title: Clinical and biologic features predictive of survival after relapse of neuroblastoma: a report from the International Neuroblastoma Risk Group project.
abstract: OBJECTIVE
  Survival after neuroblastoma relapse is poor. Understanding the relationship between clinical and biologic features and outcome after relapse may help in selection of optimal therapy. Our aim was to determine which factors were significantly predictive of postrelapse overall survival (OS) in patients with recurrent neuroblastoma--particularly whether time from diagnosis to first relapse (TTFR) was a significant predictor of OS.
  
  
  METHODS
  Patients with first relapse/progression were identified in the International Neuroblastoma Risk Group (INRG) database. Time from study enrollment until first event and OS time starting from first event were calculated. Cox regression models were used to calculate the hazard ratio of increased death risk and perform survival tree regression. TTFR was tested in a multivariable Cox model with other factors.
  
  
  RESULTS
  In the INRG database (N = 8,800), 2,266 patients experienced first progression/relapse. Median time to relapse was 13.2 months (range, 1 day to 11.4 years). Five-year OS from time of first event was 20% (SE, ± 1%). TTFR was statistically significantly associated with OS time in a nonlinear relationship; patients with TTFR of 36 months or longer had the lowest risk of death, followed by patients who relapsed in the period of 0 to less than 6 months or 18 to 36 months. Patients who relapsed between 6 and 18 months after diagnosis had the highest risk of death. TTFR, age, International Neuroblastoma Staging System stage, and MYCN copy number status were independently predictive of postrelapse OS in multivariable analysis.
  
  
  CONCLUSIONS
  Age, stage, MYCN status, and TTFR are significant prognostic factors for postrelapse survival and may help in the design of clinical trials evaluating novel agents.
authors.affiliation: Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA, USA.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Victoria
authors.initials: V
authors.lastname: Castel
authors.forename: Tom
authors.initials: T
authors.lastname: Monclair
authors.forename: Peter F
authors.initials: PF
authors.lastname: Ambros
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Ladenstein
authors.forename: Tomoko
authors.initials: T
authors.lastname: Iehara
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
mesh_terms: D000367:Age Factors; D056915:DNA Copy Number Variations; D006801:Humans; D007223:Infant; D000071447:N-Myc Proto-Oncogene Protein; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011379:Prognosis; D012008:Recurrence; D016305:Thymopentin
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D016305:Thymopentin