title: Gene expression-based model using formalin-fixed paraffin-embedded biopsies predicts overall survival in advanced-stage classical Hodgkin lymphoma.
abstract: OBJECTIVE
  Our aim was to reliably identify patients with advanced-stage classical Hodgkin lymphoma (cHL) at increased risk of death by developing a robust predictor of overall survival (OS) using gene expression measured in routinely available formalin-fixed paraffin-embedded tissue (FFPET).
  
  
  METHODS
  Expression levels of 259 genes, including those previously reported to be associated with outcome in cHL, were determined by digital expression profiling of pretreatment FFPET biopsies from 290 patients enrolled onto the E2496 Intergroup trial comparing doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and Stanford V regimens in locally extensive and advanced-stage cHL. A model for OS separating patients into low- and high-risk groups was produced using penalized Cox regression. The model was tested in an independent cohort of 78 patients enriched for treatment failure but otherwise similar to patients in a population-based registry of patients treated with ABVD. Weighted analysis methods generated unbiased estimates of predictor performance in the population-based registry.
  
  
  RESULTS
  A 23-gene outcome predictor was generated. The model identified a population at increased risk of death in the validation cohort. There was a 29% absolute difference in 5-year OS between the high- and low-risk groups (63% v 92%, respectively; log-rank P < .001; hazard ratio, 6.7; 95% CI, 2.6 to 17.4). The predictor was superior to the International Prognostic Score and CD68 immunohistochemistry in multivariate analyses.
  
  
  CONCLUSIONS
  A gene expression-based predictor, developed in and applicable to routinely available FFPET biopsies, identifies patients with advanced-stage cHL at increased risk of death when treated with standard-intensity up-front regimens.
authors.affiliation: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Scott
authors.forename: Fong Chun
authors.initials: FC
authors.lastname: Chan
authors.forename: Fangxin
authors.initials: F
authors.lastname: Hong
authors.forename: Sanja
authors.initials: S
authors.lastname: Rogic
authors.forename: King L
authors.initials: KL
authors.lastname: Tan
authors.forename: Barbara
authors.initials: B
authors.lastname: Meissner
authors.forename: Susana
authors.initials: S
authors.lastname: Ben-Neriah
authors.forename: Merrill
authors.initials: M
authors.lastname: Boyle
authors.forename: Robert
authors.initials: R
authors.lastname: Kridel
authors.forename: Adele
authors.initials: A
authors.lastname: Telenius
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Woolcock
authors.forename: Pedro
authors.initials: P
authors.lastname: Farinha
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
authors.forename: Ranjana H
authors.initials: RH
authors.lastname: Advani
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Horning
authors.forename: Christian
authors.initials: C
authors.lastname: Steidl
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D020869:Gene Expression Profiling / Q000379:methods*; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D016612:Paraffin Embedding; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods*; D055815:Young Adult
chemical_list: D005404:Fixatives; D005557:Formaldehyde