Melanoma

Evaluation

General

  • tumors of the ectodermal origin arising from melanocytes which can be fouund in skin, eye (choroid and ciliary body), URT, GI, bladder, adn reproductive system.
  • 40,300 new cases and 7300 deaths a year.
  • Most arise de novo but 30% from nevi.
  • Differential is junctional nevi, juvenile melanoma, and pigmented basal cell.
  • Incidence of cancer by race
    • white:black :: 10:1

Pathology

  • Lentigo maligna: 10% of all melanomas and are plaque like.
  • Superficial spreading (60%) and **nodular melanoma **(30%) are horizontal spreaders without raised components.

Staging

Clark’s Histological Staging LN Risk Breslow (mm)
I In situ 0-5% <0.76
II Papillary zone 0-5% <0.76
III Interface of papillary/reticular 15% 0.76-1.5
IV Reticular zone 35% 1.5-4
V Subcutaneous fat 50% >4
T-stage Description
T1 ≤ 1 mm
T2 1-2 mm
T3 2-4 mm
T4 > 4 mm
  • a. without ulceration or b. with ulceration
N1 1 LN
N2 2-3 LN
N3 ≥ 4 LN; matted; or in-transit metastasis or satellites with metastasis in regional nodes.

Work-up

  • H/P
  • Biopsy
  • CXR
  • Labs: CBC, CHEM 20

TREATMENT

  • the standard treatment for localized cutaneous melanoma (stage I and II) is wide local excision.
  • for patient with known LN metastases at presentation (Stage III), wide local excision lus therapeutic LN dissection is the accepted surgical approach.
  • adjuvant or post-operative RT may be given depending on the assessment of the margins and microstaging.

SURGERY

Margins

Depth of Invasion Surgical Margin Needed
in situ melanoma 0.5 cm
≤ 1 cm and ≤ 1 mm thick 1 cm
> 1 cm and 1-4 mm thick 2 cm

Elective Nodal Dissection

  • observation
    • lesion up to 1 mm thick
  • SLN biopsy
    • lesion 1+ mm thick

Solitary metastasis

  • Resection for solitary metastasis to
    • subcutaneous tissue
    • lung
    • nonregional LN
    • brain
  • especially for patient with long disease-free interval after primary treatment

RADIATION

Elective Irradiation of Regional LN in Patients w/o Clinically Evident Nodal Disease

Indications Regional Recurrence Rates after Surgery Alone
Clark level ≥ IV 20% (1.5 - 4 mm) and 30-50% (4+ mm)
Breslow thickness ≥ 1.5 mm 20% (1.5 - 4 mm) and 30-50% (4+ mm)
  • most appropriate for H&N patients who are not candiates for systmic therapy or regional dissection

Adjuvant Irradiation of the Primary Site, Indications

Indications Local Recurrence Rates after Surgery Alone
Demoplastic melanoma 23-48% recurrence rate
Positive margin N/A
Locally recurrent N/A
Breslow ≥ 4 mm and ulceration > 15%
Breslow ≥ 4 mm and satellitosis > 15%

Adjuvant Irradiation of the Regional LN

Indications Regional Recurrence Rates after Surgery Alone
Extracapsular extension 31-63%
≥ 4 LN 22-63%
LN > 3 cm 42%-80%
Cervical LN 33-50%
recurrent nodal disease N/A
No completion dissection after positive SLND 20-50%
  • For most patients nodal dissection results in 80% local control
  • For patients with 1 of 6 clinicopathologic features regional recurrence rate is:
    • Surgery alone: 30% to 50%
    • Surgery and radiation 5% to 20%

Dose

  • RTOG 8305 compared large fraction sizes versus conventional doses and response rates were similar but high complication rate with larger fractions.
    • 8 Gy x 4
    • 2.5 Gy x 20
  • MDACC gave 6Gy twice a week to total dose of 30Gy for high risk patients for nodal disease of at least 50%. 5 year survival of 50% and LC was 88%.
    • need to come off cord and small bowel at 24 Gy.
  • large fraction may have more lymphedema especialy for the inguinal area

Metastatic Disease

  • DTIC, BCNU, cisplatin, and tamoxifen has been used with RR as high as 55%.
  • Currently evaluating temozolomide.
  • Surgical resection for oligometastasis of certain sites

Outcome:

5-OS of pathologically staged patients[1]

Stage 5-year survival
I 90%
II 68%
III 45%
IV 10%
+nodes 30%
-nodes 75%

5-OS of pathologically staged patients[1]

IA IB IIA IIB IIC IIIA IIIB IIIC
Ta: Non-Ulcerated T1a T2a T3a T4a N1a N2b N3
95% 89% 79% 67% N2a N2b
67% 54% 28%
Tb: Ulcerated T1b T2b T3b T4b N1a N1b
91% 77% 63% 45% N2a N2b
N3
52% 24%

Normal Tissue Effects

  • Immediate Reaction
  • Few hours after dose greater than 5 Gy, there is an early erythema similar to sunburn, which is caused by vasodilation, edema, and loss of plasma constituents from capillaries.
  • With standard fractionation
  • 2-3 weeks: erythema followed by dry or moist desquamation
Bibliography
1. Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, Urist M, McMasters KM, Ross MI, Kirkwood JM, Atkins MB, Thompson JA, Coit DG, Byrd D, Desmond R, Zhang Y, Liu PY, Lyman GH, Morabito A. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001 Aug 15;19(16):3622-34.PMID: 11504744
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