Melanoma

Question 1

Hypercalcaemia occurs in 10-20% of cancer patients and is associated with a poor prognosis. What are the 2 mechanisms for hyper-Ca of malignancy, and how is this managed?

Answer 1

1. Direct bone destruction (in 20%)
2. Humoral effects caused by PTHrP released by malignant cells (in 80%)

Manage with IVT (normal saline), Frusemide, Bisphosphonates +/- corticosteroids for steroid-responsive tumours

Question 2

What are the 2 main immunotherapies available for melanoma?

Answer 2

1. CTLA-4 monoclonal antibodies
   - Ipilimumab
2. PD-1 monoclonal antibodies
   - Pembrolizumab & Nivolumab

Question 3

40-60% of advanced melanomas have an activating BRAF mutation. What is the most common BRAF mutation?

Answer 3

V600E

- i.e. substitiution of a glutamic acid for valine at amino acid site 600

Question 4

What additional immune therapies are available in BRAF mutation + melanoma?

Answer 4

Dabrafenib (BRAF inhibitor)

Trametinib (MEK1/2 inhibitor)

Question 5

What are the poor prognostic factors for melanoma?

Answer 5

Increased age
M>F
Location (head, neck, trunk, lower extremity)
Sentinel LN +
MAPK mutation +
BRAF mutation + and NRAS mutation + (more likely to present with a higher stage primary tumour)

Question 6

What are the risk factors for melanoma?

Answer 6

• FHx (10% melanomas are familial)
• Repeated or extensive intense exposure to sunlight (especially intermittent exposure & sunburn in adolescence and childhood; UVB > UVA irradiation)
• Tanning beds
• PUVA therapy
• Increased number of naevi
• Familial Atypical Multiple Mole and Melanoma syndrome (FAMMM)
• PHx melanoma
• Immunosuppression