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BCOP > melanoma > Flashcards

melanoma Flashcards

1
Q

epidemiology

A

5th common men, 6th common women. 10x more in whites than AA. 50% higher in white men than women. Worldwide incidence varies 100 fold. Death rates declining in white 50yo.

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2
Q

etiology

A
  1. UV radiation not proven but consistently strong association
  2. genetic (small % of overall) red hair, freckling
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3
Q

pathogenesis

A
  1. majority of melanocytes at epidermal-dermal junction and choroid of the eye
  2. progression involves series of steps
  3. secretes a variety of growth autocrine and paracrine factors-> proliferation
  4. tumor associated antigens
  5. oncogenes (ie. BRAF mutation)
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4
Q

risk factors

A
  1. lattitude, intesity of solar exposure
  2. whites fair hair (red and blond), light colored eyes (blue and green)
  3. blistering sunburns (especially during youth)
  4. intermittent, intense exposure worse than chronic, occupational
  5. previous non-melanoma skin CA, parent, increased atypical nevi >3, increased common nevi >101
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5
Q

pathophysiology

A

classified by histologice subtype (these do not determine tx)

  1. superficial spreading (>70%) - flat, irreg, spreading
  2. nodular (15-30%) pure vertical, aggressive, dark blue-black
  3. lentigo maligna - less propensity to metx
  4. acral lentiginous - more common in blacks, asians, hispanics, plantar surfaces
  5. uveal -most common intraocular
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6
Q

prevention

A 
#minimize UV radiation
#avoid sun 10am to 4pm
#SPF 15 or higher, wide brim hats
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7
Q

screening

A 
#predicated on relationship of tumor thickness / spread - CATCH EARLY - surgery highly successful if lesion  yearly exam
#suspicious lesions should be excised/biopsied by a professional (no shave bx)
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8
Q

signs and sx

A

usually asx

itch, ulceration, bleed

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9
Q

disease at presentation

A

local 84%, regional 8%, mets 4%, unstaged 4%

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10
Q

natural history

A

radial growth -> vertical growth -> lymph node spread -> mets (any organ in body, unlike non-melanoma)

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11
Q

Diagnosis

A 
#Bx - plan as to not interfere with LN mapping and sentinel node bx
#H&P -assess risk factors, FH, total body skin exam
#stage III: CXR, LDH, CT (however, these are relatively insensitive at detecting distant mets)
#stage IV: BRAF mutation testing
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12
Q

staging

A 
#correlates size =T of lesion and N with likelihood of mets
#ulceration, bleeding -> worse prognosis
#Breslow TNM classification has replaced Clark
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13
Q

prognosis

A 
#5yr OS = 98% local, 62% regional, 15% distant
#larger than 4mm thick have 50% chance of relapse
#older pt >70 and african am= worse prognosis
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14
Q

treatment principles

A 
#according to stage of dz
#surgery key
#XRT limited to palliative setting
#adjuvant chemo not recommended outside of clinical trial
#immunotherapy
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15
Q

treatment -adjuvant immunotherapy - interferon alpha 2b (1yr, best duration unk) AND pegylated interferon alpha 2b (up to 5yr)

A 
#primary lesions > 4mm (stage II) or involving regional LN rendered disease free by surgery (stage III)
#low or intermediate NOT effective
#OS risk reduction 11%
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16
Q

interferon alpha 2b AND pegylated interferon alpha 2b ADR

A

acute constituitional sx ( fever, chills, malaise, arthralgias), fatigue, HA, wt loss, myelosuppression, depression, hypothyroidism

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17
Q

management of interferon ADR’s - anorexia

A

calorie counts -> if miss 3meals /7 days HOLD for 1 week -> RED 33-50% with nutrition consult

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18
Q

management of interferon ADR’s - wt loss

A

> 10% wt loss -> HOLD 1 wk, RED 33-50% with nutrition consult

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19
Q

management of interferon ADR’s - fatigue

A

thyroid test-> if > or = to 2 pt decline in ECOG-> HOLD 1-2 wks, RED 33-50%

20
Q

management of interferon ADR’s - depression

A

Beck’s inventory, moderate depression, HOLD 1-2 wks, RED 33-50% with psych eval

21
Q

management of interferon ADR’s - AST

A

LFTs, when >10x ULN HOLD until <3x ULN, RED 33-50%

22
Q

management of interferon ADR’s - WBC

A

ANC, 250, RED 33-50%

23
Q

example inteferon alpha 2b dose

A

20MU/m2/d IV 5days/wk x4wk, THEN 10MU 3days/wk x48wk

24
Q

example peg-interferon dose

A

6ug/kg/wk x8wks, THEN 2ug/kg/wk up to 5 yrs

25
Q

treatment -adjuvant immunotherapy - node (-) pts 1-4mm thick or <1mm with ulceration

