Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: A two-arm pilot study evaluating clinical outcomes and immunological correlates Journal Article
| Authors: | Jansen, C. S.; Pagadala, M. S.; Cardenas, M. A.; Prabhu, R. S.; Goyal, S.; Zhou, C.; Chappa, P.; Vo, B. T.; Ye, C.; Hopkins, B.; Zhong, J.; Klie, A.; Daniels, T.; Admassu, M.; Green, I.; Pfister, N. T.; Neill, S. G.; Switchenko, J. M.; Prokhnevska, N.; Hoang, K. B.; Torres, M. A.; Logan, S.; Olson, J. J.; Nduom, E. K.; del Balzo, L.; Patel, K.; Burri, S. H.; Asher, A. L.; Wilkinson, S.; Lake, R.; Kesarwala, A. H.; Higgins, K. A.; Patel, P.; Dhere, V.; Sowalsky, A. G.; Carter, H.; Khan, M. K.; Kissick, H.; Buchwald, Z. S. |
| Article Title: | Pre-operative stereotactic radiosurgery and peri-operative dexamethasone for resectable brain metastases: A two-arm pilot study evaluating clinical outcomes and immunological correlates |
| Abstract: | 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. © The Author(s) 2024. |
| Keywords: | adult; cancer survival; clinical article; controlled study; human tissue; treatment outcome; aged; middle aged; cancer surgery; retrospective studies; human cell; overall survival; clinical trial; fatigue; paresthesia; cancer recurrence; drug efficacy; drug safety; multimodality cancer therapy; cancer radiotherapy; combined modality therapy; brain radiation; drug megadose; brain tumor; brain neoplasms; prospective study; prospective studies; cd8+ t lymphocyte; cd8-positive t-lymphocytes; low drug dose; cohort analysis; dexamethasone; retrospective study; confusion; immunology; antigen; brain; pilot study; pilot projects; radiosurgery; brain metastasis; muscle weakness; immunomodulation; cognitive defect; safety; headache; cell density; stereotactic radiosurgery; preoperative treatment; somnolence; tremor; visual disorder; therapy; antigen presenting cell; radiation necrosis; transcription factor 7; brain edema; perioperative care; programmed death 1 receptor; gait disorder; clinical outcome; dysarthria; procedures; disease incidence; cancer prognosis; dysphasia; cell component; humans; human; male; female; article; brain dysfunction; hepatitis a virus cellular receptor 2; altered state of consciousness; scalp pain |
| Journal Title: | Nature Communications |
| Volume: | 15 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-10-14 |
| Start Page: | 8854 |
| Language: | English |
| DOI: | 10.1038/s41467-024-53034-6 |
| PUBMED: | 39402027 |
| PROVIDER: | scopus |
| PMCID: | PMC11473782 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
