Originally published as JCO Early Release 10.1200/JCO.2005.05.571 on August 22 2005

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Evidence for an Age Cutoff Greater Than 365 Days for Neuroblastoma Risk Group Stratification in the Children's Oncology Group

From the University of Florida and Children's Oncology Group Department of Statistics, Gainesville, FL; University of Alabama at Birmingham, The Children's Hospital, Birmingham, AL; University of California at San Francisco School of Medicine, San Francisco; Children's Hospital of Los Angeles and The University of Southern California Keck School of Medicine, Los Angeles, CA; Harvard University, The Dana-Farber Cancer Institute, Boston, MA; Hospital for Sick Children, Toronto, Ontario, Canada; Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA; Northwestern University's Feinberg School of Medicine, Chicago, IL

Address reprint requests to Wendy B. London, PhD, Department of Statistics, University of Florida, 104 N Main St, #600, Gainsville, FL 32601; e-mail: wendy{at}cog.ufl.edu

PURPOSE: In the Children's Oncology Group, risk group assignment for neuroblastoma is critical for therapeutic decisions, and patients are stratified by International Neuroblastoma Staging System stage, MYCN status, ploidy, Shimada histopathology, and diagnosis age. Age less than 365 days has been associated with favorable outcome, but recent studies suggest that older age cutoff may improve prognostic precision.

METHODS: To identify the optimal age cutoff, we retrospectively analyzed data from the Pediatric Oncology Group biology study 9047 and Children's Cancer Group studies 321p1-p4, 3881, 3891, and B973 on 3,666 patients (1986 to 2001) with documented ages and follow-up data. Twenty-seven separate analyses, one for each different age cutoff (adjusting for MYCN and stage), tested age influence on outcome. The cutoff that maximized outcome difference between younger and older patients was selected.

RESULTS: Thirty-seven percent of patients were younger than 365 days, and 64% were 365 days old (4-year event-free survival [EFS] rate ± SE: 83% ± 1% [n = 1,339] and 45% ± 1% [n = 2,327], respectively; P < .0001). Graphical analyses revealed the continuous nature of the prognostic contribution of age to outcome. The optimal 460-day cutoff we selected maximized the outcome difference between younger and older patients. Forty-three percent were younger than 460 days, and 57% were 460 days old (4-year EFS rate ± SE: 82% ± 1% [n = 1,589] and 42% ± 1% [n = 2,077], respectively; P < .0001). Using a 460-day cutoff (assuming stage 4, MYCN-amplified patients remain high-risk), 5% of patients (365 to 460 days: 4-year EFS 92% ± 3%; n = 135) fell into a lower risk group.

CONCLUSION: The prognostic contribution of age to outcome is continuous in nature. Within clinically relevant risk stratification, statistical support exists for an age cutoff of 460 days.

Supported in part by Pediatric Oncology Group Statistics and Data Center grant U10 CA29139, Children's Cancer Group Statistics and Data Center grant U10 CA13539, and Children's Oncology Group Statistics and Data Center grant U10 CA98413-01.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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