Impact of Sequencing Radiation Therapy and Immune Checkpoint Inhibitors in the Treatment of Melanoma Brain Metastases

• DOI: 10.1016/j.ijrobp.2020.01.043
• Publication Date: 2020-02-11T18:52:42Z
• Authors: Daniel A. Pomeran...; Tahseen H. Nasti; Benjamin Izar; Robert H. Press; Maxwell Xu; Lindsey Lowder; Laura Kallay; Manali Rupji; Havi Rosen; Jing Su; Walter Curran; Jeffrey Olson; Brent Weinberg; Matthew Schniederjan; Stewart Neill; David Lawson; Jeanne Kowalski; Mohammad K. Khan; Soma Sengupta
• Keywords: Immune checkpoint; Combination therapy

PurposeMelanoma brain metastases (MBM) occur in ∼50% of melanoma patients. Although both radiation therapy (RT) and immune checkpoint inhibitor (ICI) are used alone or combination for MBM treatment, the role this how these treatments could best be sequenced remains unclear.Methods MaterialsWe conducted a retrospective analysis patients with resected who underwent treatment RT, ICI, RT ICI. Among latter, we specifically investigated differential gene expression via RNA-sequencing between received first then ICI (RT → ICI) versus (ICI RT). We glycoprotein-transduced syngeneic mouse model validation experiments.ResultsWe found that MBM, confers superior survival compared alone. Specifically, was RT. Transcriptome revealed cohort demonstrated deregulation genes involved apoptotic signaling key modulators inflammation most implicated nuclear factor kappa-light-chain-enhancer activated B cells signaling. In preclinical model, showed followed by anti-programmed death-ligand 1 to reverse sequence therapy, supporting observations made MBM.ConclusionsOur study provides initial insights into optimal after surgical resection. Prospective studies examining necessary, our contributes rationale pursue these. Melanoma unclear. experiments. MBM. Our