Anna Likhacheva, MD
WORKUP
All Cases
H&P (complete skin exam)
Imaging—CT/MRI/PET for specific signs or symptoms or stage ≥III (LN+)
Considerations
ABCDE (asymmetry, borders, color, diameter, and enlargement). Full thickness biopsy rather than shave.
TREATMENT RECOMMENDATIONS BY STAGE
Stage IA–IIC |
Wide local excision (WLE) with minimum 1- to 2-cm margins Sentinel node biopsy (SLNBx) for ulceration or >0.75- to 1-mm thick → Post-op RT to primary site for desmoplastic melanoma, extensive PNI or locally recurrent disease → may consider interferon alpha for stage IIB–IIC |
Stage III |
WLE and SLNBx → Lymph node dissection → Post-op RT to primary site for desmoplastic melanoma, extensive PNI or locally recurrent disease. Post-op RT to a nodal basin for high-risk features* → systemic treatment with Interferon alpha, or high-dose ipilimumab, or biochemotherapy |
Stage IV |
Anti-PD1 therapy, targeted therapy if BRAF mutated, intralesional therapy, biochemotherapy. |
*High-risk features: ECE, ≥1 parotid LN, ≥2 cervical/axillary LN, ≥3 inguinal LN, cervical LN ≥3 cm in size, axillary/groin LN ≥4 cm in size.
TECHNICAL CONSIDERATIONS
Simulation
Set up and technique vary with the site of primary lesion. CT simulation. Use bolus of appropriate thickness to bring dose to surface. Radioopaque wire to outline scars.
Dose Prescription
Clinical practice fraction size varies. Some regimens influenced by radiobiological experiments suggesting that melanoma radiosensitivity is directly proportional to fraction size.
48 Gy in 2.4 Gy/fx was used in the randomized TROG trial. (Max dose to spine and brain is 40 Gy.)
30 Gy in 6 Gy/fx delivered biweekly over 2.5 weeks. (Max dose to spinal cord, brain, bowel, or brachial plexus should not exceed 24 Gy. Diligent dosimetry and set up are essential for this fractionation because dose inhomogeneity is exaggerated. Acceptable coverage of the targeted region when using photons is the 27 Gy isodose line.)
Target Delineation
For adjuvant radiation of the primary site, the target is post-op bed + 2-cm margin for CTV.
For nodal radiation, the target is ipsilateral draining lymphatics.
Cervical region—can use neutral or open-neck position. For latter, use appositional electron fields (bolus is used to limit the dose to the temporal lobe and the larynx).
Axilla—axillary nodes only. No need to target supraclavicular nodes unless involved.
Inguinal—usually less comprehensive than targets for the cervical and axillary regions, to minimize the risk of morbid lymphedema. No need to target external or common iliac nodal chains unless involved.
Treatment Planning
Bolus is necessary to achieve adequate skin surface dose
FOLLOW UP
Annual skin exam for life (all stages)
For stages IA to IIA: H&P q3 to 12 months for 5 years, then annually; routine labs/imaging not recommended
For stages IIB to IV: H&P q3 to 6 months for 2 years, then q3 to 12 months for 3 years, then annually; routine labs for first 5 years; consider imaging.
SELECTED STUDIES
ANZNTG 01.02/TROG 02.01 (Henderson, Lancet Oncol 2015; DOI: 10.1016/S1470-2045(15)00187-4)
Randomized trial of 217 patients: observation versus lymph-node field RT in patients with high risk features. 48 Gy in 20 fx. No difference in overall survival (OS) or RFS at 73 months median f/u. SS improved LRC (HR 0.52.) Increased risk of lower extremity lymphedema in RT group (15% vs. 7.7%.) No difference in lymphedema for upper extremity.
MDACC Experience (Ballo, Cancer 2003)
Retrospective review of 160 patients with cervical LN mets from melanoma. Median dose of 30 Gy at 6 Gy per fraction delivered twice weekly. Adjuvant radiotherapy resulted in a 10-year regional control rate of 94%.
Fractionation for Malignant Melanoma (Chang, Int J Radiat Oncol Biol Phys 2006)
Retrospective study of 56 patients. Post-op RT provides excellent locoregional control and distant metastases is the main cause of mortality. Hypofractionation and conventional fractionation are equally efficacious.
RT for Desmoplastic Melanoma (Guadagnolo, Cancer 2014; DOI: 10.1002/cncr.28415)
Retrospective review of 130 patients with desmoplastic melanoma. LR without post-op RT was 24%, while 7% with post-op RT.
RT for Axillary Metastases (Beadle, Int J Radiat Oncol Biol Phys 2009; DOI: 10.1016/j.ijrobp.2008.06.1910)
Retrospective analysis of 200 patients with axillary metastases. 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the axilla and supraclavicular fossa (EF). RT to the axilla only produced equivalent LR control to EF and resulted in lower treatment-related complications.
RTOG 83-05 (Sause, Int J Radiat Oncol Biol Phys 1991)
Randomized trial of 126 patients: 32 Gy in 4 weekly fx versus 50 Gy in 20 daily fx. No difference between the arms.