Response- and Biology-Based Therapy for Pediatric Intermediate-Risk Neuroblastoma


Key Points

  • Use of reduced therapy in subsets of patients did not adversely affect overall survival.
  • Improved treatment strategies are needed for infants with unfavorable biology stage IV disease.

As reported in the Journal of Clinical Oncology by Twist et al, use of reduced therapy for subsets of pediatric patients with intermediate-risk neuroblastoma in the Children’s Oncology Group (COG) study ANBL0531 did not affect the excellent overall survival rates observed in prior COG studies in this setting.

As stated by the investigators, “The primary objective of [this trial] was to reduce therapy for subsets of patients with intermediate-risk neuroblastoma using a biology- and response-based algorithm to assign treatment duration while maintaining a 3-year overall survival … of 95% or more for the entire cohort.”

Study Details

Patients eligible for enrollment in the study were younger than 12 years with intermediate-risk stage IIA/IIB or stage III tumors with favorable histology; infants younger than 365 days with stage III, IV, or IVS disease; and toddlers aged 365 days to younger than 547 days with favorable histology, hyperdiploid stage IV, or unfavorable histology stage III tumors. Patients with MYCN-amplified tumors were not eligible.

A total of 464 patients were enrolled between October 2007 and June 2011. Patients were assigned to initially receive two (group 2; n = 175), four (group 3; n = 141), or eight (group 4; n = 88) cycles of chemotherapy with or without surgery on the basis of prognostic markers consisting of age at diagnosis, disease stage, histology, and genetic features of the tumor, including allelic status of chromosomes 1p and 11q. The number of cycles represented a reduction in therapy in subsets of patients compared with treatment of patients in legacy COG studies used as historic controls. The actual duration of therapy in the current study was determined by overall response.

Treatment Reduction and Survival Outcomes

Overall, 97 patients in group 2 (55.4%), 31 patients in group 3 (22.0%), and 16 patients in group 4 (18.2%) received fewer cycles of chemotherapy vs legacy COG studies. Among the 83 patients with stage IIA/IIB or stage III disease who received additional cycles of chemotherapy, 8 had ganglioneuroblastoma, 7 had neuroblastoma-differentiating subtype, and 2 had ganglioneuroma-maturing subtype; 42 patients had paraspinal/intraspinal tumors.

In the entire cohort, 3-year event-free survival and overall survival rates were 83.2% (95% confidence interval [CI] = 79.4%–87.0%) and 94.9% (95% CI = 92.7%–97.2%). Compared with infants with stage IV tumors with ≥ 1 unfavorable biologic feature (n = 47), those with favorable biology (n = 61) had improved 3-year event-free survival (86.9% vs 66.8%, P = .02) and a trend toward improved 3-year overall survival (95.0% vs 86.7%, P = .08). Among patients with localized disease, 3-year overall survival was 100%.

The investigators concluded, “Excellent survival was achieved with this treatment algorithm, with reduction of therapy for subsets of patients. More effective treatment strategies still are needed for infants with unfavorable biology stage IV disease.”

Susan L. Cohn, MD, of the Department of Pediatrics, The University of Chicago, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute, National Clinical Trials Network Operations Center, and St Baldrick’s Foundation. For full disclosures of the study authors, visit

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