Impact of systemic targeted agents on the clinical outcomes of patients with brain metastases

// Adam G. Johnson 1 , Jimmy Ruiz 2, 3 , Ryan Hughes 1 , Brandi R. Page 1 , Scott Isom 4 , John T. Lucas 1 , Emory R. McTyre 1 , Kristin W. Houseknecht 1 , Diandra N. Ayala-Peacock 1 , Daniel J. Bourland 1 , William H. Hinson 1 , Adrian W. Laxton 5 , Stephen B. Tatter 5 , Waldemar Debinski 6 , Kounosuke Watabe 7 , Michael D. Chan 1 1 Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA 2 Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA 3 W.G. (Bill) Hefner Veteran Administration Medical Center, Cancer Center, Salisbury, NC, USA 4 Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA 5 Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC, USA 6 Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC, USA 7 Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA Correspondence to: Adam G. Johnson, e-mail: adjohnso@wakehealth.edu Keywords: targeted agents, stereotactic radiosurgery, brain metastases, chemotherapy Received: January 29, 2015 Accepted: May 18, 2015 Published: June 01, 2015 ABSTRACT Background: To determine the clinical benefits of systemic targeted agents across multiple histologies after stereotactic radiosurgery (SRS) for brain metastases. Methods: 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. Results: 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). Conclusions: Targeted agent use with SRS appears to improve survival and intracranial outcomes.