title: Validation of prognostic scoring and assessment of clinical benefit for patients with bone sarcomas enrolled in phase I clinical trials.
abstract: BACKGROUND
  We sought to validate the Royal Marsden Hospital (RMH) and MD Anderson Cancer Center (MDACC) prognostic scoring systems for the selection of bone sarcoma patients for phase I clinical trials and to identify additional risk factors related to survival.
  
  
  METHODS
  We retrospectively reviewed the baseline characteristics and outcomes of 92 bone sarcoma patients who were referred to MDACC's Phase I Clinical Trials Program.
  
  
  RESULTS
  Ninety-two patients with Ewing sarcoma (N = 47), osteosarcoma (N = 22), chondrosarcoma (N = 16), and other tumors (N = 7) were evaluated; 78 were enrolled in at least 1 of 43 different phase I trials. The median overall survival (OS) was 8.8 months (95% confidence interval [CI] = 6.8-13.7 months). Independent factors that predicted shorter survival were male sex, >2 metastatic sites, >3 previous therapies, hemoglobin level <10.5 g/dL, platelet count >200 x103/L, creatinine level ≥1.3 mg/dL, and lactate dehydrogenase level >ULN. Patients with good RMH scores (0-1) had longer OS than patients with poor RMH scores (2-3) (HR = 5.8, 95% CI = 2.9-11.0; P < 0.0001), as did patients with low MDACC scores (0-1) as compared to patients with higher MDACC scores (2-4) (HR = 3.2, 95% CI = 1.9-5.6; P < 0.0001).
  
  
  CONCLUSIONS
  The RMH prognostic score can be used to predict the OS of bone cancer patients referred for phase I trials. The MDACC score added no value to the RMH score and therefore does not have a role in assessment of patients with bone tumors. Patients with advanced bone sarcomas should be considered for phase I trials.
authors.affiliation: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Livingston
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Shreyaskumar
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Benjamin
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Ludwig
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Conley
authors.affiliation: Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Herzog
authors.affiliation: Pediatric Hematology Oncology, The Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Pete
authors.initials: P
authors.lastname: Anderson
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.affiliation: Experimental Therapeutics Program, University of California - San Diego, San Diego, California, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002648:Child; D002813:Chondrosarcoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000066491:Clinical Decision-Making; D017321:Clinical Trials, Phase I as Topic; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018579:Patient Selection; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012512:Sarcoma, Ewing / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
keywords: Ewing sarcoma; bone sarcoma; osteosarcoma; phase 1 trials; prognosis scores