title: Plasma Biomarker Enrichment of Clinical Prognostic Indices in Malignant Pleural Mesothelioma.
abstract: Prognostic models for malignant pleural mesothelioma (MPM) are needed to prevent potentially futile outcomes. We combined MPM plasma biomarkers with validated clinical prognostic indices to determine whether stratification of risk for death in 194 patients with MPM improved.
  
  
  
  Individuals were recruited from three different centers: a discovery cohort (83 patients with MPM) created by combining patients from two U.S. centers and a separate, independent cohort from Canada (111 patients with MPM). Univariable and multivariable analyses were performed on the initial discovery and independent cohorts separately. In the multivariable analyses, prognostic factors were adjusted for the European Organisation for Research and Treatment of Cancer (EORTC) prognostic index (PI) of mesothelioma. The prognostic significance of adding plasma biomarker data to the PI was determined by using the likelihood ratio test, comparing models with and without the addition of biomarker to the clinical PI. The predictive ability of the biomarker was then assessed formally using Harrell's C-index by applying the fitted model variables of the discovery cohort to the second, independent cohort, including and not including the biomarker with the PI.
  
  
  
  Higher levels of osteopontin and mesothelin were individually associated with worse prognosis after adjusting for the PI. In the independent cohort, incorporating either plasma osteopontin or mesothelin into the baseline predictive PI model substantively and statistically significantly improved Harrell's C-statistic. In the final prognostic model, log-osteopontin, EORTC clinical prognostic index, and hemoglobin remained as independently significant predictors and the entire prognostic model improved the optimism-corrected Harrell's C-index significantly, from 0.718 (0.67-0.77) to 0.801 (0.77-0.84).
  
  
  
  These data suggest a possible role for preoperative plasma biomarkers to improve the prognostic capability of the EORTC PI of MPM.
authors.affiliation: Langone Medical Center, New York University, New York, New York. Electronic address: harvey.pass@med.nyu.edu.
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Pass
authors.affiliation: Langone Medical Center, New York University, New York, New York.
authors.forename: Chandra
authors.initials: C
authors.lastname: Goparaju
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Espin-Garcia
authors.affiliation: Langone Medical Center, New York University, New York, New York.
authors.forename: Jessica
authors.initials: J
authors.lastname: Donington
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii.
authors.forename: Michele
authors.initials: M
authors.lastname: Carbone
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Devalben
authors.initials: D
authors.lastname: Patel
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Cho
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Shirish
authors.initials: S
authors.lastname: Gadgeel
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Wozniak
authors.affiliation: Langone Medical Center, New York University, New York, New York.
authors.forename: Abraham
authors.initials: A
authors.lastname: Chachoua
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Leighl
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: de Perrot
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Princess Margaret Cancer Centre, Ontario Cancer Institute, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology* / Q000628:therapy; D008297:Male; D008654:Mesothelioma / Q000097:blood* / Q000473:pathology* / Q000628:therapy; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000097:blood* / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers
keywords: Biomarkers; Mesothelin; Mesothelioma; Osteopontin; Prognosis