Melanoma

Question 1

A study evaluating the development of a xenogeneic DNA vaccine program for canine malignant melanoma utilized a 3 cohort scheme, evaluating increasing doses of xenogeneic plasmid DNA encoding either human tyrosinase, murine tyrosinase, murine GP75, 50mcg muTyr, 100/400/800 mcg HuGM-CSF, or combination MuTyr/HuGMCSF. What were the MSTs and AEs?

Answer 1

MST
- huTyr: 13mo
- muGP75: 5mo
- muTyr: 8mo
- 50mcg MuTyr: 8mo
- 100/400/800mcg HuGM-CSF: 5mo
- MuTyr/HuGM-CSF: >13mo (not reached)

AEs:
- minimal to mild discomfort at injection site and depigmentation/vitiligo at injection site

Question 2

A recent multi-institutional retrospective study of canine foot pad malignant melanoma in 20 cases treated with surgery +/- adjuvant therapy reported a metastatic lymph node rate at diagnosis of ___%, an overall metastatic rate of ___%, a PFI of _______ and a MST of ______.

Answer 2

• ln met rate at diagnosis: 20%
• overall met rate: 55%
• DFI: 3mo
• MST: 8mo

Question 3

Evaluation of accuracy for 18F-FDG PET/CT for detection of lymph node metastasis in canine oral MM was prospectively performed. CT sensitivity was ____% and specificity was ____%. PET/CT sensitivity was ____% and specificity was ___% when primary tumor site and use of SUV were used. SUV cutoff was _____.

Answer 3

CT:
- Se: 83%
- Sp: 94%

PET/CT:
- Se: 100%
- Sp: 94%

SUV cutoff: 3.3

Question 4

___% of previously diagnosed or suspected OMM in cats were confirmed to truly be OMM with IHC. _____ is required for accurate diagnosis of thought to be OMM in cats.

Answer 4

• 9%
• IHC

Question 5

A histological classification scheme in nonocular melanocytic neoplasia in cats was recently proposed. Name 3 prognostic factors. What classified tumors as “high” grade? What was the sensitivity and specificity of this grading scheme for tumor related death? The MST of “low” grade tumors was ______ and the MST of “high” grade tumors was _____. The MST was not reached for tumors arising from what locations?

Answer 5

• prog factors: tumor site, MC (>/= 4/10hpf), and intratumoral necrosis
• high grade: >/= 4/10hpf and/or presence of intratumoral necrosis
• Se: 80%
• Sp: 92%
• MST not reached for low grade
• MST high grade: 3mo
• MST not reached for tumors arising from skin, digit, 3rd eyelid, conjunctiva

Question 6

The post-surgical outcome and prognostic factors in canine malignant melanoma of the haired skin was recently assessed in 87 cases (Thamm). The PFS was ____, the MST was ______, the metastatic rate was ____%, the local recurrence rate was ___%, ______ and _____ were significantly associated with decreased PFS and OST.

Answer 6

• PFS: 3.5yrs
• MST: 3.7yrs
• Met rate: 22%
• local recurrence: 8%
• increasing MI and age = negative prog

Question 7

Tumor size as a predictor of lymphatic invasion in oral melanoma in dogs was recently assessed. Lymphatic invasion was confidently ruled out when tumors were ______ in size (100% sensitivity) and was confidently ruled in when tumors were _____ in size (100% specificity).

Answer 7

• < 6.5mm
• > /= 2.5cm

Question 8

Prognostic impact of bone invasion in canine oral malignant melanoma treated by surgery and anti-CSPG4 vaccination was recently assessed. MST of dogs with evidence of bone invasion was significantly shorter at ______ compared to those without at _______. Dogs with “soft tissue” tumors has significantly longer MST at ______ compared to those with “hard tissue” tumors at _____.

Answer 8

• MST bone invasion: 13mo
• MST no bone invasion: 35mo
• MST “soft tissue” tumors: 35mo
• MST “hard tissue” tumors: 16mo

Question 9

The most sensitive and specific markers for canine melanocytic neoplasms are ______ and ______. Which one is more sensitive?

Answer 9

Melan-A and PNL-2
PNL-2

Question 10

______ is a good marker to differentiate melanoma from STS with 90% specificity.

Answer 10

SOX-10

Question 11

_______ is an available ICC marker for melanoma in dogs.

Answer 11

Melan-A

Question 12

For cutaneous/digit malignant melanoma in dogs, tumor thickness _____ is associated with a favorable prognosis while tumor thickness ______ is associated with a poor prognosis.

