Predictors of differential response to induction therapy in high-risk neuroblastoma: A report from the Children's Oncology Group (COG)

Navin Pinto, Arlene Naranjo, Emily Hibbitts, Susan G. Kreissman, M. Meaghan Granger, Meredith S. Irwin, Rochelle Bagatell, Wendy B. London, Emily G. Greengard, Julie R. Park, Steven G. DuBois

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background: Induction chemotherapy plays an important role in the management of patients with high-risk neuroblastoma. Predictors of response to induction therapy are largely lacking. We sought to describe clinical and biological features associated with induction response. Methods: Patients from four consecutive COG high-risk trials were included. Response was evaluated by the 1993 International Neuroblastoma Response Criteria. The primary end-point was end-induction partial response (PR) or better. Univariate analyses were performed to compare response as a function of clinical or biologic predictors. A multivariate logistic regression model using significant predictors from univariate analyses was constructed to model PR or better. Results: The analytic cohort included 1242 patients. End-induction response ≥PR was significantly associated with higher event-free and overall survival. Baseline factors associated with ≥PR included age <18 months (87.4% with ≥PR vs. 78.7% if older; p = 0.0103), International Neuroblastoma Staging System non-stage 4 (89.0% vs. 78.4% if stage 4; p = 0.0016), MYCN amplification (85.5% vs. 77.1% if non-amplified; p = 0.0006), 1p loss of heterozygosity (LOH; 85.6% vs. 76.0% if no LOH; p = 0.0085), no 11q LOH (84.8% vs. 70.9% if 11q LOH; p = 0.0004) and high mitosis-karyorrhexis index (MKI; 84.5% vs. 77.5% if low-intermediate MKI; p = 0.0098). On multivariable analysis (n = 407), the absence of 11q LOH was the only factor that remained significantly associated with ≥PR (odds ratio: 1.962 vs. 11q LOH; 95% confidence interval 1.104–3.487; p = 0.0216). Conclusions: Improved end-induction response in high-risk neuroblastoma is associated with longer survival. Patients with 11q LOH are less likely to respond to induction therapies and should be prioritised for novel approaches in future trials.

Original languageEnglish (US)
Pages (from-to)66-79
Number of pages14
JournalEuropean Journal of Cancer
Volume112
DOIs
StatePublished - May 2019

Bibliographical note

Funding Information:
National Institutes of Health ( U10 CA180899 ) (Children's Oncology Group Statistics & Data Center grant), NCTN Operations Center Grant U10 CA180886 , and St. Baldrick's Foundation .

Publisher Copyright:
© 2019 Elsevier Ltd

Keywords

  • Biomarkers
  • Neuroblastoma
  • Paediatric oncology

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