Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: a two-arm pilot study evaluating clinical outcomes and immunological correlates.

Autor: Jansen CS; Department of Urology, Emory University, Atlanta, USA., Pagadala MS; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA., Cardenas MA; Department of Urology, Emory University, Atlanta, USA., Prabhu RS; Southeast Radiation Oncology Group, Levine Cancer Institute, Atrium Health, Charlotte, USA., Goyal S; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, USA., Zhou C; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Chappa P; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Vo BT; Department of Urology, Emory University, Atlanta, USA., Ye C; Department of Urology, Emory University, Atlanta, USA., Hopkins B; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Zhong J; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Klie A; Biomedical Sciences Program, University of California San Diego, La Jolla, USA., Daniels T; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Admassu M; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Green I; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Pfister NT; Department of Radiation Oncology, University of Alabama Birmingham, Birmingham, AL, USA., Neill SG; Department of Pathology, Emory University, Atlanta, USA., Switchenko JM; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, USA., Prokhnevska N; Department of Urology, Emory University, Atlanta, USA., Hoang KB; Winship Cancer Institute, Emory University, Atlanta, USA.; Department of Neurosurgery, Emory University, Atlanta, USA., Torres MA; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Logan S; Department of Pathology, Nationwide Children's Hospital, Columbus, USA., Olson JJ; Winship Cancer Institute, Emory University, Atlanta, USA.; Department of Neurosurgery, Emory University, Atlanta, USA., Nduom EK; Winship Cancer Institute, Emory University, Atlanta, USA.; Department of Neurosurgery, Emory University, Atlanta, USA., Del Balzo L; Department of Urology, Emory University, Atlanta, USA., Patel K; Kaiser Permanente, Atlanta, USA., Burri SH; Southeast Radiation Oncology Group, Levine Cancer Institute, Atrium Health, Charlotte, USA., Asher AL; Neuroscience Institute, Atrium Health, Charlotte, USA., Wilkinson S; Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, USA., Lake R; Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, USA., Kesarwala AH; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Higgins KA; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Patel P; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Dhere V; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Sowalsky AG; Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, USA., Carter H; Department of Medicine, Division of Medical Genetics, University of California San Diego, La Jolla, USA., Khan MK; Department of Radiation Oncology, Emory University, Atlanta, USA.; Winship Cancer Institute, Emory University, Atlanta, USA., Kissick H; Department of Urology, Emory University, Atlanta, USA. haydn.kissick@emory.edu.; Department of Microbiology and Immunology, Emory University, Atlanta, USA. haydn.kissick@emory.edu., Buchwald ZS; Department of Radiation Oncology, Emory University, Atlanta, USA. zbuchwa@emory.edu.; Winship Cancer Institute, Emory University, Atlanta, USA. zbuchwa@emory.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 14; Vol. 15 (1), pp. 8854. Date of Electronic Publication: 2024 Oct 14.
DOI: 10.1038/s41467-024-53034-6
Abstrakt: Enhancing the efficacy of immunotherapy in brain metastases (BrM) requires an improved understanding of the immune composition of BrM and how this is affected by radiation and dexamethasone. Our two-arm pilot study (NCT04895592) allocated 26 patients with BrM to either low (Arm A) or high (Arm B) dose peri-operative dexamethasone followed by pre-operative stereotactic radiosurgery (pSRS) and resection (n= 13 per arm). The primary endpoint, a safety analysis at 4 months, was met. The secondary clinical endpoints of overall survival, distant brain failure, leptomeningeal disease and local recurrence at 12-months were 66%, 37.3%, 6%, and 0% respectively and were not significantly different between arms (p= 0.7739, p= 0.3884, p= 0.3469). Immunological data from two large retrospective BrM datasets and confirmed by correlates from both arms of this pSRS prospective trial revealed that BrM CD8 T cells were composed of predominantly PD1+ TCF1+ stem-like and PD1+ TCF1-TIM3+ effector-like cells. Clustering of TCF1+ CD8 T cells with antigen presenting cells in immune niches was prognostic for local control, even without pSRS. Following pSRS, CD8 T cell and immune niche density were transiently reduced compared to untreated BrM, followed by a rebound 6+ days post pSRS with an increased frequency of TCF1- effector-like cells. In sum, pSRS is safe and therapeutically beneficial, and these data provide a framework for how pSRS may be leveraged to maximize intracranial CD8 T cell responses.
(© 2024. The Author(s).)
Databáze: MEDLINE
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