Melanoma Flashcards
(85 cards)
1
Q
What is the incidence of melanoma in the United States?
A
∼87,000 cases/yr of melanoma in the United States (and rising).
2
Q
What are some risk factors for developing melanoma?
A
UV RT, fair complexion, light hair/eyes, numerous benign nevi or larger atypical nevi (>5 mm, variable pigmentation, asymmetric, indistinct borders),
personal Hx of melanoma (900 times), family Hx of melanoma, and polyvinyl chloride exposure
3
Q
In terms of UV exposure, what is the most important risk factor associated with development of melanoma?
A
Intermittent intense exposure to UVA and UVB, such as Hx of blistering burns in childhood, is the most important risk factor for developing melanoma.
4
Q
What are the sex differences in terms of body distribution of melanoma lesions?
A
Males: lesions predominantly on trunk (e.g., upper back)
Females: lesions predominantly on extremities
5
Q
What % of melanomas derive from melanocytic nevi?
A
∼15% of melanomas derive from melanocytic nevi.
6
Q
What are the 2 common types of noncutaneous melanoma?
A
Uveal melanoma and mucosal melanoma
7
Q
What is the most common site of mucosal melanoma?
A
H&N, then anorectal and vulvovaginal regions
8
Q
What % of melanoma pts have LN involvement at Dx, and how does this differ by T stage?
A
15% of pts have LN involvement at Dx, 5% of T1 pts and 25% of ≥T2 pts.
9
Q
What % of melanoma pts present with DM at Dx?
A
5% of pts present with DM at Dx.
10
Q
What proportion of DM pts present with DM from an unknown melanoma primary?
A
One-third of DM pts or 1%–2% of all pts present with mets from an unknown primary.
11
Q
What are the 5 subtypes of melanoma?
A
Superficial spreading, nodular, lentigo maligna, acral lentiginous, and desmoplastic variant
12
Q
Which of the 5 melanoma subtypes is the most common?
A
Superficial spreading (70%) is the most common subtype → nodular (25%).
13
Q
What are typical features of desmoplastic melanoma?
A
Features of the desmoplastic subtype include older pts (60–70 yo), more infiltrative, higher rate of PNI, amelanotic, higher LF rates, and lower nodal mets/DM rates
14
Q
Which melanoma subtype has the best prognosis?
A
Lentigo maligna melanoma has the best prognosis
15
Q
What subtype commonly presents in dark-skinned populations, and what body locations do it commonly affect?
A
Acral lentiginous, which commonly affects the palms/soles and subungual areas, is the most common melanoma subtype in dark-skinned populations.
16
Q
Which subtype of melanoma is most common and has the worst prognosis?
A
Superficial spreading is the most common subtype. This subtype also has the worst prognosis.
17
Q
What are 3 commonly used immunohistochemical stains for melanoma?
A
S100, HNB-45, and Melan-A stains are commonly used for melanoma
18
Q
A pt presents with a pigmented lesion. What in the Hx can help to determine if this is a suspicious lesion?
A
Changes in Asymmetry, Borders, Color, Diameter (>6 mm), and Enlargement (Mnemonic: ABCDE)
19
Q
Per the latest NCCN guidelines, for what melanoma pts should imaging be performed?
A
Per the NCCN, imaging should be performed for specific signs/Sx or stage ≥III (not recommended for Stages IA–II).
20
Q
What are some common DM sites for melanoma?
A
The skin, SQ tissues, distant LNs, lung, liver, viscera, and brain are common melanoma DM sites.
21
Q
What is the preferred method of tissue Dx for a suspected melanoma?
A
For suspected melanoma, full-thickness or excisional Bx (elliptical/punch) with a 1–3-mm margin is preferred for tissue Dx.
22
Q
Why should wider margins on excisional Dx be avoided?
A
Avoid wide margins to permit accurate subsequent lymphatic mapping.
23
Q
For what locations is full-thickness incisional or punch Bx adequate?
A
Full-thickness incisional and punch Bx are adequate for the palms/soles, digits, face, and ears or for very large lesions.
24
Q
When is a shave Bx sufficient?
A
Shave Bx is sufficient when the index of suspicion for melanoma is low.
25
What is the latest AJCC (8th edition) T staging for melanoma?
