Melanoma Flashcards
What cancer is the most common oral malignancy in the dog?
melanoma
What are the most common locations of oral melanoma?
(in order of decreasing frequency)
Gingiva, lip, tongue, and hard palate
What are the most common breeds for oral melanoma?
Scottish Terrier, Golden, Chow chow, poodles, and dachshund
What are some primary factors that determine biological behaviour of oral melanoma?
site, size, location, stage, and histological parameters
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
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%
What’s the % of metastasis on presentation for digital melanom?
30-40%
What’s the prognosis of foot pad melanoma compared to digital melanoma?
similiar
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
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)
What % of LN can be metastatic but still feel normal (ie not enlarged) for oral melanoma?
40%
What’s the % of LN metastasis for oral melanoma on presentation when the LN is enlarged?
70%
What are some sites of distant metastasis for melanoma?
- abdominal LN
- liver
- adrenal glands
- other intra-abdominal sites
T or F. Most canine cutaneous melanoma = benign
true
What’s ideal surgical margin for cutaneous melanoma?
minimum 1-2 cm
ideally 2-3cm and 1 fascial plane deep
What margin should be aimed for oral melanoma?
1-2cm
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
How does the use of radiation sensitizer effect the MST of canine oral melanoma? (Freeman et al 2003)
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’s the outcome of feline oral melanoma treated with RT? (Farrelly et al 2004)
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?
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%)
How does tumour stage effect the MST of canine oral melanoma? (Kawabe et al 2015)
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’s the outcome with temozolomide for canine melanoma treated with RT? (Cancedda et al 2016)
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
How does tumour size influence MST? (Blackwood et al 1996)
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 (carboplatin) 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
What are some prognostic factors for canine oral melanoma treated with RT?
- bony invasion (Freeman et al 2003)
- T stage (Theon et al 1997)
- stage (Kawabe et al 2015; Bateman et al 1994)
- tumour size (Blackwood et al 1996)
Which pathway has been persistently found to be activated in canine cutaneous papilloma?
PI3KAkt/mTOR
What’s the utility of pre-op vinblastine/ prednisolone for canine MCT?
What’s the utility of CD20 in the prognosis of canine melanocytic tumours?
high CD20 as significantly associated with tumour-related death, metastasis/recurrence, and shorter overall and disease free survival.
Tumour-infiltrating lymphocytes in canine melanocytic tumours: An investigation on the prognostic role of CD3(+) and CD20(+) lymphocytic populations. Porcellato et al, 2020.
What’s the RR with gilvetmab?
ORR = 41%, mostly stable disease.
total of 5 dogs (20%) had an objective response with 2 dogs having a complete response and 3 dogs having a partial response. A total of 10 dogs (40%) had stable disease and 8 dogs (32%) had progressive disease.
Which IHC are diagnostic for feline malignant melanoma?
PNL-2
Melan-A
What diagnostic criteria has been proposed for “malignant” melanoma in cats?
- if located in lips, oral/nasal mucosa, then needs to have either MI >4/ 10hpf or intratumoral necrosis to be malignant.
- in all other sites, will need both above criteria to be malignant
What’s the MST for cats having malignant melanoma?
MST = 90 days
MST not reached for low grade
How prevalent is SOX10 positivity in melanoma in cats?
SOX-10 nuclear expression was detected in 92% of ocular melanomas, 86% of oral melanomas, and 100% of cutaneous melanomas,
What’s the expression pattern of PD-1 in canine melanoma vs melanocytoma?
significantly higher levels of PDCD1 (PD-1) and CD274 (PD-L1) in melanomas compared to melanocytomas
What’s the prognostic utility of FoxP3 in canine melanocytic tumours?
FoxP3 protein expression greater than 6.9 cells per high-power field was identified as an independent predictor of death.
What’s the outcome of melanocytic tumours of the feline nasal planum?
7/10 cast = malignant, 3 = benign.
Most were euthanized due to tumour progression. MST = 265 days
What’s the significance of tumour infiltrating lymphocytes in feline melanocytic tumours?
May be associated with histologic features of malignancy and loss of melanocytic-specific markers, such as Melan A and PNL2
What’s the prognostic value of tumour infiltrating lymphocytes in canine melanocytic tumours?
high infiltration of CD20(+) TILs was significantly associated with tumour-related death, metastasis/recurrence, and shorter overall and disease-free survival.
What’s the outcome of using masitinib for stage III/IV canine melanoma?
of 17 dogs:
MST = 119 days
2 PR, 7 SD, 8 PD
- masitinib is not an appropriate monotherapy
What’s the COX2 expression status for canine oral and cutaneous melanoma?
- COX-2 was overexpressed in 34% of oral melanomas and 42% of cutaneous melanomas
- associated with various immune cell markers and angiogenesis: CD3 for oral MM; CD3, CD4, FOXP3 and MAC387 for cutaneous MM.
