Matthew N. Mills

Purpose Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual checkpoint blockade improves outcomes over dual-checkpoint blockade alone is unknown. We evaluated clinical outcomes of patients with MBM receiving ICI with nivolumab and ipilimumab, with and without SRS. Methods 49 patients with 158 MBM receiving nivolumab and ipilimumab for untreated MBM between 2015 and 2022 were identified at our institution. Patient and tumor characteristics including age, Karnofsky Performance Status (KPS), presence of symptoms, cancer history, MBM burden, and therapy course were recorded. Outcomes measured from initiation of MBM-directed therapy included overall survival (OS), local control (LC), and distant intracranial control (DIC). Time-to-event analysis was conducted with the Kaplan–Meier method. Results 25 patients with 74 MBM received ICI alone, and 24 patients with 84 MBM received concurrent SRS. Median follow-up was 24 months. No differences in age (p = 0.96), KPS (p = 0.85), presence of symptoms (p = 0.79), prior MBM (p = 0.68), prior MBM-directed surgery (p = 0.96) or SRS (p = 0.68), MBM size (p = 0.67), or MBM number (p = 0.94) were seen. There was a higher rate of nivolumab and ipilimumab course completion in the SRS group (54% vs. 24%; p = 0.029). The SRS group received prior immunotherapy more often than the ICI alone group (54% vs. 8.0%; p < 0.001). There was no significant difference in 1-year OS (72% vs. 71%, p = 0.20) and DIC (63% v 51%, p = 0.26) between groups. The SRS group had higher 1-year LC (92% vs. 64%; p = 0.002). On multivariate analysis, LC was improved with combination therapy (AHR 0.38, p = 0.01). Conclusion In our analysis, patients who received SRS with nivolumab and ipilimumab had superior LC without increased risk of toxicity or compromised immunotherapy treatment completion despite the SRS cohort having higher rates of prior immunotherapy. Further prospective study of combination nivolumab and ipilimumab with SRS is warranted.

Integration of locoregional therapies such as stereotactic body radiation therapy (SBRT) is increasing in the treatment of hepatocellular carcinoma (HCC), the most common primary cancer of the liver. A 68-year-old man with hepatitis C was diagnosed with American Joint Committee on Cancer stage 2 (cT2N0M0), Child-Pugh class A, multifocal HCC. He completed adaptive MR-guided stereotactic body radiation therapy (MRgSBRT) for a total dose of 50 Gy in 5 fractions. At the 3-month follow-up, a three-phase abdominal CT showed a decrease in the size of the treated lesion and a new gastric fistula was noted. He started a proton pump inhibitor and remained under close observation. At the 6-month follow-up, imaging showed a decrease in tumor size with continued evidence of a contained fistula. Severe side effects are possible following MRgSBRT to the liver, even with the utilization of adaptive treatment, highlighting the importance of attention to high-dose isodose lines near normal tissues and adherence to dose constraints.