```
T1: ≤1 mm thickness
T1a: ≤0.8 mm without ulceration
T1b: ≤0.8 mm with ulceration or 0.8–1 mm with or without ulceration
T2: >1–2 mm thickness
T2a: no ulceration
T2b: ulceration
T3: >2–4 mm thickness
T3a: no ulceration
T3b: ulceration
T4: >4 mm thickness
T4a: no ulceration
T4b: ulceration
```
26
What is considered N1, N2, and N3 in melanoma staging?
N1: 1 + node
N2: 2–3 + nodes
N3: ≥4, or matted, or in-transit mets with mets to regional node(s)
27
For melanoma nodal groups, into what further categories are N1–N3 stages broken into and on what basis (for AJCC 8th edition)?
N1a: 1 occult (SLN Bx) node and no in-transit/satellite, and/or microsatellite mets
N1b: 1 clinical node and no in-transit/satellite, and/or microsatellite mets
N1c: no +LNs with in-transit/satellite, and/or microsatellite mets
N2a: 2–3 occult (SLN Bx) nodes and no in-transit/satellite, and/or microsatellite mets
N2b: 2–3 + nodes, ≥1 clinically detected, and no in-transit/satellite, and/or microsatellite mets
N2c: 1 occult or clinical node with in-transit/satellite, and/or microsatellite mets
N3a: ≥4 occult (SLN Bx) nodes and no in-transit/satellite, and/or microsatellite mets
N3b: ≥4, one of which clinical node or any number of matted nodes and no in-transit/satellite, and/or microsatellite mets
N3c: 2 or more occult/clinical nodes and/or any matted nodes with intransit/satellite, and/or microsatellite mets
28
For AJCC 8th edition, what replaces the micromets vs. macromets distinction for nodal staging?
```
Clinically occult (typically found on SLNB) = “a,” vs. clinically detected (by
exam or imaging) = “b”
```
29
How do M1a, M1b, M1c, and M1d differ in a pt with metastatic melanoma?
M1a: skin, ST, distant LNs
M1b: lung only with or without M1a sites
M1c: non-CNS viscera or other sites with/without M1a or M1b sites
M1d: CNS mets with or without M1a, M1b, M1c sites
30
What does the parenthetical 0 or 1 denote in the most current M-staging (e.g., M1a(0) vs. M1a(1))?
(0) : normal LDH
| (1) : elevated LDH
31
Describe the overall clinical stage groupings per the latest AJCC classification.
```
Stage 0: TisN0
Stage IA: T1aN0
Stage IB: T2aN0 or T1bN0
Stage IIA: T3aN0 or T2bN0
Stage IIB: T4aN0 or T3bN0
Stage IIC: T4bN0
Stage III: any N+
Stage IV: any M1
```
32
Describe the overall pathologic stage groupings per the latest AJCC classification.
```
Stage 0: TisN0
Stage IA: T1a or T1bN0
Stage IB: T2aN0
Stage IIA: T3aN0 or T2bN0
Stage IIB: T4aN0 or T3bN0
Stage IIC: T4bN0
Stage III: any N+ (see AJCC manual for specific breakdown of IIIA–D)
Stage IV: any M1
```
33
What are the Clark levels? Under what circumstance does the Clark level need to be known on the pathology report for a pt with melanoma?
```
Level I: epidermis only
Level II: invasion of papillary dermis
Level III: filling papillary dermis, compressing reticular dermis
Level IV: invading reticular dermis
Level V: SQ tissue
```
The Clark level should be provided on the pathology report for lesions ≤1 mm; not used in latest AJCC staging system.
34
What are the similarities and differences b/t clinical and pathologic staging for melanomatous lesions?
Both require microstaging of the primary after resection:
Clinical staging: clinical exam + radiology allowed (after complete resection)
Pathologic staging: pathology assessment of LN after dissection
35
What should the pathology report reveal about the primary tumor in a pt with a newly diagnosed melanoma after surgical resection?
The pathology report should list the tumor thickness, ulceration status, mitotic rate, deep/peripheral margins, LN/ECE status, evidence of satellitosis, and Clark level (for lesions ≤1 mm).
36
What are some adverse features on pathology after surgical resection for a melanoma?
Adverse pathology features after surgical resection include +margins (+deep margin), LVSI, and a mitotic rate >1/mm2.
37
For clinical staging purposes, what stage designates regional nodal involvement?
Stage III designates nodal involvement in melanoma staging.
