Skin Cancer: Merkel Cell Carcinoma

Summary:
Wide local excision should always be followed by irradiation. This is an aggressive tumor with high likelihood of locoregional disease at presentation and high rates of recurrence. Adjuvant chemotherapy is controversial and generally not very effective.

Prognosis:
5 year overall survival
Stage I: 80%
Stage II: 60%
Stage III: 40%
Stage IV: 20%
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Etiology:
This is a neuro-endocrine tumor characterized by small-cell cancer cells on pathology. This tumor is generally rare, so high level evidence to guide practice is lacking. Mortality rates are high and double of that expected with melanomas (33 vs 15%).

There is a Merkel Cell Polyomavirus, which suggests a viral etiology. Additionally, immunocompromised individuals seem to be at greater risk.

Approximately 50% present with locoregional disease involving lymph nodes. 30% present with metastatic disease, while only 20% present with localized disease,

Work-up

• Complete history/physical
• CBC, LFTs, RFTs, PT/PTT/INR
• Biopsy
• CT chest
• Anatomical CT for assessment of nodes
  

TNM
T1: < 2 cm
T2: 2 - 5 cm
T3: > 5 cm
T4: Invades bone, muscle, cartilage

N1a:micrometastasis
N1b: macrometastasis
N2: In transit metastasis (between tumor and regional LN or distal to primary)

Staging
Stage IA: T1pN0
Stage IB: T1cN0
Stage IIA: T2-3pN0
Stage IIB: T2-3cN0
Stage IIC: T4N0
Stage IIIA: TxN1a
Stage IIIB: TxN1b; TxN2
Stage IV: TxNxM1

Management:
Wide local excision with 1 - 2 cm margins.
Sentinel lymph node biopsy is bare minimum in all cases. A full lymph node dissection is indicated in the presence of a clinically detectable node (physical exam or CT) or in the presence of a positive SLNBx.

Adjuvant radiation is indicated in all Merkel Cell Cases regardless of margin status or LN status. Doses should be similar to head and neck doses.
Gross disease = 70 Gy
Positive margins or extra-capsular extension = 66 Gy
Negative margins = 60 Gy
Elective nodal irradiation = 50-56 Gy

Volumes:
GTV = gross tumor volume
CTV High Dose = GTV + 1 cm + any LN level with positive LNs
CTV Int Dose = First echelon LN's adjacent to gross disease
CTV Low Dose = Elective nodal irradiation
PTVs = 0.5 - 0.7 cm around CTVs

Chemotherapy:
Regimens are cisplatin and etoposide based as this is a small-cell neuroendocrine tumor. Outcomes and response rates aren't great for these tumors, so it's controversial when chemotherapy is best started.

Skin Cancer: Treatment: BCC and SCC

Summary:
The mainstay of treatment is wide local excision for SCC and BCC with adequate margins. Radiation is an acceptable alternative for non-surgical candidates or tumors in locations where post-operative cosmesis is an issue (primarily ear, nose, lip). Topical treatments are also alternatives, but local control rates are inferior to surgery and radiation.

Indications for post-operative XRT in BCC or SCC are:

• Perineural invasion
  
• Positive margins (not amenable to surgery)
  
• +LNs or +ECE
  
• > T3 (cartilage, bone invasion)
• Recurrent disease

Local Control Rates:

• T1: 95%
• T2: 80%
• T3: 55%
  

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Surgery
Wide local excision and Moh's microsurgery are good options for surgical resection. Adequate margins are required for good local control. BCC requires margins of 4 mm. SCC margins should be 5 mm.

XRT:
Primary radiation is an appropriate alternative to surgery. Local control rates are comparable, but may be slightly inferior (around 98 vs 95%). This is likely because in retrospective studies these were non-resectable tumors or larger tumors compared to surgical series.

A standard dose is 50 Gy in 20 fractions. If the tumor is large or there are concerns for cosmesis you can use 66 Gy in 33 fractions. A less protracted regimen could be 45Gy in 15 or 35 in 5 fractions.

Adjuvant Radiation is indicated in the post-operative setting when there is positive LN involvement or extracapsular extension and perineural invasion. Additionally, in instances where there is bony or muscle invasion or recurrent disease, adjuvant treatment can be added.

