Ipilimumab and Stereotactic Radiosurgery with CyberKnife(®) System in Melanoma Brain Metastases: A Retrospective Monoinstitutional Experience

SIMPLE SUMMARY: Retrospective studies have shown a survival advantage in combining ipilimumab with radiotherapy in patients with melanoma brain metastases (MBMs). However, these studies did not clarify the correct timing between the two methods. The aims of our study were to demonstrate the efficacy and toxicity of stereotactic radiotherapy/radiosurgery on MBMs in combination with ipilimumab and estimate the correct timing of treatments to improve patients’ outcomes. ABSTRACT: The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife(®) System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI (p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI (p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI (p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients’ outcomes are still unclear.