Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma

Linda Chen, Jacqueline Douglass, Lawrence Kleinberg, Xiaobu Ye, Ariel E. Marciscano, Patrick M. Forde, Julie Brahmer, Evan Lipson, William Sharfman, Hans Hammers, Jarushka Naidoo, Chetan Bettegowda, Michael Lim, Kristin J. Redmond

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65 Scopus citations

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). 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. 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). 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.

Original languageEnglish (US)
Pages (from-to)916-925
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume100
Issue number4
DOIs
StatePublished - Mar 15 2018

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Chen, L., Douglass, J., Kleinberg, L., Ye, X., Marciscano, A. E., Forde, P. M., Brahmer, J., Lipson, E., Sharfman, W., Hammers, H., Naidoo, J., Bettegowda, C., Lim, M., & Redmond, K. J. (2018). Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma. International Journal of Radiation Oncology Biology Physics, 100(4), 916-925. https://doi.org/10.1016/j.ijrobp.2017.11.041