S1054
Clinical – Sarcoma, skin cancer, malignant melanoma
ESTRO 2026
Research Hospital, Milan, Italy. 3 Department of Biomedical Sciences, Humanitas University, Milan, Italy Purpose/Objective: Melanoma brain metastases (MBMs) represent a challenging clinical scenario due to their intrinsic radioresistance and poor prognosis. While small lesions may respond favorably to effective systemic therapies, larger or symptomatic metastases often require local treatment for durable control. Stereotactic radiosurgery (SRS) and hypofractionated SRS (HSRS) are established local modalities for MBMs; however, prognostic factors influencing local control (LC), brain distant failure (BDF), and survival remain debated. This study aimed to identify clinical and treatment-related prognostic factors impacting outcomes in MBM patients treated with SRS/HSRS. Material/Methods: We retrospectively analyzed 136 consecutive melanoma patients treated between September 2010 and October 2023, encompassing 343 brain lesions. The primary endpoint was LC; secondary endpoints included BDF, progression-free survival (PFS), and overall survival (OS). Kaplan-Meier, log-rank, and Cox proportional hazards models were used to identify prognostic factors (p < 0.05). Results: Median age at MBM diagnosis was 60 years (range 30– 88). Forty percent had a single MBM, 43% had 2–4 MBMs, and 17% had >4 lesions. Extracranial (EC) metastases were present in 76.4%. Median OS from MBM diagnosis was 22 months (95% CI 15–34). LC remained excellent (1-year 93.6%, 5-year 88.4%, 10- year 88.4%). Median PFS was 13 months, and median BDF-free survival 17 months (Fig.1).
Conclusion: SRS and HSRS provide durable long-term LC in MBMs, with extracranial disease emerging as the main adverse prognostic factor for both LC and BDF. Systemic treatment after radiosurgery strongly influences OS, suggesting a synergistic benefit of integrating targeted therapy. To the best of our knowledge, this is the first study reporting 10-year outcomes in MBM patients treated with SRS/HSRS. Ongoing work focuses on radiological characterization of radionecrosis and intralesional hemorrhage to assess their potential as predictive markers for outcome and toxicity in MBM patients treated with SRS/HSRS. References: 1.Pessina F et al. (2017) World Neurosurg. 105:184– 190. 2.Williams GJ et al. (2024) Crit Rev Oncol Hematol. 202:1044623.Vaios EJ et al. (2025) JAMA Netw Open. 8(4):e254347 Keywords: melanoma brain metastases; radiosurgery
At multivariate analysis: EC metastases significantly reduced LC (p = 0.0211) (Fig 2, top panel) and BDF (p = 0.0257). Age >55 (p = 0.0368), symptoms (p = 0.012), concomitant EC metastases (p = 0.0006), systemic treatment (p = 0.0265), and type of systemic therapy (p = 0.0406) were associated with OS, as observed also at the Kaplan-Meier (Fig.2, bottom panel).
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