Factors Associated with Hemorrhage of Melanoma Brain Metastases after Stereotactic Radiosurgery in the Era of Targeted/Immune Checkpoint Inhibitor Therapies

SIMPLE SUMMARY: Melanoma brain metastases (MBM) have a high propensity for hemorrhage (HA) after treatment. Our retrospective analysis evaluated factors associated with HA of MBM after robotic stereotactic radiosurgery (SRS) in the era of modern systemic therapy, and to the best of our knowledge, this is the first study focusing on this side effect. A total of 55 patients with 279 MBM were treated. The use of anticoagulants was the only predictive factor, both for radiologically evident HA and HA causing grade 3 toxicity. The interval between the administration of systemic therapy and SRS was also significant with regard to HA causing grade 1 toxicity, but it appears that the combination was safe, at least concerning grade 3 toxicity. We believe that our study is a useful contribution to the current literature, as it provides insights regarding the factors that correlate with HA. ABSTRACT: We aimed to evaluate the factors associated with hemorrhage (HA) of melanoma brain metastases (MBM) after Cyberknife stereotactic radiosurgery (SRS) in the modern era of systemic therapy. A total of 55 patients with 279 MBM were treated in 93 fractions. The median age, SRS dose, radiological follow-up, and time to HA were 60.4 years, 20 Gy, 17.7 months, and 10.7 months, respectively. Radiologically evident HA was documented in 47 (16.8%) metastases. Of the 55 patients, 25 (45.4%) suffered an HA. Among those, HA caused grade 3 toxicity in 10 patients (40%) and grade 1 symptoms in 5 patients (20%). Ten patients (40%) with HA experienced no toxicity. Logistic regression revealed the use of anticoagulants and the administration of systemic therapy within 7/15 days from SRS to be predictive for HA. When considering the HA causing grade 3 symptomatology, only the use of anticoagulants was significant, with the delivery of whole brain radiation therapy (WBRT) before the HA narrowly missing statistical significance. Our retrospective analysis showed that the administration of modern systemic therapy within 7/15 days from SRS may contribute to HA of MBM, though it appears safe, at least concerning grade 3 toxicity. The use of anticoagulants by the time of SRS significantly increased the risk of HA.