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RACP Oncology 2020 > Melanoma > Flashcards

Melanoma Flashcards

1
Q

What is melanoma?

A

Malignancy of melanocytes

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2
Q

Epidemiology of melanoma

sex, age, survival rate, ethnicity

A

M>F (1.3 to 1)
Median age: late 50s
survival rate: 93% overall, 18% w/ mets
White non hispanics

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3
Q

Risk factors for melanoma

A 
Unprotected sun exposure
sunburn in childhood
fair skin, light eye colour/hair, tendency to burn.
multiple benign/dysplastic naevi
FHx of melanoma
Immunosuppression
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4
Q

Prognosticating factors for melanoma

A
  1. Tumour thickness - 1st predictor
    (higher chance of microscopic involvement of LN)
  2. Mitotic rate (2nd predictor)
  3. Ulceration
  4. Primary tumour location (arm/leg not as bad as scalp, hand, mucosal membrane)
  5. Lymph node involvement
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5
Q

CLassification

A

determined by microscopic evaluation of melanoma skin lesion as well as clinical and radiological assessment.

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6
Q

Genes associated with melanoma

A

BRAF (most common)
MEK

Other mutation in wildtype BRAF:
c-KIT
NRAS
NF1
CTNNB1
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7
Q

BRAF mutation:

  • characteristic
  • position of mutation
  • MOA
A
  • most common mutation (40-60% mutation)
  • less frequent in chronic sun damage
  • common in younger patient
  • 80-90%: mutation in V600E, 20% in V600K
  • causes down stream activation of MEK/ERK pathway causing cell to proliferate
  • useful for direct therapy
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8
Q

Stage 0 melanoma:

  • definition
  • treatment
A

melanoma in situ, located on top layer of skin, not invading dermis.

Tx: resection

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9
Q

Stage 1 melanoma:

  • definition
  • treatment
A

Definition:
<2mm + no ulceration
<1mm + ulceration

Tx:
Surgical resection
+/- sentinel node biopsy if >1mm or if >0.75mm+high risk features

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10
Q

Stage 2 melanoma

A

Definition:
>1mm + ulceration
>2mm + no ulceration

Tx:
Surgical resection
Sentinel node biopsy
Adjuvant RT +/- systemic Tx

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11
Q

Stage 3

A

Definition: LN involvement

Tx:
Surgical resection
Nodal dissection
+ adjuvant therapy and chemotherapy

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12
Q

What is sentinel node biopsy?

A

inject blue dye and radioisotope around primary site.

Sentinel node is then identified by inspection for blue stain and high uptake or radioisotope Node is then removed for analysis.

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13
Q 
Principles of treatment of: 
Stage 4 (metastatic melanoma)
A
  1. Surgery (metastasectomy for a number of lesions)
  2. Immunotherapy
    - IL2
    - immune check point blockade (anti CTLA4, antiPD1, combination of both treatment)
    - experimental: antiPDL1
  3. Targeted therapy:
    - BRAF inhibitor
    - MEK inhibitor
  4. Oncolytic virus
  5. Chemotherapy
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14
Q

BRAF inhibitor:

  • example
  • MOA
  • side effect
  • clinical evidence
A

e.g. vemurafenib + dabrafenib

MOA: stop downstream activation of MEK /ERK thus cease uncontrolled cell proliferation+survival.

Evidence:
Vemurafenib has better outcomes compared to chemotherapy alone.

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15
Q

Combination BRAF/MEK inhibitor:

  • example
  • MOA
  • side effect
  • clinical evidence
  • side effect
A

e.g.
vemurafenib +cobimetinib OR
dabrafenib + trametinib

MOA:
- Resistance to BRAF inhibitors occurs in almost all patient. By inhibiting BRAF+MEK, can prolong PFS and OS.

-decrease side effect from BRAF inhibitors due to a decrease in the paradoxical activation of the MAPK pathway.

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16
Q

Principle of immunotherapy:

- immune response to tumours

A

cancer relies on T cell activation in cancer surveillence.

in cancer, immune tolerance occurs because foreign molecules expressed by tumour cell are viewed as self.

Elimination:
Equilibrium: immune cell can eliminate all cell and prevent mets. This is a static phase
Escape: overtime this can escape, then cause detectable tumour

17
Q

Principle of immunotherapy:

- mechanism of tumour evasion of the immune system

A
  1. Loss of antigenicity (loss of protein on cell surface to create peptide-MHC)
  2. Gain of immunosuppressive properties
  3. Creating an immunosuppresive environment.
18
Q

Effect of immunotoxicity on endocrine

A

Thyroiditis (hypo/hyper)

Hypophysitis:
- visual change, headache, lethargy, imbalance, libido

Adrenalitis

19
Q

Effect of immunotoxicity on endocrine

  • presentation
  • can this be recovered?
  • management
A

Thyroiditis (hypo/hyper)

Hypophysitis:
- visual change, headache, lethargy, imbalance, libido

Adrenalitis:
- lethargy, weight loss, anorexia, nausea/fatigue, hypotension.

Mgmt:

  • regular thyroid and cortisol level.
  • replace hormone
  • endocrine function will not recover with immunosuppression
  • continue immunotherapy
20
Q

Effect of immunotoxicity on respiratory system:

  • presentation
  • management
A

Pneumonitis:

  • imaging changes
  • dry cough
  • dyspnoea
  • tachypnoea

Mgmt:

  • exclude RT changes, infection
  • mild: monitor, r/v frequently
  • moderate: admit, O2 support+ventilation, methylpred
21
Q

Effect of immunotoxicity on liver:

  • presentation
  • management
A

Hepatitis

  • deranged LFT
  • lethargy

Mgmt:

  • mild: observation
  • severe: stop immunotherapy, steroid, mycophenolate
22
Q

Rare presentation of immunotoxicity

A

Neurological:
GBS, encephalitis, MG, Peripheral sensory motor neuropathy.

Blood: haemolytic anaemia, neutropenia, CLL

Renal: nephritis

Cardiac: myositis

Endocrine: pancreatic failure - diabetes

23
Q

What is pseudoprogression in immunotherapy

A

(10% across tumour types) - basically tumour appears to get bigger, patient is systemically well and then after that it shrinks in 4-6 weeks time.

24
Q

Immunotoxicity: cutaneous

- Presentation: common, less common

A

Macular/papular rash over trunk and chest

Less common:
Stephen Johnson syndrome
Sweet syndrome
Bullous pemphigoid

Can worsen psoriasis + lupus

Mgmt:
symptomatic, steroids if bad

RACP Oncology 2020 (4 decks)

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