Melanoma

Question 1

management of brain mets in melanoma

Answer 1

IF resectable isolated LARGE brain metastasis → metastasectomy (surgery)
Multiple brain metastasis
IF resectable → surgery or radiosurgery
IF not resectable → whole brain radiation therapy

Question 2

cutaneous vs. non cutaneous melanoma

Answer 2

cutaneous = typical melanoma
noncutaneous = extremely rare. melanoma that develops in other areas of the body where melanocytes are present. Ocular melanoma. Mucosal melanoma.

Question 3

stage at which melanoma is typically diagnosed

Answer 3

Most cases of malignant melanoma are diagnosed at an early stage, when surgical excision can be curative.

Question 4

Treatment options for melanoma

Answer 4

1) checkpoint inhibitors (pembrolizumab, nivolumab]
2) anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] antibody [ipilimumab]
3) targeted therapy .
4) RT for local control

Question 5

ipilimumab mechanism

Answer 5

anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] antibody

Question 6

Role for chemo in metastatic melanoma?

Answer 6

None. Previously used but never demonstrated an OS benefit.

Question 7

Prevalence of V600 mutation in the BRAF gene in melanoma

Answer 7

High – 50%

Question 8

BRAF mutation is involved in what pathway

Answer 8

MAPK

Question 9

Tolerability of BRAF and MEK inhibitor therapy

Answer 9

well tolerated

Question 10

Management of oligometastatic disease

Answer 10

surgical metastasectomy

Question 11

Critical prognostic lab in melanoma

Answer 11

LDH

Question 12

what is talimogene?

Answer 12

attenuated oncolytic herpes simplex virus that contains the granulocyte macrophage colony stimulating factor gene

Question 13

Options for Management of metastatic melanoma

Answer 13

• Iplimumab + nivolumab (ipi-novo)
• nivolumab single agent
• pembrolizumab single agent

Question 14

BRAF inhibitors

Answer 14

Encorafenib
Vemurafenib
Dabrafenib

Question 15

Definition of microscopic satelites

Answer 15

• Any discontinuous nest of intralymphatic metastatic cells >0.05 mm in diameter that are clearly separated by normal dermis (not fibrosis or inflammation) from the main invasive component of melanoma by a distance of at least 0.3 mm.
• Basically tumor has spread to small areas of skin

Question 16

Melanoma staging based on

Answer 16

1) Thickness
2) presence of ulceration
3) nodal mets, distant mets

Question 17

Prevalance of BRAF mutation

Answer 17

High – 50%

Question 18

Targeted therapies for melanoma target…

Answer 18

• BRAF
• NRAS
• MEK
• KIT

Question 19

N1 in melanoma means

Answer 19

one lymph node

Question 20

N2 in melanoma means

Answer 20

2 or more nodes

Question 21

“In transient” or “satelite” metastasis means

Answer 21

• deposit of melanoma that is distinct from primary tumor and is in transient or going toward nodal basin

Question 22

N2 means

Answer 22

4 or more nodes

Question 23

Management of involved sentinel node (microscopic)

Answer 23

• no longer do completion specific lymph node dissection

Question 24

Efficacy of adjuvant radiation in melanoma

Answer 24

• improves local control of bulky disease but not OS

Question 25

Role for adjuvant radiation

Answer 25

- high risk disease (will improve local control but won't have any effect on long term survival)

Question 26

BRAF inhibitors

Answer 26

Vemurafenib | Dabrafenib

Question 27

MEK inhibitor

Answer 27

Trametinib

Question 28

General consensus on MEK inhibition

Answer 28

- not typically used as monotherapy, toxic

Question 29

Caveat about using BRAF inhibitors

Answer 29

1) Must always be V600E mutation, not a variant BRAF mutation (this can harm patient through paradoxical activation of pathway) 2) Resistance is a problem so response can abate over time

Question 30

Combination vs. single agent targeted therapies

Answer 30

- always combination

Question 31

Prognostic importance of elevated LDH

Answer 31

very poor prognosticator

Question 32

KIT targeted therapy

Answer 32

Imatinib

Question 33

Pembro SE's

Answer 33

- hypothyroidism/hyperthyroidism - pneumonitis - colitis - hepatitis - skin rashes

Question 34

Ipi SE's

Answer 34

- colitis - hepatitis - hypophisitis

Question 35

Combined or single agent CPI in melanoma?

Answer 35

Combined -- Ipi + nivo, then can use single agent as maintenance therapy

Question 36

Importance of PD-L1 expression

Answer 36

- heterogenous and prone to sampling bias so not mandated and shouldn't get treatment decisions

Question 37

trade name for talimogene

Answer 37

TVEC

Question 38

distant mets relatively common in melanoma

Answer 38

brain mets

Question 39

Responses to targeted therapies for brain mets in general

Answer 39

- good response rates but not as good as with outside of the brain

Question 40

when to use ipi-nivo for metastatic melanoma

Answer 40

IF large burden of symptomatic disease, elevated LDH (very toxic regimen) --> ipi-nivo IF asymptomatic --> single agent PD1

Question 41

Can melanoma lack pigment?

Answer 41

Yes, all changing lesions, regardless of color should be biopsied

Question 42

Mutations that account for the majority of mutations found in cutaneous melanoma

Answer 42

- BRAF - NRAS - NF1

Question 43

Most common AE of dabrafenib = trametinib

Answer 43

fever/pyrexia (typically occurs early in treatment with incidence decreasing over time)

Question 44

Most commonly identified somatic mutation in uveal melanoma

Answer 44

GNAQ

Question 45

Biology of uveal melanoma

Answer 45

- completely distinct from cutaneous - No BRAF mutation

Question 46

First line management of metastatic uveal melanoma

Answer 46

- Tebentafusp - *Doesn't respond to checkpoint inhibitors

Question 47

management of retinal detachment from MEK inhibitors

Answer 47

- IF improvement within 3 weeks of therapy interruption, resume (generally doesn't cause irreversible loss of vision or serious eye damage)

Question 48

First line options for stage IV merkel cell carcinoma

Answer 48

Avelumab Pembro

Question 49

Most commonly identified mutation in familial forms of melanoma

Answer 49

CDKN2A

Question 50

Gene mutation more common in mucosal melanoma

Answer 50

KIT

Question 51

Thickness at which sentinel lymph node biopsy is needed (board question)

Answer 51

0.8 mm