title: Criteria for optimizing prognostic risk groups in pediatric cancer: analysis of data from the Children's Oncology Group.
abstract: OBJECTIVE
  Physicians who treat cancer often attempt to identify patient subgroups that are homogeneous in their chance of recurrence or death as a way to target the more toxic and presumably more effective treatments to patients with the worst prognosis. However, to date, prognosis-based treatment assignment in pediatric cancer has not been based on a quantitative assessment of the risks and benefits of different treatment strategies or on morbidity and efficacy outcome measures that are relevant to children.
  
  
  METHODS
  We performed a quantitative analysis of the risks and benefits of prognosis-based treatment assignment in two examples from the Children's Oncology Group using a mathematical model of cancer cure and permanent treatment morbidity and defined an optimality criterion for assigning treatments to specific risk groups.
  
  
  RESULTS
  In stage 4 MYCN-unamplified neuroblastoma, age-based risk grouping distinguishes clearly between patients with high and low risk of recurrence. However, our analysis suggests that the optimal age cut point depends profoundly on the morbidity of the treatments being considered and agrees with current published recommendations only for treatments that add significant morbidity. In Hodgkin's lymphoma, under our model, no clearly optimal risk groupings exist, and a compelling quantitative rationale for defining risks group at all may not exist.
  
  
  CONCLUSIONS
  Our analysis illustrates the inadequacy of naïve application of statistical criteria for defining prognostic risk groups in pediatric cancer and highlights the importance of quantifying treatment morbidity when defining risk groups or when deciding whether risk grouping is warranted.
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA 90027-6016, USA. rsposto@chla.usc.edu
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D011336:Probability; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States