Abstract
To determine the clinical benefits of systemic targeted agents across multiple histologies after stereotactic radiosurgery (SRS) for brain metastases. Between 2000 and 2013, 737 patients underwent upfront SRS for brain metastases. Patients were stratified by whether or not they received targeted agents with SRS. 167 (23%) received targeted agents compared to 570 (77%) that received other available treatment options. Time to event data were summarized using Kaplan-Meier plots, and the log rank test was used to determine statistical differences between groups. Patients who received SRS with targeted agents vs those that did not had improved overall survival (65% vs. 30% at 12 months, p < 0.0001), improved freedom from local failure (94% vs 90% at 12 months, p = 0.06), improved distant failure-free survival (32% vs. 18% at 12 months, p = 0.0001) and improved freedom from whole brain radiation (88% vs. 77% at 12 months, p = 0.03). Improvement in freedom from local failure was driven by improvements seen in breast cancer (100% vs 92% at 12 months, p < 0.01), and renal cell cancer (100% vs 88%, p = 0.04). Multivariate analysis revealed that use of targeted agents improved all cause mortality (HR = 0.6, p < 0.0001). Targeted agent use with SRS appears to improve survival and intracranial outcomes.
Highlights
The management options for patients with brain metastases have improved significantly over time due to effective methods for earlier detection [1], better braindirected therapies such as combined modality therapies [2], and improvements in systemic chemotherapy [3, 4].While a number of clinical trials have assessed the role of specific systemic agents for select populations of patients with brain metastases [5, 6], it remains unclear to what degree targeted systemic agents have affected the brain metastasis population as a whole
One population of particular interest is patients who receive stereotactic radiosurgery (SRS) as these patients are selected to have a www.impactjournals.com/oncotarget limited burden of disease and a longer life expectancy. It is unclear whether the development of newer systemic agents, such as targeted agents, has improved clinical endpoints after SRS for the brain metastasis population as a whole, though evidence has emerged that certain subpopulations may benefit
A recent series has shown that targeted agents improve overall survival in patients receiving SRS, and improve upon the local efficacy of SRS on brain metastases [3]
Summary
The management options for patients with brain metastases have improved significantly over time due to effective methods for earlier detection [1], better braindirected therapies such as combined modality therapies [2], and improvements in systemic chemotherapy [3, 4].While a number of clinical trials have assessed the role of specific systemic agents for select populations of patients with brain metastases [5, 6], it remains unclear to what degree targeted systemic agents have affected the brain metastasis population as a whole. One population of particular interest is patients who receive stereotactic radiosurgery (SRS) as these patients are selected to have a www.impactjournals.com/oncotarget limited burden of disease and a longer life expectancy At this time, it is unclear whether the development of newer systemic agents, such as targeted agents, has improved clinical endpoints after SRS for the brain metastasis population as a whole, though evidence has emerged that certain subpopulations may benefit. The use of targeted agents has proliferated for renal cell carcinoma [7,8,9], breast cancer [10], lung cancer [11], and melanoma [12] with improvements seen in overall survival in patients with metastatic disease Given these benefits in metastatic disease, one question that emerges is whether or not targeted agent use affects brain metastasis outcomes. To determine the clinical benefits of systemic targeted agents across multiple histologies after stereotactic radiosurgery (SRS) for brain metastases
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