38
What is the most powerful prognostic factor for recurrence and survival for pts with melanoma?
Tumor thickness
39
What are 3 favorable clinical factors at presentation for pts with a newly diagnosed melanoma?
Female sex, young age, and extremity location are all favorable prognostic factors
40
What are 5 poor prognostic factors on pathology in melanoma?
Increasing thickness, # of nodes involved, ulceration, Clark level (if <1 mm), and satellitosis are 5 poor prognostic factors in melanoma.
41
What are microsatellites as seen with melanoma?
With melanoma, microsatellites are discrete nest of cells >0.05 mm that are separated from the body of the primary lesion by collagen or fat.
42
What are satellite mets as seen with melanoma?
Gross cutaneous or SQ intralymphatic mets, observed ≤2 cm from primary Dz.
43
What are the in-transit mets seen with melanoma?
Gross cutaneous or SQ intralymphatic mets, observed >2 cm from primary Dz, but before reaching the 1st echelon nodes
44
In order of frequency, which melanoma sites have the highest LR rates after Sg?
Melanoma sites with the highest LR rates after Sg (in descending order of frequency): H&N (9.4%) > distal extremities (5%) > trunk (3%) > proximal extremities (1%) (Balch CM et al., Ann Surg Oncol 2001)
45
What is the approximate 5-yr OS for melanoma by stage (NCI/SEER)?
Stage I–II: 97%
Stage III: 60%
Stage IV: 16%
46
When is WLE alone adequate as Tx of melanoma?
WLE alone is adequate for in situ or Stage IA lesions without adverse features on Bx.
47
When is SLN Bx clearly indicated?
Tumor thickness ≥1 mm.
48
What is the risk of regional node mets in pts with thin (<1 mm) melanomas undergoing SLNB?
5%
49
In which pts with thin melanomas (<1 mm) might you consider SLNB?
Breslow thickness ≥0.75 mm, Clark level ≥IV, and/or ulceration.
50
In pts with a positive SLNB, is immediate completion LND required?
No. A trial randomizing these pts to completion LND vs. observation with serial US showed no difference in melanoma-specific survival. (MSLT-II, Faries MB et al., NEJM 2017)
51
What volume of Dz did most pts on MSLT II have upon SLNB?
Most pts had low-volume (<1 mm) metastatic deposits.
52
In the MSLT-II trial, were there any endpoints that were improved with immediate LND, compared to observation with LND upon regional LN recurrence?
DFS and lower rate of regional LN recurrence.
53
What is the LN recurrence rate for pN+ melanoma pts after LND?
After LND, the LN recurrence rate for pN+ pts is 30% at 10 yrs. (Lee RJ et al., IJROBP 2000: no adj RT; 45% rcvd chemo)
54
What min surgical margins are required by T stage for the optimal surgical management of melanoma?
```
Min surgical margins for optical surgical management:
Tis: 5 mm
T1: 1 cm
T2: 1–2 cm
T3–T4: 2 cm
```
55
Which randomized trials support the surgical margins currently used in the management of melanoma?
Balch et al. (Ann Surg Oncol 2001): 2 cm vs. 4 cm for >T2; no difference in outcome
Thomas et al. (NEJM 2004): 1 cm vs. 3 cm; 3 cm resulted in better LC for >T2 lesions, but no OS benefit
56
When is elective iliac or obturator LND necessary after resection of an LE melanoma?
Elective iliac or obturator LND is necessary if there are clinically positive superficial nodes, ≥3 superficial +LNs, or if pelvic CT shows LAD.
57
When is primary RT ever indicated for Tx of melanoma?
Primary RT is indicated for medically inoperable pts or lentigo maligna of the face (cosmetic outcome better); this is given as 50 Gy/20 fx or 7–9 Gy × 6 biweekly (Farshad A et al., Br J Dermatol 2002), 1.5-cm margin, 100–250 kV photons.
58
When is adj RT indicated for primary resected melanoma?
Per NCCN: deep desmoplastic melanoma with narrow margins, extensive neurotropism, or locally recurrent Dz
59
When should you consider adj RT for Stage III pts?
In select pts with clinically appreciable nodes s/p LND, with ECE and/or:
- Parotid ≥1 node involved
- Neck ≥2 nodes involved and/or ≥3 cm in single node
- Axilla ≥2 nodes involved and/or ≥4 cm in single node
- Inguinal ≥3 nodes involved and/or ≥4 cm in single node
60
What RCT showed that adj RT improves LN field control, based on the above inclusion criteria?
