title: Statistical validation of the EORTC prognostic model for malignant pleural mesothelioma based on three consecutive phase II trials.
abstract: OBJECTIVE
  Malignant pleural mesothelioma (MPM) carries a poor prognosis due to chemoresistance. The European Organisation for Research and Treatment of Cancer (EORTC) prognostic model was reported to predict survival in MPM. Our retrospective analysis set out to test the validity of the model as a prognostic tool in patients treated in three phase II trials at St Bartholomew's Hospital (London, United Kingdom) between 1999 and 2003.
  
  
  METHODS
  A total of 145 patients were treated in three phase II trials; vinorelbine (VIN; 70 patients), vinorelbine/oxaliplatin (VO; 26 patients), and irinotecan/cisplatin/mitomycin C (IPM; 49 patients). Two subgroups, high-risk and low-risk, were defined by EORTC prognostic score (EPS). EPS was determined by a five-parameter model incorporating age, sex, histology, probability of diagnosis, and leukocyte count. An EPS cutoff of less than 1.27 (low risk) or more than 1.27 (high risk) was used to stratify Kaplan-Meier survival curves. Each of the EPS variables exhibited either trends or significant stratification of overall survival (OS).
  
  
  RESULTS
  Multivariate analysis confirmed leukocyte count, Eastern Cooperative Oncology Group performance status, and sarcomatous histology as independent prognostic variables. EPS stratified OS in both individual and pooled trial datasets. No association between objective tumor response and EPS classification was identified by multinomial logistic regression. EPS stratified progression-free survival for the VO and IPM cohorts, but not for VIN.
  
  
  CONCLUSIONS
  This study validates the EPS system as a robust tool for stratifying small trials into low- and high-risk subgroups. EPS should facilitate patient selection and analysis in randomized clinical trials.
authors.affiliation: Lung Cancer and Mesthelioma Unit, Department of Oncology, and the Institute of Cell and Molecular Science-Pathology, St. Bartholomew's Hospital, London, United Kingdom. d.a.fennell@qmul.ac.uk
authors.forename: Dean A
authors.initials: DA
authors.lastname: Fennell
authors.forename: Amit
authors.initials: A
authors.lastname: Parmar
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shamash
authors.forename: Marie T
authors.initials: MT
authors.lastname: Evans
authors.forename: Michael T
authors.initials: MT
authors.lastname: Sheaff
authors.forename: Richard
authors.initials: R
authors.lastname: Sylvester
authors.forename: Kevin
authors.initials: K
authors.lastname: Dhaliwal
authors.forename: Nicole
authors.initials: N
authors.lastname: Gower
authors.forename: Jeremy
authors.initials: J
authors.lastname: Steele
authors.forename: Robin
authors.initials: R
authors.lastname: Rudd
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002945:Cisplatin / Q000008:administration & dosage; D017322:Clinical Trials, Phase II as Topic; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077146:Irinotecan; D016015:Logistic Models; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000401:mortality*; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D008962:Models, Theoretical; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000401:mortality*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016685:Mitomycin; D014747:Vinblastine; D000077146:Irinotecan; D002945:Cisplatin; D000077235:Vinorelbine; D002166:Camptothecin