Answer 12

</= 0.95cm: favorable

> 0.95cm: poor

Question 13

______ is the most useful parameter for prognostication in canine melanocytic neoplasms.

Answer 13

Ki67

Question 14

A prospective clinical trial evaluating masitinib for the treatment of advanced canine malignant melanoma found a MST of ____ with _______ effectiveness.

Answer 14

MST 4mo
mild effectiveness –> don’t use

Question 15

_______ is a targeted therapy that inhibits NAE and has shown potential in canine melanoma cells through induction of DNA re-replication and senescence.

Answer 15

pevonedistat

Question 16

A recent large retrospective analysis of 131 dogs with oral melanoma (adequate local control, microscopic dz and gross disease included) treated with Oncept vaccine +/- surgery or RT reported a TTP of _____, PFS of _____, and tumor-specific OS of _____.

Answer 16

• TTP: 10mo
• PFS: 9mo
• Tumor specific OS: 17mo

Question 17

A retrospective study of 101 dogs with oral melanoma treated with weekly or biweekly 6Gy x 6 RT protocol in the microscopic or gross disease setting reported a PFS of ____ and and OS of ____. Dose intensity did NOT impact survival.

Answer 17

• PFS: 6mo
• OS: 8mo

Question 18

Difference in outcome between curative intent vs. marginal excision as treatment in dogs with oral MM and the impact of adjuvant CSPG4-DNA vaccination was assessed in 155 cases. Overall DFI was significantly shorter in dogs treated with marginal excision at ______ compared to curative intent at _____ but differences in MST was not significantly affected with marginal excision reported to be _____ and curative-intent reported to be _____. When the subpopulation of vaccinated dogs were assessed, both marginal excision DFI (_____) and MST (____) were both significantly shorter compared to curative intent DFI (_____) and MST (_____).

Answer 18

Overall DFI
- marginal: 6mo
- curative: 8mo

Overall MST
- marginal: 15mo
- curative: 20mo

Vaccinated DFI
- marginal: 6mo
- curative: 11mo

Vaccinated MST
- marginal: 16mo
- curative: 44mo

Question 19

What 5 breeds are predisposed to oral melanoma?

Answer 19

Scotties, Goldens, Chows, poodles, dachshunds

Question 20

***The location of canine oral MM in decreasing frequency is:

Answer 20

gingiva > lips > tongue > hard palate

Question 21

***Name the IHC diagnostic cocktail that is especially helpful in amelanotic melanoma and the sensitivity and specificity.

Answer 21

Melan-A, PNL-2, TRP-1, TRP-2

Se: 94%
Sp: 100%

Question 22

*** Dogs with digital melanoma without metastasis treated with digit amputation have a reported MST of ____ with a 1-year survival rate of ___% and 2-year survival rate of __%. Metastasis is found in ___-___% of dogs at presentation.

Answer 22

• MST 12mo
• 1 year survival: ~50%
• 2-year survival: 11-13%
• 30-40%

Question 23

**What are the reported MST ranges for dogs with oral malignant melanoma treated with surgery based on tumor stage? More recent reports suggest dogs with stage I oral melanoma treated with standardized therapies, including surgery, RT, and/or chemotherapy have a MST ranging from ____-____. Other studies have found a PFS of ____.

Answer 23

Stage I
- MST: 17mo - 29mo
- MST: recent standardized: 12-14mo
- PFS (other studies): 19mo

Stage II
- MST: 5mo-27mo

Stage III
- MST: 6mo - 7mo

Stage IV
- MST 2-3mo

Question 24

*** For dogs with oral MM, LN metastasis is present in ___% with lymphadenopathy and ___% with normal sized lymph nodes.

Answer 24

• Lymphadenopathy: 70%
• Normal LNs: 40%

Question 25

Dogs with oral MM with incomplete histologic excision are ____ times more likely to die of tumor-related causes compared with dogs with complete histologic excision.

Answer 25

3.6 times

Question 26

Dogs with oral MM with tumors caudal to third premolar tooth are ____ times more likely to die of tumor-related causes.

Answer 26

4.3 times

Question 27

***Dogs with oral MM treated with RT have reported partial responses ranging from ___-____, complete responses ranging from ____-____, and overall responses ranging from ___-____.

Answer 27

- PR: 25-67% - CR: 19-69% - overall RR: 82-94%

Question 28

A recent study reported a 0% complete and partial response rate to RT for dogs with oral MM and a ___% ORR when including SD.

Answer 28

73%

Question 29

For dogs with oral MM treated with RT in the gross disease setting, reported PFS ranges from ____-____.

