days, MST = 401 days - similar ORR 86.7% vs 81.1%

Theon et al 1997. found several prognostic factors for oral tumours treated with RT. What were some for the oral melanomas?

Size RT = 4Gy x 12fx on M-W-F T1- PFS = 11.3m T 2 - PFS = 6.0m T3 - PFS = 6.7m - most common failure = distant metastasis

What was the prognostic factor found in the Blackwood et al 1996 study on RT for oral melanoma?

Tumour <5cm3 more likely to achieve CR and longer MST RT = 9Gy x 4 weekly fx MST = - 21.5m for <5cm3 - 4m for 5-15cm3 - 5m for >15m3

What was the prognostic factor found in the Bateman et al 1994 study on RT for oral melanoma?

Stage (size was found to be non prognostic!) MST - Stage 1 = 758 days (25m) - Stage 2 = 278 days (9m) - Stage 3 = 163 days (4m) - Stage 4 = 80 days (2.6m)

What prognostic factor was found in the Freeman et al 2003 paper?

- no radiographic evidence of bony invsaion = significant longer time to first event - but bone involvement was reported in up to 92% of the dogs with melanoma

In what location would chemotherapy be indicated for canine melanoma?

oral, digital, or pad melanoma any cutaneous with high grade/ high ki-67/ high MI

What's the % of patients responding to chemo in the Boria et al 2004 study?

18%, combination of cisplatin and piroxicam

What's the % of patients responding to chemo in the Rassnick et al 2001 study?

this is canine malignant melanoma (not just oral) 28% with carboplatin

Generally speaking, what's the consensus on chemo following RT in the more recent studies for melanoma?

no significant differences in outcome

How does the Oncept vaccine work?

human tyrosinase DNA, encoded on bacterial plasmid --> dendritic cells present the antigen --> immune response the human tyrosinase is similar enough to canine counterpart that it's recognized as foreign, but will still target the canine ones (overexpressed on tumour cells)

Which tumour type can be difficult to distinguish with oral melanoma?

oral fibrosarcoma