This open-label, prospective, single-arm Phase II trial explores whether adding stereotactic body radiotherapy (SBRT) or hypofractionated radiotherapy to oligoprogressive lesions can help delay disease progression in patients with metastatic melanoma. Participants may have up to ten extracranial oligoprogressive sites, with no upper limit on the total number of metastatic lesions. The study aims to assess whether targeting these progressing sites with focused radiotherapy can extend progression-free survival in this patient population.

This study evaluates the use of stereotactic body radiotherapy (SBRT) or hypofractionated radiotherapy in patients with metastatic melanoma who have up to 10 extracranial oligoprogressive lesions while receiving first-line systemic therapy. Oligoprogression refers to progression at a limited number of sites, while the remaining disease remains controlled by systemic treatment.

Participants will continue their current systemic therapy and receive SBRT or hypofractionated radiotherapy to all oligoprogressive lesions. The study will assess whether this approach can delay overall disease progression and extend the duration of benefit from ongoing systemic therapy.

Imaging will be used to monitor disease progression, and blood samples will be collected at baseline, after radiation, and at disease progression for exploratory analysis. Additional outcomes include overall survival, time on current therapy, toxicity, quality of life, and out-of-field response.

Inclusion Criteria:

• Age 18 or older
• ECOG 0-2
• Willing and able to provide informed consent
• Metastatic melanoma detected on imaging and clinically confirmed.
• Treated with first line immunotherapy or BRAF inhibitors.
• No upper limit to the number of total metastatic sites, but a maximum of ten progressive metastatic sites, inclusive of primary disease and metastatic lesions, all of which must be extra cranial.
• Patients who had any prior radiation therapy near or overlapping with the oligoprogressive sites are allowed to enroll.
• All sites of oligoprogression that can be safely treated with SBRT or hypofractionated radiotherapy.

Exclusion Criteria:

• >10 extracranial sites of progressive disease.
• Pregnancy.
• Leptomeningeal disease.
• Serious medical comorbidities precluding radiotherapy, such as ataxia-telangiectasia or scleroderma.
• Prior radiotherapy near the oligoprogressive lesion precluding SBRT or hypofractionated radiotherapy due to exceeding OAR tolerance.
• Any psychological, sociological or geographical issue potentially hampering compliance with the study.
• Any other condition which in the judgment of the investigator would make the patient inappropriate for entry into this study.