Answer 29

PFS: 4-9mo

Question 30

Local recurrence rates of ____% and ___% have been reported for dogs with oral MM after treatment with RT for microscopic disease while local progression is reported in ___% of dogs when treated in the macroscopic setting.

Answer 30

- Local recurrence (microscopic): 26% and 27% - Local progression (macroscopic): 45%

Question 31

MSTs for dogs with oral MM treated with RT range from ____-____ using various protocols.

Answer 31

MST: 5mo - 15mo

Question 32

***Five cats with oral MM treated with RT have a reported MST of _____.

Answer 32

MST 5mo

Question 33

A study of 39 dogs with incompletely excised oral MM treated with cisplatin (10-30 mg/m2) or carboplatin (90mg/m2) concurrently with RT (6 x 6Gy) reported a local recurrence of ___%, median time to metastasis of ____ and MST of _____.

Answer 33

- local recurrence 15% - median time to met: 10mo - MST 12mo

Question 34

A multicenter retrospective study of 17 dogs with oral melanoma treated with surgery and carboplatin (300mg/m2), including 11 dogs also treated with RT, reported an overall PFS of ____ and MST of ____. No significant outcome when RT was added to treatment protocol BUT the proportion of dogs with local recurrence was lower in RT group at ___% compared to dogs not treated with RT at ___%.

Answer 34

- PFS: 9mo - MST: 15mo - local recurrence RT group: 27% - local recurrence no RT: 67%

Question 35

***A prospective study of 27 dogs with malignant melanoma of oral and non-oral sites treated with RT only or RT and Temodar (5 x 6Gy) was performed. Both groups had similar overall response rates with the RT group being ___% and the RT + Temodar group being ___%. TTP was significantly longer for the RT + Temodar group at ____ compared to RT only group at ____. MST was NOT statistically significant between the two groups with the RT + Temodar group being ____ and the RT alone group being ___.

Answer 35

Overall RR: - Temodar + RT: 81% - RT alone: 87% TTP - Temodar + RT: 7mo - RT alone: 4mo MST - Temodar + RT: 13mo - RT alone: 6mo

Question 36

*** A study of 105 dogs with oral tumors included 38 with MM treated with 4Gy on MWF for a total dose of 48Gy. The overall PFS was ____. Size was significant prognostic factor where PFS for T1 tumors was ____, T2 tumors was ____, and T3 tumors was ____. The most common cause of failure in this study was _______.

Answer 36

- overall PFS: 8mo - PFS T1: 11mo - PFS T2: 6mo - PFS T3: 7 mo - failure: distant metastasis

Question 37

A study of dogs with oral melanoma treated with 9Gy x 4 weekly fractions assessed tumors size on tumor outcome. Dogs with tumors ____ cm^3 were more likely to achieve CR and have significantly better MST than dogs with larger tumors. What were the MSTs based on tumor size?

Answer 37

<5cm^3 MST <5cm^3: 22mo >5cm^3: 4-5mo

Question 38

***A study of dogs with oral MM treated with a variety of radiation protocols and adjuvant therapies reported MST of _____ for stage I, _____ for stage II, _____ for stage III, and ____ for stage IV.

Answer 38

MST - Stage I: 25mo - Stage II: 9mo - Stage III: 5mo - Stage IV: 3mo

Question 39

The highest reported response rates for dogs with measurable oral MM treated with chemotherapy is carboplatin at ___%.

Answer 39

28%

Question 40

***A multi-institutional safety and efficacy trial compared 58 prospectively enrolled dogs with surgically resected stage II and III oral melanomas treated with adjuvant Oncept vaccine to historical controls. Dogs treated with Oncept had significantly better outcome with MST _____ vs. historical group at _____. Only ___% of dogs died as a result of their disease in the vaccinated group.

Answer 40

MST - Oncept: not reached - control: 11mo - 26%

Question 41

A prospective study of dogs with stage II and III oral melanoma were treated with surgery alone vs. surgery and adjuvant CSPG4 vaccination. Outcomes were significantly better in the vaccinated group. For vaccinated dogs, the DFI was ____, the MST was ____, 1-year survival rate was ___%, and 2-year survival rate was ___%. For non-vaccinated dogs, the DFI was ______, the MST was _____, the 1-year survival rate was ___% and 2-year survival rate was ___%.

