Malignant melanoma Flashcards
What are the three main types of skin cancer?
Malignant melanoma
Non-melanoma skin cancers: basal cell carcinoma (BCC) and squamous cell carcinoma
Who is primarily affected by melanoma?
White skinned people
Incidence is approx. equal in men and women
Where are melanomas commonly found (in terms of location on the body)?
Faces and backs of white men and limbs of white women
What does the acronym ABCD(EF) stand for in terms of identifying melanomas?
A - asymmetry, half of the mole does not match the other half B - border (edges are irregular) C - color, varies throughout D - diameter, generally >6mm E - evolution or elevation F- funny mole
What are the risk factors for skin cancer?
Sun exposure - exposure to intermittent intense sun is more of a risk factor than prolonged exposure to UV radiation
Number of moles - the more moles there are, the more likely that one will become melanomous
Skin type - high risk if fair hair or fair skin
Family history
How is melanoma diagnosed?
Examination using a dermascope
Excisional biopsy
Histopathology
How is melanoma staged?
0 - melanoma in situ
1A - <1mm thick
1B - <1mm thick but skin broken/ulcerated
2A/B/C - larger and no spread to lymph nodes/other organs
3A - spread to up to 3 lymph nodes
3B/C - more lymph nodes/ulceration
4- metastatic
How is stage 1-3 melanoma treated?
Excision of tumor followed by wide local excision of healthy tissue
How is stage 4 melanoma treated?
Chemotherapy and biological therapies
What is the chemotherapy regimen of choice for melanoma?
Dacarbazine
What is Ipilimab? How does it work?
A recombinant human monoclonal antibody that binds to CTLA-4.
Blocks CTLA-4 interaction with its ligands CD80 and CD86
The CTLA-4 molecule serves as an immune checkpoint that downregulates the pathways of T cell activation and prevents autoimmunity –> thus the drug is thought to work through a T-cell mediated antitumor immune response.
What is vemurafenib? Who is this treatment suitable for?
Oral tyrosine kinase inhibitor - BRAF inhibitor.
BRAF is mutated in 60% of melanomas and becomes constitutively active driving cell proliferation.
Only suitable for patients with BRAF V600 mutation,
What is BRAF? What is its relation to melanoma?
tyrosine kinase. BRAF is mutated in 60% of melanomas and becomes constitutively active driving cell proliferation.
BRAF600 mutations - glutamate for guanine point mutation.
What is dabrafenib?
BRAF inhibitor
Why might dabrafenib be preferred over vemurafenib?
Similar efficacy but side effects tend to be tolerable
What is pembrolizumab?
‘immuno-oncology’ therapy. Anti PD-1
PD-1 = programmed death receptor. Is found on T cells, blocks the interaction with its ligands PDL1 and PDL2, this stops inhibition of the immune response.
What biological agent tends to the first line treated for stage 4 melanomas without the BRAF600 mutation?
Pembrolizumab - cheaper and more tolerable side effects.
What is Trametinib?
A reversible high selective allosteric inhibitor of mitogen activated extracellular signal-regulated kinase 1 and 2 (MEK1/MEK2) activation.
In melanoma this pathway is often activated by mutated forms of BRAF which activates MEK. so used in patients with BRAF600 mutation.
What is important monitoring required with trametinib?
Elevations in BP have been reported in association with trametinib as monotherapy and in combination with dabrafenib, in patients with or without pre-existing hypertension.
BP should be monitored at baseline and monitored during treatment with trametinib with control of hypertension by standard therapy as appropriate.
