No abstract

BACKGROUND Anti-PD-1+CTLA-4 therapy has revolutionized melanoma brain metastases (MBM) treatment. Prospective trials show higher response in asymptomatic versus symptomatic patients. We evaluated clinical outcomes in MBM treated with stereotactic radiosurgery (SRS) and anti-PD-1+CTLA-4. METHODS Patients were included if MBM were diagnosed and treated with SRS within 3 months of anti-PD-1+CTLA-4, and this was their last course of systemic treatment. Endpoints of this study were distant MBM control, MBM local control (LC) defined as less than 20% volume increase on follow-up MRI, and overall survival (OS) from SRS. Adverse advents were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS 29 patients with 122 MBM treated over 40 SRS sessions between 2015-2020 were identified. Median SRS dose: 24 Gy (range: 15-24). Median MBM diameter: 0.6 cm (range: 0.3-2.9). Median follow-up using reverse Kaplan-Meier (KM) method: 19.3 months (interquartile range: 14.6-38.4).Six-, twelve-, and eighteen-month KM distant MBM control rates were 51%, 42%, 42%, respectively. LC rates: 90%, 86%, 85%. OS rates: 76%, 68%, 56%. 17 patients (59%) were asymptomatic and 12 (41%) symptomatic. KM distant MBM control and OS for asymptomatic and symptomatic patients were not significant; p=0.61 and p=0.67, respectively.On univariate analysis (UVA), Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) 0-1 was associated with increased risk of distant MBM failure versus DS-GPA 3.5-4 (hazard ratio (HR): 9.8, 95% confidence interval (CI) 1.9-51.5, p=0.007). UVA showed decreased OS with increased number of organs with metastases at diagnosis (HR:12, 95% CI 2.0-83.1, p=0.0075).2 lesions (1.6%) developed symptomatic radiation necrosis requiring steroids; 10 lesions developed grade 3 edema (8%); 13 patients experienced grade 1-2 fatigue and/or headache (45%); no patients experienced grade >3 events. CONCLUSION Combination SRS and anti-PD-1+CTLA-4 in MBM shows durable intracranial control with similar outcomes between asymptomatic and symptomatic patients with acceptable toxicity. Further study is warranted.