Background: To identify the optimal sequencing and timing of immunotherapy (IT) and stereotactic radiosurgery (SRS) for melanoma brain metastases (MBMs).Methods: The elapsed days between IT and SRS were correlated with local control (LC), regional brain control (RBC), time to CNS progression (TTP CNS ), overall survival (OS), and radiation necrosis (RN). Logistic regression and Cox proportional models were used for statistical analysis.Results: Twenty-five patients with 58 MBMs underwent SRS and IT. Median follow-up was 22.7 mo (3.1-77.9 mo). A median of 2 SRS treatments of 21 Gy (range 16-24 Gy) and 4 cycles of Ipilimumab were delivered. SRS was delivered Before, After or Concurrently with IT in 9, 5, and 11 patients, respectively; 8/ 25 received SRS 30 d of IT and 17/25 were >30 d of IT. Median OS was 35.8 mo, 1-and 2-y OS was 83% and 64%, respectively, and LC was 94.8%. By timing, RBC and TTP CNS were significantly improved when SRS was delivered Conclusions: High OS was found for MBM treated with SRS and IT compared to historical reports. A significant association for improved RBC and TTP CNS was found when SRS was delivered concurrently and within 30 d of IT. Occurrence of RN was higher than SRS alone series but significantly associated with improved OS.

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Recently, modulation of immune checkpoints has risen to prominence as a means to treat a number of solid malignancies, given the durable response seen in many patients and improved side effect profile compared to conventional chemotherapeutic agents. Several classes of immune checkpoint modulators have been developed. Here, we review current monoclonal antibodies directed against immune checkpoints that are employed in practice today. We discuss the history, mechanism, indications, and clinical data for each class of therapies. Furthermore, we review the challenges to durable tumor responses that are seen in some patients and discuss possible interventions to circumvent these barriers.

Oncologic therapeutics has evolved enormously as we entered the 21st century. Unfortunately, the treatment of advanced urothelial cancer has remained unchanged over the last two decades despite a better understanding of the genetic alterations in bladder cancer. Pathways such as the PI3K/AKT3/mTOR and FGFR have been implicated in urothelial bladder cancer. However, targeted therapies have not shown proven benefit yet and are still considered investigational. Recently, researchers have been successful in manipulating the systemic immune response to mount antitumor effects in melanoma, lung cancer and lymphoma. Historically, intravesical Bacillus Calmette-Guérin immunotherapy has been highly active in nonmuscle invasive bladder cancer. Early data suggest that immune checkpoint inhibitors will soon prove to be another cornerstone in the treatment armamentarium of advanced bladder cancer.