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Title: Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCPmore » provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.« less
Authors:
 [1] ;  [2] ;  [3] ;  [1] ;  [2] ;  [3] ; ; ; ; ; ; ; ;  [4] ;  [5] ;  [3] ;  [4]
  1. Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States)
  2. (Urology), Duke University School of Medicine, Durham, North Carolina (United States)
  3. (United States)
  4. Myriad Genetics, Inc, Salt Lake City, Utah (United States)
  5. Department of Radiation Oncology, Durham VA Medical Center, Durham, North Carolina (United States)
Publication Date:
OSTI Identifier:
22267826
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 86; Journal Issue: 5; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANDROGENS; ANTIGENS; APPROXIMATIONS; BIOPSY; CELL CYCLE; DIAGNOSIS; EXTERNAL BEAM RADIATION THERAPY; GENES; HAZARDS; MORTALITY; NEOPLASMS; PATIENTS; PROSTATE; RNA