ANZMTG 01.02/TROG 02.01. (Burmeister et al., Lancet Oncol 2013, updated Henderson et al., Lancet Oncol 2015) 217 pts at high risk for further LN relapse randomized to adj RT (48 Gy/20 fx) or observation. LN field relapse was significantly lower in adj RT arm (HR = 0.56; p = 0.041), but no difference in RFS and OS.
61
In the TROG 02.01 study, what was the most common side effect of RT?
Tissue fibrosis, usually minor in severity
62
In the TROG 02.01 study, which pts experienced significant increase in limb edema after adj RT?
There was a significant increase in lower limb volumes/edema in the pts receiving inguinal nodal RT. There was no significant difference in upper limb sites.
63
Which studies suggest that RT can make up for a lack of formal neck dissection in H&N pts?
MDACC data by Ballo et al. (Head Neck 2005): cN+ in neck s/p local excision only with adj RT; 5-yr LC 93%
Ang et al. (IJROBP 1994): high-risk pts ± LND; 5-yr LC 88%
64
What RT hypofractionation scheme has been used in the adj setting for melanoma of the H&N?
Biweekly 6 Gy/fx × 5 (30 Gy) based on the Ang et al. study (MDACC data):
5-yr LRC was 88%, OS was 47%, and there was min acute/late toxicity. (IJROBP 1994)
65
What was the 1st adj systemic therapy that was demonstrated to improve survival for pts with high-risk Stage III Dz?
High-dose Interferon alfa (IFNa), based on ECOG 1684 and Intergroup E1694 studies.
66
Has adj immunotherapy been shown to improve survival for high-risk Stage III pts?
Yes, ipilimumab (Ab against CTLA-4) at 10 mg/kg (higher dose than 3 mg/kg used in metastatic setting) improved OS compared to placebo, in the EORTC 18071 trial (Eggermont et al., NEJM 2016)
67
What main toxicities were observed with ipilimumab in the adj setting?
Considerable toxicity was observed with ipilimumab at 10 mg/kg. Grade 3 or 4 immune-mediated toxicity occurred in 42%, with some deaths. The most
common were dermatologic, GI, endocrine, and hepatic toxicities.
68
Is there a benefit to hypofractionating RT for melanoma in the adj setting?
No. RTOG 8305 showed no difference b/t 8 Gy × 4 fx and 2.5 Gy × 20 fx. (Sause WT et al., IJROBP 1991)
69
What did the University of Florida experience/study (Chang DT et al., IJROBP 2006) demonstrate regarding adj nodal RT in pts with melanoma lesions of the H&N?
The University of Florida study showed excellent 5-yr LC (87%) and no difference b/t hypofractionation (6 Gy × 5 fx) and standard (60 Gy in 30 fx) dosing. The major cause of mortality was DM.
70
What is generally recommended for a pt with nodal recurrence after primary management for melanoma?
Restaging, FNA or LN Bx → LND if no previous dissection → consider adj RT, immunotherapy, or clinical trial.
71
How is salvage RT delivered in melanoma pts with isolated axillary nodal recurrences?
After axillary LND, RT to the axilla alone is sufficient (the SCV region may be omitted), using 6 Gy × 5 fx (30 Gy) per MDACC data. (Beadle BM et al., IJROBP 2009) The 5-yr LC rate was 88%.
72
What systemic agents are currently being used for metastatic melanoma?
Pembrolizumab (category 1), anti–PD-1 monoclonal antibody demonstrates PFS of ∼35%–50% in advanced melanoma. (Robert C et al., Lancet 2014; Robert C et al., NEJM 2015; Ribas A et al., Lancet Oncol 2015; Ribas A et
al., JAMA 2016)
Nivolumab (category 1), anti–PD-1 monoclonal antibody out performs chemo regarding OS and objective response rate in advanced melanoma. (Robert C et al., NEJM 2015; Weber et al., Lancet Oncol 2015)
Ipilimumab, a monoclonal antibody to the immune checkpoint receptor CTLA-4. (Hodi FS et al., NEJM 2010; Robert C et al., NEJM 2011; Margolin K et al., Lancet Oncol 2012)
The combination of ipilimumab and anti–PD-1 ab nivolumab is moreactive than either monotherapy, but is associated with increased toxicity, and was explored in the CheckMate 067 phase III trial (Wolchok JD et al.,
NEJM 2017); 3-yr OS with both drugs was 58% vs. 52% with nivolumab, and 34% with ipilimumab (Grade 3–4 toxicity was 59% vs. 21% and 28% respectively).
