skin cancer

Question 1

skin cancer risk factors

Answer 1

fair skin
blonde/red hair
blue, green grey eyes
HISTORY OF SUNBURNS
INTENSE INTERMITTENT SUN EXPOSURE
RECREATIONAL SUN EXPOSURE
TANNING BED USE
advanced age
female
immunodeficiency or immunosuppression
presence of atypical, large, or numerous moles
personal history of melanoma or other skin cancers
xeroderma pigmentosum

Question 2

sun safety preventative measures for skin cancer

Answer 2

limit midday (10AM-4PM sun exposure)
higher risk at higher altitudes
sun protection:
-Ultraviolet protective factor (UPF) clothing rating of >30-50
-Hats, sunglasses
-Sunscreen

Question 3

approximately __ of initial melanoma lesions are found by self-skin examinations

Answer 3

50%

Question 4

benign vs dysplastic nevi

Answer 4

Benign nevi: occur in sun-exposed area, 4-6 mm in diameter, raised or flat, uniform in color, round

Dysplastic nevi: >6 mm, flat macules w/ assymmetry, fuzzy or ill-defined shape, vary in color

Question 5

ABCDEs of melanoma

Answer 5

A: asymmetry
B: border
C: color
D: diameter
E: evolving

Question 6

what are the treatment options for BCC?

Answer 6

Surgery
Local therapy: topical 5-fluorouracil, topical imiquimod, radiation, cryotherapy
High risk of recurrence of non-surgical candidate with BCC: hedgehog inhibitors (vismodegib, sonidegib) or cemiplimab

Question 7

treatment options for advanced or metastatic SCC?

Answer 7

cemiplimab, pembrolizumab, cetuximab, carboplatin + paclitaxel

Question 8

topical 5-FU uses

Answer 8

BCC, SCC

Question 9

5-FU MOA

Answer 9

antimetabolite, pyrimidine analog

Question 10

5-FU dosing

Answer 10

5% cream applied BID X 3-6 weeks (BCC) x 9 weeks (SCC)

Question 11

topical 5-FU side effects

Answer 11

scaling, dryness, stinging, photosensitivity, delayed hypersensitivity reactions

Question 12

topical imiquimod use

Answer 12

BCC

Question 13

imiquimod MOA

Answer 13

immune response modifier, toll-like receptor 7 agonist–> activates immune cells

Question 14

imiquimod dosing

Answer 14

5% cream applied once daily, 5 days per week x 6 weeks

Question 15

topical imiquimod side effects

Answer 15

erythema, dryness, itching, burning, photosensitivity, local inflammatory reactions

Question 16

what are hedgehog inhibitors

Answer 16

vismodegib, sonidegib

Question 17

indications for hedgehog inhibitors

Answer 17

locally advanced BCC that cannot be radiated or surgically resected

Question 18

hedgehog inhibitor drug interactions?

Answer 18

vismodegib: none
sonidegib: CYP3A4 inhibitors/inducers

Question 19

hedgehog inhibitor side effects

Answer 19

vismodegib: alopecia, dysgeusia, weight loss, fatigue, nausea

sonidegib: SCr elevation, fatigue, muscle toxicity (spasms, pain, CPK Elevation)

Question 20

checkpoint inhibitors vs targeted therapy in BRAFm?

Answer 20

solid evidence for using checkpoint inhibitors FIRST: more effective than targeted therapy

Question 21

what are the BRAF inhibitors

Answer 21

dabrafenib, vemurafenib, encorafenib

Question 22

what are the MEK inhibitors

Answer 22

trametinib, cobimetinib, binimetinib

Question 23

difference between BRAF and MEK inhibitors

Answer 23

BRAF: selectively inhibit mutated BRAF kinase
MEK: inhibit downstream MEK to delay acquired resistance with BRAF inhibitors

Question 24

BRAF/MEK inhibitor relationship

Answer 24

BRAF+ MEK inhibitors are always given together
for efficacy & prevents side effects

Question 25

what are the targeted therapy combos

Answer 25

Dabrafenib + trametinib
Vemurafenib + cobimetinib
Encorafenib + binimetinib

Question 26

Side effects related specifically to BRAF inhibition

Answer 26

SECONDARY SKIN CANCERS (lower risk when used with MEK inhibitors)
palmar-plantar erythrodysesthesia

Question 27

side effects related to MEK inhibition

Answer 27

serious ocular toxicity, cardiotoxicity (reduced EF), acneiform rash

Question 28

dabrafenib/trametinib side effect

Answer 28

pyrexia

Question 29

vemurafenib/cobimetinib side effects

Answer 29

photosensitivity, QTc prolongation

Question 30

encorafenib/binimetinib side effects

Answer 30

ocular toxicity, QTc prolongation

Question 31

what side effect occurs in 55% of patients treated with BRAF/MEK inhibitors

Answer 31

PYREXIA

2-4 weeks after initiation

Question 32

management of pyrexia with BRAF/MEK inhibitors?

Answer 32

give antipyretics, supportive care, prednisone 10 mg daily

Fever 100.4-104 F: withhold BRAF inhibitor until fever resolves, then resume at same or lower dose

Fever of 104: withhold BRAF inhibitor until febrile reaction resolves for at least 24 hours, then resume at lower dose OR permanently discontinue BRAF inhibitor

Question 33

what are the most common immune-related adverse effects with immune checkpoint inhibitors

Answer 33

rash, pruritis
liver toxicity
diarrhea, colitis
hypophysitis

Question 34

managing grade 1 irAEs (asymptomatic/mild)

Answer 34

continue immune checkpoint inhibitor, provide supportive care, local or topical therapy if appropriate

Question 35

managing grade 2 irAEs (moderate, minimal local or noninvasive intervention indicated)

Answer 35

hold immune checkpoint inhibitor
prednisone 1 mg/kg/day

Question 36

managing grade 3 irAEs (severe or medically significant, hospitalized but not life threatening)

Answer 36

hold immune checkpoint inhibitor and consider permanent discontinuation
prednisone 1-2 mg/kg/day

Question 37

managing grade 4 irAEs (life threatning)

Answer 37

permanently stop immune checkpoint inhibitor
IV methylprednisolone 1-2 mg/kg/day, consider additional immunosuppressants

Question 38

clinical pearls for irAEs

Answer 38

steroids are needed until Grade 1- at least 4-6 weeks

for doses >60 mg, divide dose- not before bed

rec PJP prophylaxis if >20 mg/day x 4 weeks

may need additional insulin if T1DM

Slow taper needed