Radiotherapy Protocol for Malignant Melanoma
Radiotherapy for melanoma is primarily indicated in specific high-risk scenarios rather than as routine treatment, with hypofractionated regimens (30 Gy in 5 fractions over 2.5 weeks) being the most established protocol for adjuvant nodal basin treatment. 1
Primary Disease Radiotherapy Indications
Adjuvant radiotherapy should be considered for:
- Desmoplastic melanoma with narrow margins, locally recurrent disease, or extensive neurotropism 1
- Inadequate resection margins of lentigo maligna melanoma when re-excision is not feasible 1
- R1 resections of melanoma metastases when re-excision is not possible 1
- Head and neck melanomas where re-excision would be cosmetically disfiguring or functionally compromising 1
Routine elective irradiation to regional lymph nodes is NOT recommended 1
Regional Disease: Adjuvant Nodal Basin Radiotherapy
Patient Selection Criteria
Adjuvant nodal basin RT should be considered (Category 2B) in selected patients following resection of clinically appreciable nodes if LDH <1.5 x upper limit of normal AND one or more of the following high-risk features: 1
- Gross nodal extracapsular extension
- ≥4 involved lymph nodes
- Cervical lymph node involvement
- Lymph nodes >3 cm
- Recurrent disease
- Satellitosis 1
Standard Hypofractionated Protocol
The established regimen is 30 Gy in 5 fractions delivered over 2.5 weeks (6.0 Gy per fraction, twice weekly) 1, 2, 3. This protocol achieves:
- 5-year in-field locoregional control of 85-88% 4, 3
- Reduced lymph node field recurrence compared to observation 1
Critical Caveats
Important limitations to understand:
- Adjuvant nodal basin RT reduces locoregional recurrence but has NO impact on relapse-free or overall survival 1
- Benefits must be weighed against increased probability of long-term skin and regional toxicities and potential reduced quality of life 1
- Hypofractionated regimens may increase risk for long-term complications 1
Careful attention to dosimetry is necessary 1, with electron beams of appropriate energies preferred when possible, and junction lines between adjoining fields moved twice to minimize dose heterogeneity 3
Metastatic Disease Radiotherapy
Brain Metastases
Stereotactic radiosurgery and/or whole brain radiation therapy should be used either as adjuvant or primary treatment 1
Extracranial Metastases
Palliative radiotherapy is indicated for:
- Symptomatic brain or localized bone metastases 1
- Other symptomatic or potentially symptomatic soft tissue and/or bone metastases 1
- Unresectable nodal, satellite, or in-transit disease 1
Radiation-Systemic Therapy Interactions
Critical timing considerations when combining with systemic therapy: 1
- Hold BRAF and/or MEK inhibitors 3 days before and after fractionated RT
- Hold BRAF and/or MEK inhibitors 1 day before and after stereotactic radiosurgery or other high-dose-per-fraction regimens
- Interactions between radiation and systemic therapies (BRAF inhibitors, interferon alfa-2b, immune checkpoint inhibitors) need very careful consideration due to potential for increased toxicity, particularly with higher radiation doses 1
Alternative Fractionation
Conventional fractionation (standard daily fractions) is equally efficacious to hypofractionation for locoregional control 4, though hypofractionation is more commonly used given the convenience and established safety profile 2, 3
Toxicity Profile
Acute toxicity with 30 Gy/5 fraction regimen: 2, 3
- Grade 1-2 dermatitis in 80% of patients
- Grade 1-2 mucositis in 85% of patients
- Grade 3 acute adverse events in only 2% of patients
Late toxicity is generally low: 2, 4, 3
- Grade 2 late adverse events in approximately 16% of patients
- Severe late complications (osteoradionecrosis, radiation plexopathy) occur in approximately 4-5% with hypofractionation
- No grade 3 or higher late adverse events in most series
In-Transit Metastases
For non-resectable transit metastases or inoperable primary tumors of the limbs without additional metastases: