melanoma

Question 1

sentinel lymph nodes in melanoma

Answer 1

MSLT1 trial results

Question 2

M1c

Answer 2

non-lung visceral

Question 3

Response rates melanoma

Answer 3

DTIC 10-15; IL2 16, cis 14-29, taxol 14-21

Question 4

CVD

Answer 4

40-44%

Question 5

carbo/taxol melanoma

Answer 5

11,18% RR, no OS benefit to DTIC

Question 6

melanoma RTK RAS path

Answer 6

RTK->RAS-RAF-MEK-ERK-cell prolif

Question 7

dabrafenib/tremetinib CNS

Answer 7

works in CNS

Question 8

vemurafenib v. dabrafenib response

Answer 8

similar efficacy, only a fraction are primarily resistant (10-15%)

Question 9

adverse effects BRAFi

Answer 9

karatinocyte proliferations, hand/foot, SCC, hair thinning, fatigue, fever (more with dabrafenib), prolonged QTc

Question 10

trametinib v. DTIC

Answer 10

improved survival (not as robust as with RAFi), no indication as single agent, more to than RAFi

Question 11

dabrafenib+trametinib

Answer 11

RR increased (76%), increased PFS (9.4 v. 5.8), toxicities are somewhat ameliorated.

Question 12

acral/mucosal melanomas

Answer 12

20% KIT mutation, responds to imatinib

Question 13

UV light and melanoma

Answer 13

UVB is more closely linked.

Question 14

hereditary melanoma

Answer 14

10% of cases. p16/CDKN2A. 30-90% risk of melanoma if carrier of mutation. also pancreatic cancer. BRCA2 as well.

Question 15

mutations in melanoma

Answer 15

BRAF 50-60%, NRAS 25-20%. uveal GNAq/GNA11, acral c-KIT

Question 16

bbbiopsy of suspicious skin lesions

Answer 16

1-2mm margin complete excision is best. If highly suspicoius, shave or curettage contraindicated

Question 17

mucosal melanom

Answer 17

acral lentiginous, c-KIT most comon

Question 18

recurrence with regional ln

Answer 18

if 1+ LN, then 50% reisk of recurrence. Multiple is 75% risk recurrence

Question 19

melanoma staging

Answer 19

stage III: LN+; M1c: elevated LDH or non-lung visceral mets.

Question 20

evaluation of low-risk melanoma

Answer 20

low risk:

Question 21

imaging for local melanoma

Answer 21

indicated for high risk stage II (i.e. >4mm) or LN+ (stage III)

Question 22

sentinal LN biopsy for melanoma

Answer 22

consider for ANY high risk features (i.e. MI>1, ulceration, or >1mm)

Question 23

adjuvant therapy for melanoma

Answer 23

consider for >4mm (IIB- no ulceration, IIC- ulceration) or stage III (+LN)

Question 24

margins of resection needed for melanoma

Answer 24

1cm; 1-2mm–> 1-2cm, 2-4mm–>2cm, >4mm–> at least 2cm

Question 25

interferon regimens for melanoma

Answer 25

IFN-a-2b. 20mil U/m2 5d/wk x 1 month IV, then 10m SQ TID x 11 mo. Another option is pegylated IFN 6ug/kg weekly x 8 weeks, then 3ug/kg weekly x 5 years

Question 26

followup for localized melanoma

Answer 26

no imaging or labs. if >1mm and LN-, get labs, CXR, and LDH. if stage III, get CT or PET

Question 27

vemurafenib toxicities

Answer 27

arthralgia, rash, nausea, photosensitivity, pruritis, hand-foot, keratocancoma. need derm every 2 months, and ECG for QT prolongation risk.

Question 28

dabrafenib dosing

Answer 28

150mg twice daily. causes fever, rash, skin cancer, uveitis, need TTE because of cardiomyopathy in 9%

Question 29

dabrafenib + tremetinib

Answer 29

give 150 BID, with treme 2mg daily. less skin toxicity and SCC, but 70% fever. treat fever with dose interruption or with steroids

Question 30

BRAF V600K mutant melanoma

Answer 30

dabrafenib is approved, not vem.

Question 31

dabrafenib v vemurafenib

Answer 31

more SCC, LFTs, photosense and arthralgia with vem, more fever with dabrafenib.

Question 32

IL-2 for melanoma

Answer 32

2 5d courses of 600-720000u/kg q8hr IL-2, with 7-10 day rest period. max of 5 courses

Question 33

temodar

Answer 33

alkylating agent, at least as effective as DTIC. crosses BBB. 5d regimen is 150-200mg/m2 d1-5 q3-4 wk. extended dosing: 75mg/mg2 x 6 weeks, then 2 weeks off. more OI's lymphopenia.