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

Publication date: Available online 5 December 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): 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
PurposeTo characterize the effect of concurrent stereotactic radiosurgery/stereotactic radiotherapy (SRS/SRT) and immune checkpoint inhibitors (ICI) on patient outcome and safety in patients with brain metastases (BM).Materials/Methods: We retrospectively identified metastatic non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) patients who had BM treated with SRS/SRT from 2010-2016 without prior whole brain radiotherapy (WBRT). We included SRS/SRT patients who were treated with anti-CTLA4 (ipilimumab) and anti-PD-1 (nivolumab, pembrolizumab). Patients who were given ICI on active or unreported clinical trials were excluded, and concurrent ICI was defined as given within 2 weeks of SRS/SRT. Patients were managed with SRS/SRT, SRS/SRT with non-concurrent ICI, and SRS/SRT with concurrent ICI. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier survival curves, and cox proportional hazard models were used for multivariate analysis. Logistic regression was used to identify predictors of acute neurologic toxicity, immune-related adverse events (irAEs), and new BM.Results260 patients were treated with SRS/SRT to 623 brain metastases. 181 were treated with SRS/SRT only and 79 with SRS/SRT and ICI, with 35% of patients treated with concurrent SRS/SRT and ICI. Concurrent ICI was not associated with increased rates of irAEs or acute neurologic toxicity and predicted for a decreased likelihood of developing ≥ 3 new BM following SRS/SRT (p=0.045, OR 0.337). Median OS for patients treated with SRS/SRT, SRS/SRT and non-concurrent ICI, and SRS/SRT with concurrent ICI was 12.9, 14.5, and 24.7 months respectively. Concurrent SRS/SRT and ICI was associated with improved OS compared to SRS/SRT only (p=0.002, HR 2.69) and compared to non-concurrent SRS/SRT and ICI (p=0.006, HR 2.40) on multivariate analyses. The OS benefit of Concurrent SRS/SRT and ICI was significant in comparison to patients treated with SRS/SRT pre (p=0.002, HR 3.82) or post (p=0.021, HR 2.64) ICI.ConclusionDelivering SRS/SRT with concurrent ICI may be associated with decreased incidence of new BM and favorable survival outcomes without increased rates of adverse events.

Teaser

Radiation is hypothesized to augment the immunogenicity of tumor cells. We retrospectively evaluated survival outcomes, incidence of new brain metastases, and treatment-related adverse events in patients who received stereotactic radiosurgery for brain metastases with concurrent immune checkpoint inhibition, with non-concurrent immune checkpoint inhibition, and with stereotactic radiosurgery alone. Delivering SRS with concurrent ICI may be associated with decreased incidence of new BM and favorable survival outcomes without increased rates of adverse events.


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