Melanoma

Question 1

OVERVIEW
i) name four concerning symptoms of a mole
ii) what type of melanoma accounts for 5%
iii) what does a/b stage mean? what rate is also commented on microscopically
iv) what is breslow thickness?
v) name four organs it can commonly met to?
vi) what blood marker may be elevated in metastatic disease?

Answer 1

i) change in size, shape, pigmentation, bleeding, itching
ii) mucosal eg ocular, resp, GI, GU, gynae
iii) a/b is presence of ulceration
also comment on mitotic rate
iv) BT is how deep it extends down from the epidermis
v) lung, liver, nodes, brain, bone
vi) LDH - raised = poorer prognosis

Question 2

SURGERY
i) what type of surgery is usually done?
ii) in what two situations is a senteniel node biopsy done?

Answer 2

i) wide local excision
ii) SB if T >1mm or T >0.8mm with ulceration/mitotic index >2

Question 3

BRAF MUTATIONS
i) what % of skin melanomas are they found in? what type of melanoma are they not seen in?
ii) what is the most common mutation? is it inherited?
iii) what other pathway needs to be inhibited alongside BRAF?
iv) what is the only tx available for BRAF WT

Answer 3

i) 45%
not found in mucosal
ii) BRAF V600E - not inherited
iii) also need to inhibit MEK
iv) immunotherapy

Question 4

BRAF MUTATIONS
i) what % of skin melanomas are they found in? what type of melanoma are they not seen in?
ii) what is the most common mutation? is it inherited?
iii) what other pathway needs to be inhibited alongside BRAF?
iv) what is the only tx available for BRAF WT

Answer 4

i) 45%
not found in mucosal
ii) BRAF V600E - not inherited
iii) also need to inhibit MEK
iv) immunotherapy

Question 5

IMMUNOTHERAPY
i) name two molecules that usually switch a T cell off when stimulated? what can be done to help fight the cancer?
ii) what type of drug is ipilimumab?
ii) what types of drugs are nivolumab and pembroliziumab?
iv) how often is ipilim given? what is the response? is there much toxicity

Answer 5

i) CTLA-4 and PD1
block these to allow T cell to be on to fight the tumour
ii) ipi = anti CTLA 4
iii) nivol and pembro - anti PD1
iv) give outpatient infusion every 3 weeks - 10-20% response rate (used to be 0)
>10% grade III or IV toxicity

Question 6

IMMUNOTHERAPY CONTINUED
i) for how long is pembro given? how long is nivol given?
ii) what is the response rate for both? what molecule do they block?
iii) do they have more or less tox than ipilimumab?
iv) what did the checkmate 067 trial show?

Answer 6

i) pembro every 3 weeks for 2 years
nivol every 2 weeks for 1 year
ii) 30-40% response rate > block PD1
iii) less toxicity and more effective
iv) combining nivol and ipi gives best outcomes

Question 7

IMMUNOTHERAPY RELATED TOXICITY
i) what guidelines are used to grade it? what grade is serious and results in stopping tx?
ii) what drugs can be given to mitigate immunotherapy tox? name two drugs
iii) name two drugs that can be given if there is liver tox? what anti IL6R can be given in serious scenarios?
iv) after how many days of tox should HD methyl pred be given?

Answer 7

i) CTC grade
grade III/IV > severe
ii) steroids - can give oral pred or IV methylpred
iii) mycofenilate and tacrolimus
toculizimab if serious tox
iv) 3-5 no improvement

Question 8

OTHER THERAPIES
i) name two checkpoints that can be inhibited to stop tumour progression
ii) how does TIL therapy work?
iii) name four toxic effects of BRAF/MEK inhibition

Answer 8

i) LAG3 and PD1(RELA and NIVOL)
ii) biopsy tumour and isolate out the TIL > stim with IL2 to upregulate and then re infuse back into the patient
iii) fatigue, fevers diarrhoea, thyroid, SCC, pancreatitis, cardiomyopathy