Changes over three decades in outcome and the prognostic influence of age-at-diagnosis in young patients with neuroblastoma: a report from the International Neuroblastoma Risk Group Project.
OBJECTIVE
Increasing age has been an adverse risk factor in children with neuroblastoma (NB) since the 1970's, with a 12-month age-at-diagnosis cut-off for treatment stratification. Over the last 30 years, treatment intensity for children >12 months with advanced-stage disease has increased; to investigate if this strategy has improved outcome and/or reduced the prognostic influence of age, we analysed the International Neuroblastoma Risk Group (INRG) database.


METHODS
Data from 11,037 children with NB (1974-2002) from Australia, Europe, Japan, North America. Cox modelling of event-free survival (EFS) tested if the era and prognostic significance of age-of-diagnosis, adjusted for bone marrow (BM) metastases and MYCN status, effects on outcome had changed.


RESULTS
Outcome improved over time: 3-year EFS 46% (1974-1989) and 71% (1997-2002). The risk for those >18 months against ≤12 decreased: hazard ratio (HR); 4.61 and 3.94. For age 13-18 months, EFS increased from 42% to 77%. Outcome was worse if: >18 months (HR 4.47); BM metastases (HR 4.00); and MYCN amplified (HR 3.97). For 1997-2002, the EFS for >18 months with BM involvement and MYCN amplification was 18%, but 89% for 0-12 months with neither BM involvement nor MYCN amplification.


CONCLUSIONS
There is clear evidence for improving outcomes for children with NB over calendar time. The adverse influence of increasing age-at-diagnosis has declined but it remains a powerful indicator of unfavourable prognosis. These results support the age-of-diagnosis cut-off of greater than 18 months as a risk criterion in the INRG classification system.
Children's Cancer and Leukaemia Group Data Centre, University of Leicester, Leicester, UK.
Veronica
V
Moroz
David
D
Machin
Andreas
A
Faldum
Barbara
B
Hero
Tomoko
T
Iehara
Veronique
V
Mosseri
Ruth
R
Ladenstein
Bruno
B
De Bernardi
Hervé
H
Rubie
Frank
F
Berthold
Katherine K
KK
Matthay
Tom
T
Monclair
Peter F
PF
Ambros
Andrew D J
AD
Pearson
Susan L
SL
Cohn
Wendy B
WB
London
D000293:Adolescent; D017677:Age Distribution; D017668:Age of Onset; D001315:Australia / Q000453:epidemiology; D019046:Bone Marrow Neoplasms / Q000401:mortality / Q000556:secondary*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005060:Europe / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D009447:Neuroblastoma / Q000401:mortality* / Q000556:secondary / Q000628:therapy; D009656:North America / Q000453:epidemiology; D011379:Prognosis; D012307:Risk Factors