Radiotherapy for Melanoma: More than DNA Damage

Area of Science:

• Oncology
• Immunology
• Radiation Oncology

Background:

• Melanoma is often considered radioresistant, but radiotherapy shows promise.
• Melanoma is highly immunogenic, making it a candidate for immunotherapy and radiation-induced immune stimulation.

Purpose of the Study:

• To summarize current clinical practice and evidence for radiotherapy in melanoma treatment.
• To explore the role of radiotherapy as an immune stimulant, particularly in combination with other therapies.

Main Methods:

• Review of clinical practice and existing evidence for radiotherapy in melanoma.
• Discussion of radiobiological mechanisms, including immunogenic cell death and modulation.
• Exploration of combination therapies: radiotherapy with hyperthermia and immune checkpoint inhibitors.

Main Results:

• Radiotherapy can induce an immune response by promoting dendritic cell maturation, upregulating adhesion molecules, and increasing tumor-associated antigens.
• Clinical hyperthermia enhances the immune response to radiotherapy in melanoma patients.
• Higher fraction sizes in stereotactic radiotherapy are more immunogenic than conventional fractionation.
• Radiotherapy primes the immune system, showing synergy with immune checkpoint inhibitors for metastatic melanoma.

Conclusions:

• Radiotherapy, particularly with larger fraction sizes, can act as an immune stimulant in melanoma.
• Combining radiotherapy with immunotherapy and hyperthermia offers potential for improved local control and abscopal effects.
• Further trials investigating the combination of radiotherapy, immunotherapy, and hyperthermia are warranted for refractory melanoma.