Answer 41

Vaccinated group: - DFI: 16mo - MST: 23mo - 1 year survival: 74% - 2 year survival: 30% Non-vaccinated group: - DFI: 6mo - MST: 7mo - 1 year survival: 26% - 2 year survival: 5%

Question 42

Treatment of dogs with digital melanoma with digit amputation and adjuvant Oncept resulted in significantly improved outcomes compared with historical controls with digit amputation alone. For dogs vaccinated with no metastasis at presentation, MST was ____ and the 3-year survival rate was ___%. Clinical staging was also prognostic. The MSTs for stage I tumors was _____, stage II was _____, stage III was _____, and stage IV was _____.

Answer 42

- MST (no mets): 18mo - 3 year survival (no mets): 48% MST - stage I: > 33mo - stage II: > 36mo - stage III: 11mo - stage IV: 3mo

Question 43

What are the MI cutoff values for prognosis in canine oral/lip and digit/cutaneous MM?

Answer 43

oral/lip <4/10hpf = favorable prognosis >/= 4/10hpf = poor prognosis cutaneous/digit <3/10hpf = favorable prognosis >/= 3/10hpf = poor prognosis

Question 44

What are the nuclear atypia value cutoffs for prognosis in canine oral/lip and digit/cutaneous MM?

Answer 44

oral/lip <30% = favorable prognosis >/= 30% = poor prognosis digit/cutaneous <20% = favorable prognosis >/= 20% = poor prognosis

Question 45

What degree of pigmentation is associated with a favorable prognosis in canine oral/lip and digit/cutaneous MM?

Answer 45

oral/lip >/= 50% = favorable prognosis digit/cutaneous scale of 2 = favorable prognosis lower values have uncertain prognosis

Question 46

Which prognostic factor is negatively associated with outcome in canine cutaneous/digit MM but not oral/lip MM?

Answer 46

presence of ulceration only negative for digit/cutaneous

Question 47

What level of infiltration/invasion is associated with prognosis in canine oral/lip and cutaneous/digit MM?

Answer 47

oral/lip - shallow with no bone invasion = favorable prognosis - deep with possible bone invasion = poor prognosis cutaneous/digit - limited to dermis = favorable prognosis - extends beyond dermis = poor prognosis

Question 48

What are the Ki67 index cutoffs for canine oral/lip and digit/cutaneous MM?

Answer 48

oral/lip <19.5 = favorable prognosis >/= 19.5 = poor prognosis digit/cutaneous <15 = favorable prognosis >/= 15 = poor prognosis

Question 49

***A retrospective study of 151 dogs with excised oral melanoma +/- adjuvant therapy was performed. For dogs with normal sized lymph nodes, cytology revealed metastasis in ___% and histology was ___%. For enlarged lymph nodes, cytology revealed metastasis in ___% and histology was ____%. The overall MST was ____. Tumor recurrence occurred in ___%. Poor prognostic factors on multivariate analysis were tumor size, patient age, and intralesional excision. The MSTs for patients with tumors <2cm was ___, 2-4cm was ____, and > 4cm was ____. Patients older than ____ had a worse outcome of ____ compared to patients younger than ____ with a MST of ____. Patients who had intralesional excision had a MST of ____, marginal excision was ____, and wide or radical excision was _____. A clear survival benefit was NOT evident with any systemic adjuvant therapy, including Oncept. The MST for patients with adjuvant therapy was ____ and no adjuvant therapy was _____.

Answer 49

Regional LN mets: - Normal node size, cytologic metastasis = 16% - Normal node size, histologic metastasis = 44% - Enlarged node, cytologic metastasis = 44% - Enlarged node, histologic metastasis = 84% - oMST: 12mo - Tumor recurrence: 16% - Tumor size: < 2 cm MST = 21mo 2-4 cm MST = 8mo > 4cm MST = 6mo - Patient age > 12 years MST = 8mo < 12 years MST = 21mo Excision - Intralesional MST = 4mo - Marginal MST = 12mo - Wide or radical MST = 12mo Adjuvant therapy - Yes: MST = 12mo - No: MST = 11mo

Question 50

***An older retrospective study evaluated the prognostic significance of stage in dogs with oral malignant melanoma. Negative prognostic factors included stage, tumor size, histologic criteria, and evidence of metastasis. What were the MSTs according to stage in this study of dogs treated with surgery?

Answer 50

MST - Stage I: 17-18mo - Stage II: 5-6mo - Stage III: 3mo

Question 51

***What breeds are associated with a more benign or aggressive biologic behavior in canine oral or cutaneous MM?

Answer 51

- benign: Doberman and miniature schnauzer - aggressive: miniature poodle

Question 52

***What is the MST for canine oral MM without treatment?

Answer 52

MST 2mo

Question 53

**What is MST for canine lingual MM