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Oncology > Melanoma > Flashcards

Melanoma Flashcards

1
Q

Aetiology of Melanoma

A

UV exposure from UVA and UVB

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2
Q

Risk factors of Melanoma

A 
>10 dysplastic naevi
>100 common aquired naevi
Fair skin
Red hair
High intermittent sun exposure
Age
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3
Q

Prevention of Melanoma

A

Prevent skin exposure

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4
Q

Screening for skin cancer

A

Regular skin examination

Melanomas <0.76mm deep have 10yr survival >95%

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5
Q

Diagnosis of skin cancer

A 
Asymmetry
Border - uneven
Colour - uneven
Diameter >6mm
Enlargement or evolution
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6
Q

Poor prognostic findings

A

Breslow depth

Bleeding and ulceration
Nodular melanoma

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7
Q

Melanoma subtypes

A

Superficial spreading
Lentigo malinga
Acral lentiginous
Nodular

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8
Q

Features of superficial spending melanoma

A

70% of melanomas

Intermittent sun exposure
Mid 40yrs
Trunk and limb location

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9
Q

Features of lentigo maligna melanoma

A

10-15% of melanomas

Cumulative sun exposure
Elderly
Face and neck
Long in-situ phase

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10
Q

Acral Lentiginous melanoma

A

2% of melanomas

Asian and dark skinned people
Palms, soles of feet under nails
Not caused by UV light

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11
Q

Nodular melanoma

A

10-15% of melanomas
50% of melanoma deaths

Vertical growth from outset - rapid growth
Symmetrical, dome shaped, firm amelanotic nodule
Not associated with high mole counts

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12
Q

Immunohistochem diagnosis of Melanoma

A

S100

Melan-A

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13
Q

Melanoma Staging

A 
1 = small primary
2 = Large primary
3 = local disease in lymph nodes
4 = distant mets

Ulceration upstages disease

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14
Q

Poor prognostic factors by stage

A

Stage 1 and 2 = ulceration

Stage 3 = macroscopic disease, >2 lymph nodes, ulceration

Stage 4 = visceral mets except lung and high serum LDH

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15
Q

Staging Melanoma

A

For stage 3 and 4 Melanoma

MRI brain
CT chest, abdomen and pelvis
PET

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16
Q

Treatment of stage 1 disease

A

Local wide excision

17
Q

Treatment of stage 2 disease

A

Local wide excision
Sentinel lymph node biopsy
MRI brain, CT CAP and PET

18
Q

Treatment of stage 3 disease

A

Local wide excision
Total lymph node dissection

Nil other treatment currently recommended
Requires ongoing surveillence imaging

19
Q

Treatment of stage 4 disease

A

Excision of primary
Curative if oligometastatic disease - 1-2 sites only

Common mets sites - skin, lung, brain and bone

Late relapses common

Treatment options:

  • Chemo
  • BRAF
  • BRAF + MEK
  • cKIT
  • CTLA-4 inhibitors
  • PD-1 inhibitors
20
Q

BRAF inhibitors

A

BRAF = signal in the RAS-RAf pathway
Activating mutation of BRAF at V600
–> excessive cell proliferation and survival

50% of melanomas
Related to intermittent sun exposure

Drugs:

  • Vemurafenib
  • -> V600E mutation only
  • -> No CNS activity
  • Dabrafenib
  • -> All V600 mutations
  • -> CNS activity

Side effects:

  • SCCs
  • Arthralgias and fatigue
  • Rash
  • Photosensitivity
21
Q

BRAF + MEK inhibitors

A

MEK is the downstream signal from BRAF in the RAS-AF pathway

Dabrafenib + Trametinib

Improves survival over BRAF alone
Reduces side effects of BRAF inhibition alone

22
Q

cKIT inhibitors

A

KIT = extracellular part of the RAS-RAF pathway

cKIT mutations –> cell proliferation and survival

Acral melanomas

Drug = Imatinib

23
Q

CTLA-4 Inhibition

A

CTLA-4 = a naturally occurring negative regulator of T cell function
Blocks co-stimulatory signalling of CD-28–> inhibits T cell activation and proliferation

Ipilimumab
Monoclonal antibody to CTLA-4 –> blocks CTLA-4 binding –> upregulation of T cell response

Causes psuedo-progression in the first 8 weeks –> regression which is often prolonged

24
Q

Side effects of Ipilimumab

A 
Rash
Colitis
Hepatitis
Neuropathy
Hypopituatarism
Hypo and hyperthyroidism
Adrenal crisis
Pneumonitis

Surrogate for response to treatment

25
Q

Treatment of ipilimumab side effects

A

Anti-inflammatory agents
Prednisone

Severe colitis may require prolonged steroids, TNF inhibition or prolonged bowel rest

26
Q

PD-1 and PD-1 ligand inhibition

A

PD-1 activation –> down regulation of T cell effector functions
PD-1 ligand is selectivity expressed on many tumours

PD-1 blockade –> T cells maintain antitumour activity –> tumour cell death

Pembrolizumab and nivolumab

Same side effects as ipilimumab but at lower rates

27
Q

Combination ipilimumab and nivolumab?

A

Better survival with combination

BUT higher rates of side effects especially higher grade side effects

Oncology (7 decks)

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