In an analysis reported in the Journal of Clinical Oncology, 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.”
Study Details
A total of 9,189 children aged < 3 years 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 12-18mo/Stage4/FavBiology cohort
- 365 to 546 days old with INSS stage 3, MYCN-NA, and unfavorable INPC tumors: the 12-18mo/Stage3/MYCN-NA/Unfav cohort.
Key Findings
In the 12-18mo/Stage4/FavBiology cohort, 5-year event-free survival (± standard error) before (≤ 2006; n = 40) vs after (> 2006; n = 55) assigned reduction in therapy was similar: 89% ± 5.1% vs 87% ± 4.6% (P = .7). Findings were similar for 5-year overall survival: 89% ± 5.1% vs 94% ± 3.2% (P = .4).
In the 12-18mo/Stage3/MYCN-NA/Unfav cohort, 5-year event-free and overall survival were both 100%, before (n = 6) and after (n = 4) 2006.
Patients in the 12-18mo/Stage4/FavBiology plus 12-18mo/Stage3/MYCN-NA/Unfav cohorts 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.”
Wendy B. London, PhD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School, is the corresponding author for 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 ascopubs.org.
