Ref ID: 336.1

Evidence for an age cut-off higher than 365 days for neuroblastoma risk group stratification in the Children’s Oncology Group (COG)

Wendy B London1, Robert P Castleberry2, Thomas A Look3, Paul Thorner4, Garrett M Brodeur5, John M
Maris5, Susan L Cohn6

Children's Oncology Group Department of Statistics1, University of Florida, Gainesville, FL; University of Alabama at Birmingham2, The Children's Hospital; Harvard University3, The Dana-Farber Cancer Institute; Hospital for Sick Children4, Toronto, ON; Department of Oncology5, Children's Hospital of Philadelphia and University of Pennsylvania, PA; Department of Pediatrics6, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.

In COG, risk group and therapy for neuroblastoma patients is currently stratified based on the factors stage, MYCN, ploidy, Shimada histology and age at diagnosis with a cutoff of 365 days. Patients <365d,
depending on risk factors, tend to be assigned to lower risk and receive less therapy than patients >365d. The excellent long-term outcome of a subset of patients 1-2yrs of age suggests increasing the age cutoff, but how far? A more accurate determination of a data-driven prognostic and biologically rational age cutoff is ongoing.  To date, retrospective analysis of POG biology study 9047 was performed in 1660 patients (1990-1999) with sufficient data.  The median age was 483d, with 11% of patients >5 years.  42% of patients were <365d, 58% were >365d of age, with 4year EFS rates + SE of 85%+2% (n=703) and 51%+2% (n=957), respectively (p<0.0001).  Multivariate analysis revealed an age cutoff of 365d (p<0.0001) to be independent prognostic factor after adjustment for MYCN (p<0.0001) and stage (p<0.0001).  Adjusting for MYCN and stage, plots of relative risk versus age cutoff were used to visualize the continuous nature of the prognostic contribution of age.  From a data-driven standpoint, age cutoff of 510d was chosen to maximize relative risk between the two age groups, and 149 patients (4year EFS: 80%+4%) were switched to lower risk group. 51% of patients were <510d, 49% were >510d of age, with 4year EFS rates + SE of 84%+2% (n=852) and 46%+2% (n=808), respectively (p<0.0001). In selecting a definitive new age cutoff, comparison will be made to analogous analyses of more homogenously treated patients from the Children's Cancer Group, and consideration given to the risk/benefit of future treatment scenarios. 

Presentation mode(s): oral-presentation – pc-projector