Vemurafenib, a specific inhibitor of V600E mutated BRAF (∼50% of all melanomas). (Chapman PB et al., NEJM 2011; Sosman JA et al., NEJM 2012) In the phase III randomized trial (Chapman et al.) that compared vemurafenib to dacarbazine, vemurafenib had a response rate of 48% (vs. 5%) and an improved OS.
73
What intralesional injection agent has shown efficacy in the phase III setting for pts with unresectable, Stage IIIB–IV melanoma?
Talimogene Laherparepvec (T-VEC): modified HSV that induces tumor cell lysis. (Andtbacka, J Clin Oncol 2015) BCG, IL-2, and Rose Bengal have demonstrated efficacy in phase I/II clinical trials.
74
What is the rate of lymphedema when treating different LN regions with hypofractionated RT?
The rates for lymphedema are 39% for the groin, 30% for the axilla, and 11% for H&N sites. (MDACC data: Ballo MT et al., Head Neck 2005)
75
What is the α/β ratio of melanoma?
For melanoma, the estimated α/β ratio is 2.5. (Overgaard J et al., Lancet 1995)
76
When using a hypofractionated regimen (e.g., 6 Gy × 5 [30 Gy]), at what dose should one come off the cord and small bowel?
24 Gy is the dose tolerance of the cord/small bowel when hypofractionating with 6 Gy/fx.
77
Is there potential for increased toxicity when combining RT with BRAF inhibitors?
YES. There have been reports of radio-sensitization and RT recall (in some cases severe) in pts receiving RT in close proximity to vemurafenib and dabrafenib. Therefore holding Tx with a BRAF inhibitor for some period of time before and after receipt of RT is prudent.
78
Has unexpected toxicity been observed when combining RT with immune checkpoint inhibitors?
There are emerging data for the combination of RT and immunotherapy, and no unexpected toxicity has been reported. (Hiniker et al., Int J Radiat Oncol Biol Phys 2016; Luke et al., JCO 2018)
79
What are the NCCN (2018) f/u recommendations for melanoma by stage?
NCCN melanoma f/u recommendations:
1. Annual skin exam for life (all stages)
2. For Stages IA–IIA: H&P q6–12mos for 5 yrs, then annually; routine labs/imaging not recommended
3. For Stages IIB–IV: H&P q3–6mos for 2 yrs, then q3–12mos for 3 yrs, then annually; routine labs for 1st 5 yrs; consider imaging (CXR, PET/CT, annual MRI brain)
80
What are some toxicities expected after RT for skin cancer?
Telangiectasia, skin atrophy, changes in pigmentation, skin necrosis, fibrosis, osteonecrosis, chondritis, xerostomia, and hearing loss (if treating near the
inner ear).
81
If cartilage is in the RT field, what should the dose/fx be kept below?
The dose should be kept at <3 Gy/fx to reduce the risk of cartilage necrosis.
82
What is the incidence of skin necrosis after RT?
Skin necrosis occurs in 3% of pts (in 13% if fx size is >4–6 Gy).
83
To what dose should middle ear/canal lesions be limited? Why?
Limit middle ear/canal lesions to 65–70 Gy b/c of higher rates (>10%) of osteoradionecrosis with doses >70 Gy.
84
What can be done to reduce the toxicities to surrounding normal tissues from skin irradiation in the H&N region when using electrons?
To reduce toxicities to normal tissues, use lead shielding to block the lens, cornea, nasal septum, teeth, and gums. Use dental wax on the side from which the beam enters to absorb backscatter.
85
Per the latest NCCN guidelines, what should be the f/u intervals for pts with non-melanoma skin cancers?
NCCN non-melanoma skin cancer f/u intervals:
1. Complete skin exam for life at least once/yr
2. For local Dz: H&P q3–12 mos for yrs 1–2, q6–12 mos for yrs 3–5, then annually
3. For regional Dz: H&P q1–3 mos for yr 1, q2–4 mos for yr 2, q4–6 mos for yrs 3–5, then q6–12 mos for life
