title: Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT).
abstract: The selection of patients for oligometastasis-directed ablative therapy remains a challenge. The authors report on clinical and molecular predictors of survival from a stereotactic body radiotherapy (SBRT) dose-escalation trial for oligometastases.
  
  
  
  Patients who had from 1 to 5 metastases, a life expectancy of >3 months, and a Karnofsky performance status of >60 received escalating SBRT doses to all known cancer sites. Time to progression, progression-free survival, and overall survival (OS) were calculated at the completion of SBRT, and clinical predictors of OS were modeled. Primary tumor microRNA expression was analyzed to identify molecular predictors of OS.
  
  
  
  Sixty-one evaluable patients were enrolled from 2004 to 2009. The median follow-up was 2.3 years for all patients (range, 0.2-9.3 years) and 6.8 years for survivors (range, 2.0-9.3 years). The median, 2-year, and 5-year estimated OS were 2.4 years, 57%, and 32%, respectively. The rate of progression after SBRT was associated with an increased risk of death (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.24-1.82). The time from initial cancer diagnosis to metastasis (HR, 0.98; 95% CI, 0.98-0.99), the time from metastasis to SBRT (HR, 0.98; 95% CI, 0.98-0.99), and breast cancer histology (HR, 0.12; 95% CI, 0.07-0.37) were significant predictors of OS. In an exploratory analysis, a candidate classifier using expression levels of 3 microRNAs (miR-23b, miR-449a, and miR-449b) predicted survival among 17 patients who had primary tumor microRNA expression data available.
  
  
  
  A subset of oligometastatic patients achieves long-term survival after metastasis-directed SBRT. Clinical features and primary tumor microRNA expression profiling, if validated in an independent dataset, may help select oligometastatic patients most likely to benefit from metastasis-directed therapy. Cancer 2016;122:2242-50. © 2016 American Cancer Society.
authors.affiliation: Department of Radiation and Cellular Oncology, the University of Chicago, Chicago, Illinois.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Wong
authors.affiliation: Department of Public Health Sciences, the University of Chicago, Chicago, Illinois.
authors.forename: Sydeaka P
authors.initials: SP
authors.lastname: Watson
authors.affiliation: Department of Radiation and Cellular Oncology, the University of Chicago, Chicago, Illinois.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Pitroda
authors.affiliation: Department of Radiation and Cellular Oncology, the University of Chicago, Chicago, Illinois.
authors.forename: Christina H
authors.initials: CH
authors.lastname: Son
authors.affiliation: Department of Radiation and Cellular Oncology, the University of Chicago, Chicago, Illinois.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Das
authors.affiliation: Department of Surgery, the University of Chicago, Chicago, Illinois.
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Stack
authors.affiliation: Department of Surgery, the University of Chicago, Chicago, Illinois.
authors.forename: Abhineet
authors.initials: A
authors.lastname: Uppal
authors.affiliation: Department of Surgery, the University of Chicago, Chicago, Illinois.
authors.forename: Go
authors.initials: G
authors.lastname: Oshima
authors.affiliation: Department of Radiation and Cellular Oncology, the University of Chicago, Chicago, Illinois.|Ludwig Center for Metastasis Research, the University of Chicago, Chicago, Illinois.
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Khodarev
authors.affiliation: Department of Radiation Oncology, Duke University, Durham, North Carolina.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Salama
authors.affiliation: Department of Radiation and Cellular Oncology, the University of Chicago, Chicago, Illinois.|Ludwig Center for Metastasis Research, the University of Chicago, Chicago, Illinois.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.affiliation: Department of Radiation and Cellular Oncology, the University of Chicago, Chicago, Illinois.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Chmura
mesh_terms: D014408:Biomarkers, Tumor; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000175:diagnosis* / Q000401:mortality* / Q000532:radiotherapy; D011379:Prognosis; D016016:Proportional Hazards Models; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: biomarker; classifier; microRNA; oligometastases; stereotactic body radiotherapy