The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report.
OBJECTIVE
Because current approaches to risk classification and treatment stratification for children with neuroblastoma (NB) vary greatly throughout the world, it is difficult to directly compare risk-based clinical trials. The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification.


METHODS
The statistical and clinical significance of 13 potential prognostic factors were analyzed in a cohort of 8,800 children diagnosed with NB between 1990 and 2002 from North America and Australia (Children's Oncology Group), Europe (International Society of Pediatric Oncology Europe Neuroblastoma Group and German Pediatric Oncology and Hematology Group), and Japan. Survival tree regression analyses using event-free survival (EFS) as the primary end point were performed to test the prognostic significance of the 13 factors.


RESULTS
Stage, age, histologic category, grade of tumor differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were the most highly statistically significant and clinically relevant factors. A new staging system (INRG Staging System) based on clinical criteria and tumor imaging was developed for the INRG Classification System. The optimal age cutoff was determined to be between 15 and 19 months, and 18 months was selected for the classification system. Sixteen pretreatment groups were defined on the basis of clinical criteria and statistically significantly different EFS of the cohort stratified by the INRG criteria. Patients with 5-year EFS more than 85%, more than 75% to < or = 85%, > or = 50% to < or = 75%, or less than 50% were classified as very low risk, low risk, intermediate risk, or high risk, respectively.


CONCLUSIONS
By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies.
Cohn
Susan L
SL
Department of Pediatrics, The University of Chicago, Chicago, IL 60637, USA. scohn@peds.bsd.uchicago.edu
Pearson
Andrew D J
AD
London
Wendy B
WB
Monclair
Tom
T
Ambros
Peter F
PF
Brodeur
Garrett M
GM
Faldum
Andreas
A
Hero
Barbara
B
Iehara
Tomoko
T
Machin
David
D
Mosseri
Veronique
V
Simon
Thorsten
T
Garaventa
Alberto
A
Castel
Victoria
V
Matthay
Katherine K
KK
D000367:Age Factors; D002675:Child, Preschool; D015331:Cohort Studies; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D007223:Infant; D038801:International Classification of Diseases; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000145:classification* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D012044:Regression Analysis; D012307:Risk Factors
D005293:Ferritins; D007770:L-Lactate Dehydrogenase