Predicting Response to Chemotherapy in Patients With Newly Diagnosed High-Risk Neuroblastoma: A Report From the International Neuroblastoma Risk Group

JCO Clin Cancer Inform. 2021 Dec;5:1181-1188. doi: 10.1200/CCI.21.00103.


Purpose: Metaiodobenzylguanidine (MIBG) scans are a radionucleotide imaging modality that undergo Curie scoring to semiquantitatively assess neuroblastoma burden, which can be used as a marker of therapy response. We hypothesized that a convolutional neural network (CNN) could be developed that uses diagnostic MIBG scans to predict response to induction chemotherapy.

Methods: We analyzed MIBG scans housed in the International Neuroblastoma Risk Group Data Commons from patients enrolled in the Children's Oncology Group high-risk neuroblastoma study ANBL12P1. The primary outcome was response to upfront chemotherapy, defined as a Curie score ≤ 2 after four cycles of induction chemotherapy. We derived and validated a CNN using two-dimensional whole-body MIBG scans from diagnosis and evaluated model performance using area under the receiver operating characteristic curve (AUC). We also developed a clinical classification model to predict response on the basis of age, stage, and MYCN amplification.

Results: Among 103 patients with high-risk neuroblastoma included in the final cohort, 67 (65%) were responders. Performance in predicting response to upfront chemotherapy was equivalent using the CNN and the clinical model. Class-activation heatmaps verified that the CNN used areas of disease within the MIBG scans to make predictions. Furthermore, integrating predictions using a geometric mean approach improved detection of responders to upfront chemotherapy (geometric mean AUC 0.73 v CNN AUC 0.63, P < .05; v clinical model AUC 0.65, P < .05).

Conclusion: We demonstrate feasibility in using machine learning of diagnostic MIBG scans to predict response to induction chemotherapy for patients with high-risk neuroblastoma. We highlight improvements when clinical risk factors are also integrated, laying the foundation for using a multimodal approach to guiding treatment decisions for patients with high-risk neuroblastoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Iodobenzylguanidine* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Humans
  • Neuroblastoma* / diagnostic imaging
  • Neuroblastoma* / drug therapy
  • Radionuclide Imaging
  • Research Report


  • 3-Iodobenzylguanidine