Melanoma- Heemer

Melanoma is greater in what gender? what race?

men>women

white>other races

skin cancer is the ________________ malignancy worldwide.

most common

What are the 2 types of skin cancer?

• nonmelanoma skin cancers

• melanoma

What are some patient-specific risk factors of melanoma?

think: rachel

• adulthood

• sunburns easily

• high degree of freckling/ lots of mole

• blonde/red hair

• blue, green, gray eyes

• race

• family history

What are some external risk factors of melanoma?

• intense, intermittent sun exposure

• sunburn history (>4 painful sunburns before 15)

• exposure to UVA, UVB

• tanning bed use

Family history accounts for 10% of melanoma cases. What are the 2 syndromes associated genetically associated with melanoma?

• Familial atypical multiple mole syndrome (FAMMM)

• dysplastic nevus syndrome

Familial atypical multiple mole syndrome (FAMMM) or dysplastic nevus syndrome are associated with a mutation in the ___________ gene.

CDKN2A

Melanoma arises from ________cytes in the basal layer of the epidermis.

melanocytes

What is the major signaling pathway associated with the development of melanoma?

MAPK

MAPK is responsible for activating what kind of mutations?

• BRAF

• NRAS

• c-KIT

What is the most common BRAF mutation?

V600E (valine substituted for glutamate at position 600) (FYI: another mutation is V600K)

Can melanoma only happen in the skin?

no—> most common in the skin because that’s where the most melanocytes (cutaneous) are, but can occur in other areas of the body (non-cutaneous). ex: gallbladder

What are the 4 histologic subtypes of melanoma?

• superficial spreading melanoma (SSM)

• nodular melanoma

• lentigo maligna melanoma (LMM)

• acral lentiginous melanoma

Which histologic subtype of melanoma has a prolonged growth phase?

lentigo maligna melanoma

Which histologic subtype of melanoma deals with the vertical growth phase and is more aggressive?

nodular melanoma

Which histologic subtype of melanoma is associated with UV exposure? Which isn’t?

• associated—> superficial

• not associated—> acral lentiginous melanoma (ALM)

What are the different clinical subtypes of melanoma?

• nonchronic sun damage (non-CSD)

• chronic sun damage (CSD)

• acral

• mucosal

Answer the following about preventing melanoma?

• avoid what?

• use what?

  • SPF ___ or higher

  • apply ____ minutes before going out

  • reapply every ___ hours

• avoid sun

• use sunscreen

  • SPF 15 or higher

  • apply 30 minutes before going out

  • reapply every 2 hours

What is the general mnemonic for the initial clinical presentation of melanoma?

• “ABCDE”

  • A- asymmetry

  • B- borders

  • C- color

  • D- diameter (>6mm)

  • E- enlargement or evolution

What are the diagonostic tests for melanoma?

• molecular testing for BRAF, NRAS. c-KIT

• sentinel lymph node biopsy

• others: chem, abdomen, pelvic CT, and other scans

Melanoma follows ____ staging.

TNM

How is local and regional melanoma treated?

• local- surgery only

• regional- surgery followed by possible adjuvant therapy

What drugs are the treatment of choice for adjuvant therapy in regional disease melanoma?

• PD-1 inhibitors: Pembrolizumab, Nivolumab

• Dabrafenib, trametinib if BRAF

There are many drugs used in the treatment of metastatic melanoma:

What chemotherapy drugs can be used?

• dacarbazine

• temozolomide (prodrug of dacarbazine)

There are many drugs used in the treatment of metastatic melanoma:

What drug is a recombinant form of IL-2? MOA? What is the main ADR?

• drug: Aldesleukin

• MOA: stimulate immune system

• ADR: capillary leak syndrome

There are many drugs used in the treatment of metastatic melanoma:

Which drug is a CTLA-4 inhibitor?

Ipilimumab

There are many drugs used in the treatment of metastatic melanoma:

Which drugs are PD-1 inhibitors? 1st line for what patients?

• Drugs: Pembrolizumab, Nivolumab

• 1st line for pts. with unresectable/metastatic disease

What is T-VEC therapy? What is its MOA? Where is it administered?

• Talimogene Laherparepvec (T-VEC) is a virus therapy used to kill cancer.

  • virus that is modified is herpes simplex virus type 1

• 2 MOAS:

  • virus replicates within tumor cells and causes death to tumor cells while not killing the normal cells

  • secretes GM-CSF to recruit other immune cells to come and kill the tumor cells

• Admin: injected DIRECTLY into the lesion

There are many drugs used in the treatment of metastatic melanoma:

Which drugs are BRAF Kinase Inhibitors? What mutations do each of these inhibit?

• Vemurafenib- BRAF V600E

• Dabrafenib- BRAF V600E

• Encorefenib- BRAF V600E, V600D, V600K

There are many drugs used in the treatment of metastatic melanoma:

Which drugs are MEK Inhibitors? When are these indicated?

• Trametinib

• Cobimetinib

• Binimetinib

• indicated when unresectable or metastatic melanoma with BRAF V600E or V600K mutations