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Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma.
- Source :
-
International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2018 Mar 15; Vol. 100 (4), pp. 916-925. Date of Electronic Publication: 2017 Dec 05. - Publication Year :
- 2018
-
Abstract
- Purpose: To characterize the effect of concurrent stereotactic radiosurgery-stereotactic radiation therapy (SRS-SRT) and immune checkpoint inhibitors on patient outcomes and safety in patients with brain metastases (BMs).<br />Methods and Materials: We retrospectively identified metastatic non-small cell lung cancer, melanoma, and renal cell carcinoma patients who had BMs treated with SRS-SRT from 2010 to 2016 without prior whole-brain radiation therapy. We included SRS-SRT patients who were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) and anti-programmed cell death protein 1 receptor (nivolumab, pembrolizumab). Patients who were given immune checkpoint inhibitors on active or unreported clinical trials were excluded, and concurrent immune checkpoint inhibition (ICI) was defined as ICI given within 2 weeks of SRS-SRT. Patients were managed with SRS-SRT, SRS-SRT with nonconcurrent ICI, or SRS-SRT with concurrent ICI. Progression-free survival and overall survival (OS) were estimated using Kaplan-Meier survival curves, and Cox proportional hazards models were used for multivariate analysis. Logistic regression was used to identify predictors of acute neurologic toxicity, immune-related adverse events, and new BMs.<br />Results: A total of 260 patients were treated with SRS-SRT to 623 BMs. Of these patients, 181 were treated with SRS-SRT alone, whereas 79 received SRS-SRT and ICI, 35% of whom were treated with concurrent SRS-SRT and ICI. Concurrent ICI was not associated with increased rates of immune-related adverse events or acute neurologic toxicity and predicted for a decreased likelihood of the development of ≥3 new BMs after SRS-SRT (P=.045; odds ratio, 0.337). Median OS for patients treated with SRS-SRT, SRS-SRT with nonconcurrent ICI, and SRS-SRT with concurrent ICI was 12.9 months, 14.5 months, and 24.7 months, respectively. SRS-SRT with concurrent ICI was associated with improved OS compared with SRS-SRT alone (P=.002; hazard ratio [HR], 2.69) and compared with nonconcurrent SRS-SRT and ICI (P=.006; HR, 2.40) on multivariate analysis. The OS benefit of concurrent SRS-SRT and ICI was significant in comparison with patients treated with SRS-SRT before ICI (P=.002; HR, 3.82) or after ICI (P=.021; HR, 2.64).<br />Conclusions: Delivering SRS-SRT with concurrent ICI may be associated with a decreased incidence of new BMs and favorable survival outcomes without increased rates of adverse events.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Aged
Antibodies, Monoclonal, Humanized therapeutic use
Brain Neoplasms mortality
Carcinoma, Non-Small-Cell Lung mortality
Carcinoma, Non-Small-Cell Lung secondary
Carcinoma, Renal Cell secondary
Combined Modality Therapy adverse effects
Combined Modality Therapy methods
Humans
Immunotherapy adverse effects
Immunotherapy mortality
Ipilimumab therapeutic use
Melanoma mortality
Melanoma secondary
Middle Aged
Nivolumab therapeutic use
Progression-Free Survival
Radiosurgery adverse effects
Radiosurgery mortality
Retrospective Studies
Survival Analysis
Antineoplastic Agents, Immunological therapeutic use
Brain Neoplasms secondary
Brain Neoplasms therapy
Carcinoma, Non-Small-Cell Lung therapy
Carcinoma, Renal Cell therapy
Immunotherapy methods
Kidney Neoplasms pathology
Lung Neoplasms pathology
Melanoma therapy
Radiosurgery methods
Subjects
Details
- Language :
- English
- ISSN :
- 1879-355X
- Volume :
- 100
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of radiation oncology, biology, physics
- Publication Type :
- Academic Journal
- Accession number :
- 29485071
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2017.11.041