Melanoma Flashcards
What does ABCD stand for when evaluating cutaneous melanoma?
A = asymmetry B = border irregularities C = colour heterogeneity D = dynamics = evolution in colour, elevation or size
What is the Breslow thickness?
Maximum thickness of melanoma in mm
What are 2 types of melanomas associated with a worse prognosis?
Superficial spreading and modular melanomas
Have a higher rate of BRAF and NRAS mutations (= more aggressive disease)
What are two types of melanomas that can be associated with c-kit mutations?
Acral lentiginous and mucosal melanomas in genital region
When should you do mutation testing in melanoma?
All patients with advanced disease
And high risk resected disease
Initially test for BRAF (50%), if negative test for NRAS (15-25%) and consider c-kit
What staging investigations are recommended for high risk melanoma?
Ultrasound for locoregional lymph nodes and sentinal node biopsy
In very high risk consider CT or PET scan
What determines t-stage of melanoma?
Thickness and ulceration
T1 less than 1mm
T4 greater then 4mm
What determines the M stage of melanoma?
Skin/subcutaneous/nodal metastasis (M1a) Lung mets (M1b) Other site of mets or any site of mets with raised LDH (M1c)
Treatment of localised disease?
Wide local excision with wide margins
SLNB if tumor thickness greater then 1mm or greater then 0.75mm with other high risk features (ie. high mitoitic rate)
If SLNB positive can perform complete lymphadenectomy which gives increased relapse free survival but no affect on overall survival
Treatment of local regional disease?
Surgical removal of involved and surrounding tissue and affected lymph nodes - provides relief of local symptoms and in a small subgroup of patients improved overall survival
Need to assess for distant mets before resection
Options of treatment for advanced melanoma?
Surgical resection - complete resection leads to improved overall survival and provides local control
Immunotherapy - check point inhibitors monoclonal antibodies against CTLA-4 and PD1
Targeted therapies - BRAF/MEK inhibitors for BRAF mutations
Radiation - for palliative symptom control
Cytotoxic chemotherapy - low response rate, no overall survival benefit
What are the 2 most common BRAF mutations?
V600E (most common)
V600K
What is CTLA?
CTLA-4 is an alternative binding site on the t-cell
Normally the t-cell recognises antigen expressed on APC and binds with co-stimulatory binding of CD-28 which leads to activation of t-cell. When CTLA 4 binds instead the T-cell is inhibited
CTLA 4 =’brake on immune response
What is the main risk factor for development of melanoma?
UV light (UVB worse then UVA)
What is a monoclonal antibody against CTLA4?
Ipilimumab
What is PD1 and PD-L 1?
PD1 is a receptor on the t-cell with the PDL-1 (ligand) on the tumour cell.
Binding of PD1 to PDL-1 down regulates the T-cell response
What are examples of monoclonal antibodies against PD1?
Nivolumab
Pembroluzimab
What are some side effects of the immunotherapies?
Immune related adverse effects
- colitis, hypophysitis, hepatitis, dermatitis
Less adrs occurs with PD1 inhibitors (main feared side effect is pneumonitis)
How do you treat immune related adverse effects?
If high grade toxicities stop treatment and give steroids
Can consider other immunosuppressive agents (infliximab, MTX, azathioprine)
What is the immune response criteria for checkpoint inhibitors?
The disease is slow to respond and often an increase/progression in disease is seen before response - wait longer time frames for response
This compares to the rapid quick response seen with BRAF inhibitors
What treatments are used in BRAF-mutated melanomas?
BRAF inhibitor (dabrafenib/vemerafenib) in combination with MEK inhibitor (trametinib)
What pathway do the BRAF and MEK inhibitors work on?
MAPKinase pathway (RAS-RAF-MEK-ERK)