A

no std adjuvant recommended

26
Q

treatment - metastatic - preferred regimens

A

ipilimumab (asx or more indolent), vemurafenib (sx, rapidly growing, quicker higher response rate), clinical trial, high dose IL-2

27
Q

treatment - metastatic - other active (not preferred) regimens

A

dacarbazine, temozolomide, biochemotherapy, paclitaxel, imatinib (c-Kit mutation), paclitaxel/carboplatin

28
Q

treatment - metastatic - aldesleukin (IL-2)

A 
#RR 15-25%, CR 2-5% (some durable)
#DO NOT use with untreated / active brain mets
#tx related mortality 2.2%, need adherence to pt-eligibility criteria, well trained staff
29
Q

treatment - metastatic - aldesleukin (IL-2) - ADR

A

cytokine induced capillary leak sx (hypotension, visceral edema, dyspnea, tachycardia, arrhythmia), visceral edema(= pulm congestion, pleural eff, edema), constitutional sx, pruitis, eosinophilia, BM suppression, inc LFTs, renal failure, N/V

30
Q

treatment - metastatic - interferon

A

RR 15%, rare CR, unlike IL-2 CR not durable, not widely used

31
Q

treatment - metastatic - combo interferon +IL-2

A

RR 18%, few CRs

32
Q

treatment - metastatic - combo interferon +IL-2 +histamine

A 
#phase III subset with hepatic mets appeared to respond
#phase III trial though showed NO benefit over dacarbazine
33
Q

ipilimumab MOA

A

blocks CTLA-4 (CTLA-4 turns off t cells)

34
Q

ipilimumab - 1st line tx

A

compared ipi + dacarbazine vs dacarb
OS 11.2 vs 9.1mo
dose at 10mg/kg instead of 3 - cost is issue
no good monotherapy data

35
Q

ipilimumab - 2nd line tx

A

OS 10.1 vs 6.4mo
some durable responses, 24mo OS 24%
3mg/kg q3wk x4oses (FDA and NCCN approved for primary and secondary)

36
Q

ipilimumab response determination (1 of 4 categories)

A

different because based on activating the immune system to kill melanoma cells; because of this pts should receive ALL 4 doses unless severe or life threatening tox
A: response in baseline lesion
B: SD with slow, steady decline in total tumor volume
C: response after initial increase in total tumor volume
D: reduction in total tumor volume after the appearance of new lesions

37
Q

Differences between WHO vs irRC criteria for response:

A

new, measurable lesions: always represent PD vs incorporated into tumor burden
new, nonmeasurable lesions (<5x5mm): PD vs do not define progression but preclude CR
non-index lesions: define response vs contribute to defining response

38
Q

ipilimumab ADR

A

most common skin and GI track (think GVHD), treat with steroids until median resolution time of 2 weeks, mild may use topical; colitis grade 2-budesonide, grade 3 or 4 high dose steroid, if no response after one wk use infliximab

39
Q

dacarbazine in metastatic dz

A 
#only FDA approved chemo for metastatic melanoma
#RR 20-25%, CR uncommon, lasts 5-7mo
40
Q

temozolomide in metastatic dz

A

beneficial for pt with CNS mets

41
Q

nitrosureas, cisplatin, and taxanes in metastatic dz

A

RR 10-20%, RR <10%, RR 6-18% respectively

42
Q

combination chemo in metastatic dz

A

combo only increases toxicity, does NOT improve OS

43
Q

biochemotherapy in metastatic dz

A

increases RR, but dose NOT improve OS

44
Q

vemurafenib

A

BRAF v600e mutant, 81%RR
1st line: 6mo OS 84% vs 64% (dacarbazine)
2nd line: CR 6%, PR 47%

45
Q

vemurafenib ADR

A

most common: rash, photosensitivity, hair loss, joint pain

grade III tox: cutaneous squamous cell CA (12%, remove surgically, continue tx), rash, GI, fatigue, joint pain

BCOP (32 decks)

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