Impact of Sequencing Radiation Therapy and Immune Checkpoint Inhibitors in the Treatment of Melanoma Brain Metastases
| Autor: | Matthew Schniederjan, Jeffrey J. Olson, Havi Rosen, Benjamin Izar, Brent D. Weinberg, Daniel Pomeranz Krummel, Robert H. Press, Mohammad K. Khan, Maxwell Xu, David H. Lawson, Manali Rupji, Lindsey Lowder, Soma Sengupta, Stewart G. Neill, Jeanne Kowalski, Jing Su, Tahseen H. Nasti, Walter J. Curran, Laura Kallay |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Time Factors medicine.medical_treatment Inflammation Article 030218 nuclear medicine & medical imaging Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Text mining Cell Line Tumor Gene expression polycyclic compounds medicine Animals Humans Radiology Nuclear Medicine and imaging Prospective cohort study Immune Checkpoint Inhibitors Melanoma Retrospective Studies Radiation Brain Neoplasms business.industry medicine.disease Combined Modality Therapy Radiation therapy Oncology Apoptosis 030220 oncology & carcinogenesis Cancer research medicine.symptom business hormones hormone substitutes and hormone antagonists |
| Zdroj: | Int J Radiat Oncol Biol Phys |
| ISSN: | 0360-3016 |
| Popis: | Purpose Melanoma brain metastases (MBM) occur in ∼50% of melanoma patients. Although both radiation therapy (RT) and immune checkpoint inhibitor (ICI) are used alone or in combination for MBM treatment, the role of this combination and how these treatments could best be sequenced remains unclear. Methods and Materials We conducted a retrospective analysis of patients with resected MBM who underwent treatment with RT, ICI, or a combination of RT and ICI. Among the latter, we specifically investigated the differential gene expression via RNA-sequencing between patients who received RT first then ICI (RT → ICI) versus ICI first then RT (ICI → RT). We used a glycoprotein-transduced syngeneic melanoma mouse model for validation experiments. Results We found that for patients with resected MBM, a combination of RT and ICI confers superior survival compared with RT alone. Specifically, we found that RT → ICI was superior compared with ICI → RT. Transcriptome analysis of resected MBM revealed that the RT → ICI cohort demonstrated deregulation of genes involved in apoptotic signaling and key modulators of inflammation that are most implicated in nuclear factor kappa-light-chain-enhancer of activated B cells signaling. In a preclinical model, we showed that RT followed by anti-programmed death-ligand 1 therapy was superior to the reverse sequence of therapy, supporting the observations we made in patients with MBM. Conclusions Our study provides initial insights into the optimal sequence of RT and ICI in the treatment of MBM after surgical resection. Prospective studies examining the best sequence of RT and ICI are necessary, and our study contributes to the rationale to pursue these. |
| Databáze: | OpenAIRE |
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