melanoma

Question 1

What are the referrals based on genetics for melanoma

Answer 1

Families with ≥3 cases of melanoma
x2 cases of melanoma in first degree relatives
First degree relative with melanoma and pancreatic cancer (P10 or P16)

Question 2

What sites of melanoma are there

Answer 2

Skin
CNS & uveal
Aerodigestive - nasopharynx and oral cavity
GU tract

Question 3

What subtypes of melanoma are there

Answer 3

Superficial spreading (commonest)
Nodular
Lentigo maligna, typically on the face
desmoplastic - acral lentiginous are typically on palms, soles, nail beds and mucosal surfaces

Question 4

What stage of melanoma is signified by satellite and in transit mets
And how is each defined

Answer 4

Stage 3 - dermal lymphatic involvement

Satellite lesions < 2cm from primary tumour
In-transit lesions >2cm from primary tumour, but not beyond draining LN

N1c - satellite or in transit mets without regional nodes (n1a-b = one positive node otherwise)
N2c - satellite or in transit mets with 1 regional node
N3 - satellite or in transit mets with ≥2 regional node

Question 5

How to examine a lesion suspicious for melanoma

Answer 5

A - asymmetry
B - border
C - colour
D - Dynamics - changing
E - elevation

Question 6

How is a lesion biopsied

Answer 6

Excision biopsy with 2mm margin, reported for ulceration, depth of invasion and clearance of margins

Question 7

What investigations are done for a potential metastatic melanoma

Answer 7

History and examination
Excision biopsy
Genetic testing if stage IIC or above
SNLB if stage 1b or higher (≥T2a)
Imaging
Bloods - raised LDH is prognostic

Question 8

When is a sentinel LN biopsy done for melanoma

Answer 8

Stage 1b or above (≥T2a)

Question 9

When is genetic testing indicated for metastatic melanoma

Answer 9

Stage IIC or above
(T4b)

Question 10

What imaging is done for a pT1a metastatic melanoma

Answer 10

pT1a (low risk) - no additional ix necessary

pT1b-T4b -> US for locoregional LN metastasis, CT
pT3b or above - brain MRI and PET
Whole body MRI If <24 years old with stage III/IV

Question 11

What imaging is done for a pT1b-4b metastatic melanoma

Answer 11

> pT1b -> US for locoregional LN metastasis, CT

pT3b or above - brain MRI and PET

Whole body MRI If <24 years old with stage III/IV

Question 12

What imaging is done for a metastatic melanoma pT3b or above

Answer 12

pT3b or above - brain MRI and PET
Whole body MRI If <24 years old with stage III/IV

Question 13

When is whole body MRI indicated for metastatic melanoma

Answer 13

<24yrs with stage III-IV

Question 14

How is T1 stage of melanoma split

Answer 14

T1a is size <0.8mm and not ulcerated
T1b is ≤0.8mm and ulcerated, or 0.8-1mm and either ulcerated or not

Question 15

How are the M+ stages of melanoma defined

Answer 15

M1a = skin/subcutaneous mets or distant nodes
M1b = lung mets
M1c = visceral, but not CNS mets
M1d = CNS mets

Question 16

What is the nodal status of stage 1-3 metastatic melanoma

Answer 16

Stages 1 & 2 are node negative
Stage 3 = node positive

Question 17

How is stage 1 melanoma defined

Answer 17

T1-T2a N0

Question 18

How is stage 2 melanoma defined

Answer 18

T2b-T4b N0

Question 19

How is stage 3 melanoma defined

Answer 19

N+ (1-3)

Question 20

How is stage 4 melanoma defined

Answer 20

M+ (a-d)

Question 21

How does the breslow thickness of a melanoma affect the excision margin

Answer 21

Breslow thickness: <1mm
Excision margin: 1cm

Breslow thickness: 1-2mm
Excision margin: 1-2cm

Breslow thickness: 2-4mm
Excision margin: 2-3cm

Breslow thickness: >4mm
Excision margin: 3cm

Question 22

For what stage of melanoma should adjuvant treatment be considered

Answer 22

Stage 2b (T3b-4a) - adj pembro
otherwise stage 3+

Question 23

What is the management of a stage 1a melanoma

Answer 23

stage 1A = T1a-b (<1mm)

WLE only, according to Breslow thickness

Question 24

What is the management of a stage 1b-2c melanoma

Answer 24

Stage 1b (T2a) - stage 2c (T4) - >1-4mm, N0
WLE + SLNB

Completely resected stage 2B (T3b-4a) - adj pembro

Question 25

When is adjuvant pembrolizumab indicated

Answer 25

Completely resected stage ≥2b melanoma (T3b/T4a ie 2-4mm and ulcerated)

Question 26

What is the management of a stage 3 melanoma

Answer 26

Stage 3 = node positive If resectable -> WLE +SLNB +/- nodal clearance (if more than n1a & n2a) Adjuvant treatment (B-raf dependent) B-Raf V600E+ -> adjuvant dab/tram, or nivo or pembro B-Raf V600E- -> adjuvant nivolumab or pembro

Question 27

How is the management of stage 4 melanoma divided

Answer 27

Stage 4 = M+ Resectable disease (primary and mets) Unresectable disease

Question 28

When is adjuvant RT indicated for melanoma What is the recommended dose

Answer 28

Cannot have adjuvant systemic treatment Positive margins not amenable to further surgery / not adequate Sites where local control is critical, such as head and neck 48Gy/20#

Question 29

What is the management of resectable stage 4 melanoma

Answer 29

If metastasis is resectable -> metastatectomy & adjuvant nivolumab (1yr), regardless of B-Raf status, if complete resection

Question 30

How is the management of unresectable stage 4 melanoma divided

Answer 30

By B-Raf V600E status

Question 31

What is the management of B-Raf WT non-resectable stage III/IV metastatic melanoma

Answer 31

Ipi/nivo first line, followed by maintenance nivolumab, independent of PDL1 status, if PS0-1 PS2 - single agent nivolumab or pembrolizumab 2nd line - single agent ipilimumab, if not received previously 3rd line - chemo or BSC

Question 32

What is the management of B-Raf mut non-resectable stage III/IV metastatic melanoma

Answer 32

1st line & PS0-1 Ipi/nivo -> main nivo if possible If quick disease response needed, encorafenib/binetinib or dabrafenib/trametinib, PS2 - pembro or nivolumab single agent 2nd line: Ipilimumab if not received already Single agent pembrolizumab if has received ipi Nivolumb & relatlimab if immunotherapy naive Dab/tram or enco/bini if not used first line

Question 33

When is nivolumab indicated for metastatic melanoma

Answer 33

Adjuvant treatment for completely resected stage 3 or 4 metastatic melanoma Stage 4 unresectable: PS2 1st line

Question 34

When is dabrafenib/trametinib indicated in melanoma

Answer 34

adjuvant treatment of resected stage 3, b-raf v600e positive (assuming Ras WT) or as an option in B-Raf mut non-resectable stage 4 disease

Question 35

What toxicities to dabrafenib and trametinib cause

Answer 35

Dabrafenib - anterior uveitis Trametinib - retinitis, retinal vein occlusion, retinal detachment If retinal vein occlusion, trametinib should be stopped permanently

Question 36

what is given following resection of an isolated melanoma metastasis

Answer 36

adjuvant nivolumab 1yr (stage 4)

Question 37

when can dab/tram be used adjuvantly in melanoma

Answer 37

stage IIIA (node positive disease) following resection if B-raf mutant Stage 2B - use adjuvant pembro regardless of b-raf status