title: Baseline circulating tumor cell counts significantly enhance a prognostic score for patients participating in phase I oncology trials.
abstract: BACKGROUND
  High circulating tumor cell (CTC) counts are associated with poor prognosis in several cancers. Enrollment of patients on phase I oncology trials requires a careful assessment of the potential risks and benefits. Many patients enrolled on such trials using established eligibility criteria have a short life expectancy and are less likely to benefit from trial participation. We hypothesized that the incorporation of CTC counts might improve patient selection for phase I trials.
  
  
  METHODS
  This retrospective analysis evaluated patients who had baseline CTCs enumerated prior to their starting on a phase I trial. CTCs were enumerated using the CellSearch System.
  
  
  RESULTS
  Between January 2006 and December 2009 a total of 128 patients enrolled in phase I trials had CTC counts evaluated. Higher CTC counts as a continuous variable independently correlated with risk of death in this patient population (P = 0.006). A multivariate point-based risk model was generated using CTCs as a dichotomous variable (≥3 or <3), and incorporated other established prognostic factors, including albumin <35 g/L, lactate dehydrogenase greater than upper limit of normal, and >2 metastatic sites. Comparison of receiver operating characteristic curves demonstrated that the addition of baseline CTC counts improved the performance of the prospectively validated Royal Marsden Hospital phase I prognostic score, which now identifies three risk groups (P < 0.0001): good prognosis [score 0-1, median overall survival (OS) 63.7 weeks], intermediate prognosis (score 2-3, median OS 37.3 weeks), and poor prognosis (score 4, median OS 13.4 weeks).
  
  
  CONCLUSIONS
  CTC enumeration improved the performance of a validated prognostic score to help select patients for phase I oncology trials.
authors.affiliation: Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
authors.forename: David
authors.initials: D
authors.lastname: Olmos
authors.forename: Richard D
authors.initials: RD
authors.lastname: Baird
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Yap
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.forename: Lorna
authors.initials: L
authors.lastname: Pope
authors.forename: Shahneen K
authors.initials: SK
authors.lastname: Sandhu
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.forename: Juliet
authors.initials: J
authors.lastname: Dukes
authors.forename: Dionysis
authors.initials: D
authors.lastname: Papadatos-Pastos
authors.forename: Philippa
authors.initials: P
authors.lastname: Grainger
authors.forename: Stan B
authors.initials: SB
authors.lastname: Kaye
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002452:Cell Count; D017321:Clinical Trials, Phase I as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000401:mortality; D009360:Neoplastic Cells, Circulating; D018579:Patient Selection; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis