Research Papers:

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

Adam G. Johnson _, Jimmy Ruiz, Ryan Hughes, Brandi R. Page, Scott Isom, John T. Lucas, Emory R. McTyre, Kristin W. Houseknecht, Diandra N. Ayala-Peacock, J. Daniel Bourland, William H. Hinson, Adrian W. Laxton, Stephen B. Tatter, Waldemar Debinski, Kounosuke Watabe and Michael D. Chan

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Oncotarget. 2015; 6:18945-18955. https://doi.org/10.18632/oncotarget.4153

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Adam G. Johnson1, Jimmy Ruiz2,3, Ryan Hughes1, Brandi R. Page1, Scott Isom4, John T. Lucas1, Emory R. McTyre1, Kristin W. Houseknecht1, Diandra N. Ayala-Peacock1, Daniel J. Bourland1, William H. Hinson1, Adrian W. Laxton5, Stephen B. Tatter5, Waldemar Debinski6, Kounosuke Watabe7, Michael D. Chan1

1Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA

2Department of Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA

3W.G. (Bill) Hefner Veteran Administration Medical Center, Cancer Center, Salisbury, NC, USA

4Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

5Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC, USA

6Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston-Salem, NC, USA

7Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA

Correspondence to:

Adam G. Johnson, e-mail: [email protected]

Keywords: targeted agents, stereotactic radiosurgery, brain metastases, chemotherapy

Received: January 29, 2015     Accepted: May 18, 2015     Published: June 01, 2015


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.

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