Planning Issues:
Primary lesions can be treated with either orthovoltage or electrons. Availability of both allows more treatment options when it comes to difficult locations in the head and neck area. Familiarity with the dosimetry for both is vital for picking the appropriate treatment modality.

Volumes for Electrons:
GTV = gross tumor volume
CTV = 0.5 - 1 cm around GTV
PTV = 0.5 cm
Penumbra = 1 cm

Basically you need a 1 cm penumbra to account for isodose constriction at depth.
Dose is usually prescribe to 90% isodose at depth
When picking an electron energy make sure you cover a few milimetres below the tumor depth.
Don't forget to account for a bolus to bring up the skin dose, particularly for lower MeV electrons.
Don't forget to use wax covered (to minimize back scatter) shield for underlying structures (eyes, lips, mastoid, etc.).

Electron rules of thumb:
Energy/2 = Depth of Rp dose
Energy/3 = Depth of 80% isodose
Energy/4 = Depth of 90% isodose
(Energy/2) + 1 = Thickness for lead shield
(Energy/2) = Thickness for cerrobend shield

Volumes for Orthovoltage:
GTV = gross tumor volume
CTV = 0.5 - 1 cm around GTV
PTV = 0.3 cm
Penumbra = 0.2 cm

Prescribe dose to surface for orthovoltage.
PTV can be smaller because collimation is almost at skin surface.
Penumbra can be smaller because there is no constriction of isodoses at depth.
F-factor is 1 for cartilage, but 4-5 for bone. Dose delivered to bone is higher. F-factor is less of an issure for higher energy orthovoltage beams.
120 kVp will give 100% at surface, and decreases by 10% every 0.5 cm
1 mm shielding is adequate for 120 kVp
240 kVp gives 100% at surface, and decreases by 10% every 1 cm
2 mm shielding is adequate for 240 kVp

Skin Cancer - Staging: Basal cell and Squamous cell carcinomas

The AJCC 7th Edition (2009) has changed the TNM staging to incorporate risk factors. Tumor size has less importance.

T1: < 2 cm
T2: > 2 cm or > 1 risk factor
T3: Invades maxilla, mandible, orbit, temporal bone
T4: Perineural invasion of skull base, axial skeletal invasion

N1: single ipsilateral LN < 3 cm
N2a: Single ipsilateral LN 3 - 6 cm
N2b: Multiple ipsilateral LN < 6 cm
N2c: Multiple bilateral LNs < 6 cm
N3: LN > 6 cm

Stage I: T1N0
Stage II: T2N0
Stage III: T3N0; T1-3xN1
Stage IV: T4N0; TxN2; TxN3; TxNxM1

Risk Factors:

• Invasion: > 2 mm thick, Clark level IV or V; PNI
• Differentiation: Poorly differentiated or undifferentiated
  
• Location: Ear or non-hair bearing lip

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Work-up:
History + Physical exam
Biopsy: excisional or punch
CBC, LFTs, RFTs, PT/PTT/INR
Imaging only if clinical LNs or multiple risks: Regional CT and CXR

Rectal Cancer - Staging

2009 AJCC 7th Edition

T1 - Submucosal invasion

T2 -Suscularis propria

T3 - Serosal invasion, invades peri-rectal fat

T4a - Invades peritoneal viscera

T4b - Invades local structures

N1 - 1-3 lymph nodes

N2a - 4 - 7 lymph nodes

N2b - > 7 LNs

M1a - Metastasis to one site

M1b - Metastasis to more than one site or peritoneum

Stage I - T1-2N0

Stage IIa - T3N0

Stage IIb - T4aN0

Stage IIIa - T1-2N1, T1N2a

Stage IIIb - T3-4aN1, T2-3N2a, T1-2N2b

Stage IIIc - T4aN2a, T3-4aN2b, T4bN1-2

Stage IVa - TxNxM1a

Stage IVb - TxNxM1b

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Investigations:

CT abdo/pelvis

EUS or MRI pelvis

CXR

CBC, LFTs, SMA7, RFTs, CEA

Colonoscopy