Exam 2: Melanoma

Question 1

Melanoma

Answer 1

results from the malignant transformation of skin melanocytes or from the transformation of preexisting nevocellular nevi

Question 2

Factors identified in the progression of melanoma

Answer 2

• BRAF
• MEK
• PI3K/AKT
• c-KIT
• Cytotoxic T lymphocytes
• PD-1

Question 3

Superficial spreading melanoma

Answer 3

• 70% of cases
• appears flat but subsequently becomes irregular and asymmetrical

Question 4

Nodular Melanoma

Answer 4

• strictly vertical growth
• raised and asymmetrical
• head, neck, trunk
• more common in men

Question 5

Lentigo Maligna Melanoma

Answer 5

• presents on the face of elderly patients
• tan lesion with areas of brown and black
• has low propensity to metastasize

Question 6

Arcral lentiginous melanoma

Answer 6

• frequently presents on the palms, soles, or under nail beds

Question 7

Uveal melanoma

Answer 7

• occular melanoma
• often metastasis in liver

Question 8

A: ABCDE

Answer 8

asymmetric

Question 9

B: ABCDE

Answer 9

have irregular boarders

Question 10

C: ABCDE

Answer 10

wide variety of colors

Question 11

D: ABCDE

Answer 11

Diameter of > 6 mm

Question 12

E: ABCDE

Answer 12

Evolution of a mole may be indicative of neoplastic transformation

Question 13

Diagnostic Work up

Answer 13

• history and pE
• biopsy of suspected lesion

Question 14

What should happen if melanoma is a clinical or pathologic stage IV?

Answer 14

the tumor tissue should be tested for BRAF V600E and K mutations

Question 15

Surgery

Answer 15

• surgery beyond localized disease is thought to be palliative

Question 16

Radiation

Answer 16

• could be offered in the adjuvant setting for select patients with positive lymph nodes and high risk relapse

Question 17

adjuvant therapy

Answer 17

• traditionally not warranted in the past, but newer data has changed that recommendation
• recommendations are based on stage

Question 18

Stage IB or IIA lymph node negative treatment overview

Answer 18

clinical trial or observation

Question 19

Stage IIB or IIC lymph node negative treatment overview

Answer 19

clinical trial, observation, pembrolizumab

Question 20

Stage III treatment overview

Answer 20

• nivolumab
• pembrolizumab
• dabrafenib/trametinib (if BRAF mutat)
  ±
  radiation or observation

Question 21

Adjuvant Nivolumab

Answer 21

• toxicities were higher in ipilimumab compared to nivolumab
• is now NCCN category 1 recommendation in adjuvant setting

Question 22

Adjuvant Pembrolizumab

Answer 22

• pembro improved recurrence free survival and reduced risk of distant metastases

Question 23

Adjuvant Dabrafenib/Trametinib

Answer 23

• completely resected, stage III disease with BRAF V600E or V600K mutations AND SLN metastases > 1 mm

Question 24

First line treatment options for metastatic melanoma eligible for anti-PD1 monotherapy

Answer 24

• nivolumab
• pembrolizumab
• nivolumab + relatlimab-rmbw

Question 25

First line treatment options for metastatic melanoma with BRAF V600 mutation

Answer 25

- dabrafenib/trametinib - vemurafenib/cobimetinib - encorafenib/binimetinib

Question 26

Certain circumstances metastatic treatment options

Answer 26

- nivolumab/ipilimumab - associated with more toxicities

Question 27

In general, immunotherapy and targeted therapy are preferred for treatment of what?

Answer 27

unresectable or distance metastases

Question 28

when can chemo be considered?

Answer 28

- patients not eligible for any of the recommended immunotherpay options due to progression on prior therapy, unacceptable toxicity, or comorbidities

Question 29

What should be started initially for quicker onset of action?

Answer 29

- targeted therapy - immunotherapy can take weeks to see effect

Question 30

all patients with metastatic disease should be tested for what?

Answer 30

BRAF mutations

Question 31

Vermurafenib

Answer 31

- BRAF V600E - development of squamous cell carcinoma

Question 32

Cobimetinib

Answer 32

in treatment of unresectable or metastatic melanoma in patients with BRAF V600E or V600K mutations - in combo with vemurafenib

Question 33

Dabrafenib

Answer 33

- used in BRAF V600E or BRAF V600K - single agent or with trametinib - squamous cell carcinoma

Question 34

Trametinib

Answer 34

- reversibly and selectively inhibits MEK 1 and 2 activation and kinase actiivty

Question 35

Inhibition of MEK 1 and 2

Answer 35

leads to decreased cellular proliferation, cell cycle arrest, and increased apoptosis

Question 36

Pembrolizumab

Answer 36

- pembro has less toxicities than ipilimumab and PFS and OS were statistically longer

Question 37

Combo Nivolumab/Ipilimumab Treatment

Answer 37

- untreated, unresectable stage III or IV

Question 38

Ipilimumab

Answer 38

- CTLA-4 inhibitor to promote antitumor immunity - some patients will have tumor growth prior to immune system activation

Question 39

Immune related response criteria

Answer 39

- response after initial increase in disease - reduction in total tumor burden after presence of new lesions - very important to understand so therapy isnt stopped based on what was thought to be progesssing disease

Question 40

Immunotherapy toxicities

Answer 40

- rash, pruritis - liver toxicities - diarrhea, colities - neuropathy - pneumonitis - musculoskeletal pain - diabetes - hypophysitis

Question 41

Colitis treatment

Answer 41

- steroids

Question 42

Diabetes treatment

Answer 42

- insulin in all patients

Question 43

Hypophysitis treatment

Answer 43

- hydrocortisone

Question 44

Chemo in the metastatic setting

Answer 44

- rarely cures any patient

Question 45

Melanoma Screening

Answer 45

full body self exam

Question 46

Melanoma Prevetion

Answer 46

- sun protection - SPF > 15