title: Developing an objective marker to optimize patient selection and predict survival benefit in early-phase cancer trials.
abstract: BACKGROUND
  Several prognostic indices have been devised to optimize patient selection for phase 1 oncology trials with no consensus as to the optimal score and none qualifying as a marker of treatment response.
  
  
  METHODS
  Multivariate predictors of overall survival (OS) were tested on 118 referred patients to develop the Hammersmith Score (HS). The score's ability to predict OS, progression-free survival (PFS), and 90-day mortality (90DM) was compared with other prognostic indices. Changes in HS were recalculated during treatment.
  
  
  RESULTS
  Albumin<35 g/L, lactate dehydrogenase>450 U/L, and sodium<135 mmol/L emerged as independent prognostic factors. These were used with equal weighting to devise the HS, a compound prognostic index ranging from 0 to 3. High (HS=2-3) score predicted worse OS (hazard ratio [HR]=6.5, P<.001), PFS (HR=2.8, P=.01), and 90DM (OR=9.0, P<.001). HS was a more accurate multivariate predictor of OS (HR=6.4, P<.001, C-index=0.72), PFS (HR=2.7, P=.03), and 90DM (area under the ROC curve 0.703) compared with other scores. Worsening of the HS during treatment predicted for shorter OS (P<.001). HS retained prognostic and predictive ability following external validation.
  
  
  CONCLUSIONS
  HS is a simple, validated index to optimize patient selection and predict survival benefit from phase 1 oncology treatments. Prospective validation is ongoing.
authors.affiliation: Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors.forename: Chara
authors.initials: C
authors.lastname: Stavraka
authors.forename: David J
authors.initials: DJ
authors.lastname: Pinato
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Turnbull
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Flynn
authors.forename: Martin D
authors.initials: MD
authors.lastname: Forster
authors.forename: Sean M
authors.initials: SM
authors.lastname: O'Cathail
authors.forename: Sayed
authors.initials: S
authors.lastname: Babar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Seckl
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Kristeleit
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Blagden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000032:analysis; D017321:Clinical Trials, Phase I as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000401:mortality* / Q000628:therapy; D018579:Patient Selection; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012964:Sodium / Q000097:blood
chemical_list: D000418:Albumins; D012964:Sodium; D007770:L-Lactate Dehydrogenase
keywords: albumin; outcome; phase 1 trial; prognostic score; survival