title: A prognostic index for progression-free survival in malignant mesothelioma with application to the design of phase II trials: a combined analysis of 10 EORTC trials.
abstract: OBJECTIVE
  For cytostatic agents or when the response assessment is difficult, adaptations to phase II designs may allow a better assessment of therapeutic activity: first by using the progression-free survival rate (PFSR) as primary end-point instead of the response rate, and second by considering progression-free survival (PFS) risk groups based on a prognostic index (PI). In mesothelioma, current treatments yield disappointingly poor results and there is a need to investigate new regimens. The purpose of this report is to provide a PI for PFS in mesothelioma and reference values for the PFSR.
  
  
  METHODS
  Data on 523 patients included in 10 European Organisation for Research and Treatment of Cancer (EORTC) mesothelioma studies were analysed to identify prognostic factors using a multivariate Cox regression model. Subsequently, a PI and a nomogram for PFS were developed. The PFSRs at 3, 4, 5 and 6 months were estimated.
  
  
  RESULTS
  A performance status>0, stage IV disease and mixed or sarcomatous histological type were indicators of a poor prognosis for PFS. From the PI, based on these three variables, four risk groups were defined. The median progression-free survival ranged from 5.3 to 2.1 months in these risk categories. The PFSRs at 3 months were 70.6%, 62.4%, 54.2% and 42.1% in the four categories, respectively.
  
  
  CONCLUSIONS
  The PI allows dividing patients into homogeneous risk categories in which PFSRs can be calculated and used to design future phase II mesothelioma trials. Defining homogeneous categories of patients avoids dilution of results between groups and improves the assessment of therapeutic activity.
authors.affiliation: Epidemiology and Biostatistics Unit, Université Catholique de Louvain, Ecole de Santé Publique, 1200 Brussels, Belgium. julie.francart@uclouvain.be
authors.forename: J
authors.initials: J
authors.lastname: Francart
authors.forename: E
authors.initials: E
authors.lastname: Vaes
authors.forename: S
authors.initials: S
authors.lastname: Henrard
authors.forename: C
authors.initials: C
authors.lastname: Legrand
authors.forename: P
authors.initials: P
authors.lastname: Baas
authors.forename: R
authors.initials: R
authors.lastname: Gaafar
authors.forename: J P
authors.initials: JP
authors.lastname: van Meerbeeck
authors.forename: R
authors.initials: R
authors.lastname: Sylvester
authors.forename: A
authors.initials: A
authors.lastname: Robert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000401:mortality*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D055815:Young Adult