Melanoma Flashcards
management of brain mets in melanoma
IF resectable isolated LARGE brain metastasis → metastasectomy (surgery)
Multiple brain metastasis
IF resectable → surgery or radiosurgery
IF not resectable → whole brain radiation therapy
cutaneous vs. non cutaneous melanoma
cutaneous = typical melanoma noncutaneous = extremely rare. melanoma that develops in other areas of the body where melanocytes are present. Ocular melanoma. Mucosal melanoma.
stage at which melanoma is typically diagnosed
Most cases of malignant melanoma are diagnosed at an early stage, when surgical excision can be curative.
Treatment options for melanoma
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
ipilimumab mechanism
anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] antibody
Role for chemo in metastatic melanoma?
None. Previously used but never demonstrated an OS benefit.
Prevalence of V600 mutation in the BRAF gene in melanoma
High – 50%
BRAF mutation is involved in what pathway
MAPK
Tolerability of BRAF and MEK inhibitor therapy
well tolerated
Management of oligometastatic disease
surgical metastasectomy
Critical prognostic lab in melanoma
LDH
what is talimogene?
attenuated oncolytic herpes simplex virus that contains the granulocyte macrophage colony stimulating factor gene
Options for Management of metastatic melanoma
- Iplimumab + nivolumab (ipi-novo)
- nivolumab single agent
- pembrolizumab single agent
BRAF inhibitors
Encorafenib
Vemurafenib
Dabrafenib
Definition of microscopic satelites
- 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
Melanoma staging based on
1) Thickness
2) presence of ulceration
3) nodal mets, distant mets
Prevalance of BRAF mutation
High – 50%
Targeted therapies for melanoma target…
- BRAF
- NRAS
- MEK
- KIT
N1 in melanoma means
one lymph node
N2 in melanoma means
2 or more nodes
“In transient” or “satelite” metastasis means
- deposit of melanoma that is distinct from primary tumor and is in transient or going toward nodal basin
N2 means
4 or more nodes
Management of involved sentinel node (microscopic)
- no longer do completion specific lymph node dissection
Efficacy of adjuvant radiation in melanoma
- improves local control of bulky disease but not OS
Role for adjuvant radiation
- high risk disease (will improve local control but won’t have any effect on long term survival)
BRAF inhibitors
Vemurafenib
Dabrafenib
MEK inhibitor
Trametinib
General consensus on MEK inhibition
- not typically used as monotherapy, toxic
Caveat about using BRAF inhibitors
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
Combination vs. single agent targeted therapies
- always combination
Prognostic importance of elevated LDH
very poor prognosticator
KIT targeted therapy
Imatinib
Pembro SE’s
- hypothyroidism/hyperthyroidism
- pneumonitis
- colitis
- hepatitis
- skin rashes
Ipi SE’s
- colitis
- hepatitis
- hypophisitis
Combined or single agent CPI in melanoma?
Combined – Ipi + nivo, then can use single agent as maintenance therapy
Importance of PD-L1 expression
- heterogenous and prone to sampling bias so not mandated and shouldn’t get treatment decisions
trade name for talimogene
TVEC
distant mets relatively common in melanoma
brain mets
Responses to targeted therapies for brain mets in general
- good response rates but not as good as with outside of the brain
when to use ipi-nivo for metastatic melanoma
IF large burden of symptomatic disease, elevated LDH (very toxic regimen) –> ipi-nivo
IF asymptomatic –> single agent PD1
Can melanoma lack pigment?
Yes, all changing lesions, regardless of color should be biopsied
Mutations that account for the majority of mutations found in cutaneous melanoma
- BRAF
- NRAS
- NF1
Most common AE of dabrafenib = trametinib
fever/pyrexia (typically occurs early in treatment with incidence decreasing over time)
Most commonly identified somatic mutation in uveal melanoma
GNAQ
Biology of uveal melanoma
- completely distinct from cutaneous
- No BRAF mutation
First line management of metastatic uveal melanoma
- Tebentafusp
- *Doesn’t respond to checkpoint inhibitors
management of retinal detachment from MEK inhibitors
- IF improvement within 3 weeks of therapy interruption, resume (generally doesn’t cause irreversible loss of vision or serious eye damage)
First line options for stage IV merkel cell carcinoma
Avelumab
Pembro
Most commonly identified mutation in familial forms of melanoma
CDKN2A
Gene mutation more common in mucosal melanoma
KIT
Thickness at which sentinel lymph node biopsy is needed (board question)
0.8 mm
