Amy Le1, Homan Mohammadi2, Toka Mohammed1, Heather Burney3, Yong Zang3, Douglas Frye4, Kevin Shiue1, Tim Lautenschlaeger5, James Miller6. 1. Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA. 2. Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. 3. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA. 4. Department of Radiation Oncology, Indiana University Health Bloomington Hospital, Bloomington, IN, USA. 5. Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA. timlaut@iupui.edu. 6. Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Abstract
INTRODUCTION: The treatment of brain metastases with stereotactic radiosurgery (SRS) in combination with immune checkpoint inhibitors (ICI) has become more common in recent years, but there is a lack of prospective data on cancer control outcomes when these therapies are administered concurrently. METHODS: Data were retrospectively reviewed for patients with non-small cell lung cancer (NSCLC) and melanoma brain metastases treated with SRS at a single institution from May 2008 to January 2017. A parametric proportional hazard model is used to detect the effect of concurrent ICI within 30, 60, or 90 days of ICI administration on local control and distant in-brain control. Other patient and lesion characteristics are treated as covariates and adjusted in the regression. A frailty term is added in the baseline hazard to capture the within-patient correlation. RESULTS: We identified 144 patients with 477 total lesions, including 95 NSCLC patients (66.0%), and 49 (34.0%) melanoma patients. On multivariate analysis, concurrent SRS and ICI (SRS within 30 days of ICI administration) was not associated with local control but was associated with distant brain control. When controlling for prior treatment to lesion, number of lesions, and presence of extracranial metastases, patients receiving this combination had a statistically significant decrease in distant brain failure compared to patients that received non-concurrent ICI or no ICI (HR 0.15; 95% CI 0.05-0.47, p = 0.0011). CONCLUSION: Concurrent ICI can enhance the efficacy of SRS. Prospective studies would allow for stronger evidence to support the impact of concurrent SRS and ICI on disease outcomes.
INTRODUCTION: The treatment of brain metastases with stereotactic radiosurgery (SRS) in combination with immune checkpoint inhibitors (ICI) has become more common in recent years, but there is a lack of prospective data on cancer control outcomes when these therapies are administered concurrently. METHODS: Data were retrospectively reviewed for patients with non-small cell lung cancer (NSCLC) and melanoma brain metastases treated with SRS at a single institution from May 2008 to January 2017. A parametric proportional hazard model is used to detect the effect of concurrent ICI within 30, 60, or 90 days of ICI administration on local control and distant in-brain control. Other patient and lesion characteristics are treated as covariates and adjusted in the regression. A frailty term is added in the baseline hazard to capture the within-patient correlation. RESULTS: We identified 144 patients with 477 total lesions, including 95 NSCLC patients (66.0%), and 49 (34.0%) melanoma patients. On multivariate analysis, concurrent SRS and ICI (SRS within 30 days of ICI administration) was not associated with local control but was associated with distant brain control. When controlling for prior treatment to lesion, number of lesions, and presence of extracranial metastases, patients receiving this combination had a statistically significant decrease in distant brain failure compared to patients that received non-concurrent ICI or no ICI (HR 0.15; 95% CI 0.05-0.47, p = 0.0011). CONCLUSION: Concurrent ICI can enhance the efficacy of SRS. Prospective studies would allow for stronger evidence to support the impact of concurrent SRS and ICI on disease outcomes.
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