Survival in Patients With Neuroblastoma on Reduced Therapy as a Result of Change in COG Risk Stratification

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In an analysis recently reported in the Journal of Clinical Oncology,1 Bender et al found that “excellent” survival outcomes were achieved in patients receiving reduced treatment for neuroblastoma as a result of reassignment to intermediate risk from high risk based on a change in the minimum age for high-risk disease classification in Children’s Oncology Group (COG) risk stratification.

As stated by the investigators: “In 2006, COG reclassified subgroups of toddlers diagnosed with neuroblastoma from high risk to intermediate risk when the age cutoff for high-risk assignment was raised from [age] 365 days (12 months) to 547 days (18 months). The primary aim of this retrospective study was to determine if excellent outcome was maintained after assigned reduction of therapy.”

Hannah G. Bender

Hannah G. Bender

Study Details

A total of 9,189 children (up to age 3 at diagnosis) enrolled in a COG biology study from 1990 to 2018 were eligible for the analysis.

Assigned therapy was reduced for two cohorts of interest on the basis of the change in age cutoff:

365 to 546 days old with International Neuroblastoma Staging System (INSS) stage 4, MYCN not amplified (MYCN-NA), favorable International Neuroblastoma Pathology Classification (INPC), hyperdiploid tumors (the 12–18 month/stage 4/favorable biology cohort)

365 to 546 days old with INSS stage 3, MYCN-NA, and unfavorable INPC tumors (the 12–18-month/stage 3/MYCN-NA/unfavorable biology cohort).

Key Findings

In the favorable biology cohort, the 5-year event-free survival (± standard error) before 2006 (n = 40) vs 2006 and later (n = 55) assigned reduction in therapy was similar: 89% ± 5.1% vs 87% ± 4.6% (P = .7). Findings were similar for the 5-year overall survival: 89% ± 5.1% vs 94% ± 3.2% (P = .4).

In the unfavorable biology cohort, the 5-year event-free and overall survival were both 100%, before (n = 6) and after (n = 4) 2006.

Patients in the favorable biology cohort plus the unfavorable biology cohort classified as high risk ≤ 2006 had 5-year event-free and overall survival of 91% ± 4.4% and 91% ± 4.5% vs 38% ± 1.3% (P < .0001) and 43% ± 1.3% (P < .0001) for all other high-risk patients. Patients in the two cohorts classified as intermediate risk ≤ 2006 had 5-year event-free and overall survival of 88% ± 4.3% and 95% ± 2.9% vs 88% ± 0.9% (P = .87) and 95% ± 0.6% (P = .85) for all other intermediate-risk patients.

The investigators concluded: “Excellent outcome was maintained among subsets of toddlers with neuroblastoma assigned to reduced treatment after reclassification of risk group from high to intermediate on the basis of new age cutoffs. Importantly, as documented in prior trials, intermediate-risk therapy is not associated with the degree of acute toxicity and late effects commonly observed with high-risk regimens.”

Hannah G. Bender, MD candidate, of Dana-Farber is the first author. Wendy B. London, PhD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School, is the corresponding author of the Journal of Clinical Oncology article. 

DISCLOSURE: The study was supported by National Institutes of Health grants to the Children’s Oncology Group. For full disclosures of the study authors, visit


1. Bender HG, Irwin MS, Hogarty MD, et al: Survival of patients with neuroblastoma after assignment to reduced therapy because of the 12- to 18-month change in age cutoff in Children’s Oncology Group risk stratification. J Clin Oncol. April 25, 2023 (early release on line).