Semiquantitative mIBG Scoring as a Prognostic Indicator in Patients with Stage 4 Neuroblastoma: A Report from the Children’s Oncology Group

Radiolabeled metaiodobenzylguanidine (mIBG) is a highly sensitive and specific marker for detecting neuroblastoma. A semiquantitative mIBG score (Curie score [CS]) was assessed for utility as a prognostic indicator for a cohort of patients with highrisk metastatic disease. Methods: mIBG scans from 280 patients with mIBG-avid, stage 4 neuroblastoma enrolled on the Children’s Oncology Group (COG) protocol A3973 were evaluated at diagnosis (n 5 280), after induction chemotherapy (n 5 237), and after an autologous stem cell transplantation (n 5 178). Individual mIBG scans were evaluated at 10 different anatomic regions, with the scoring of each site (0–3) based on the extent of disease at that anatomic region. Results: There was no correlation between CS at diagnosis and subsequent treatment outcome. Patients with a CS . 2 after induction therapy had a significantly worse event-free survival (EFS) than those with scores# 2 (3-y EFS: 15.4% 6 5.3% vs. 44.9% 6 3.9%, respectively; P , 0.001). A postinduction CS . 2 identified a cohort of patients at greater risk for an event, independent of other known neuroblastoma factors, including age, MYCN status, ploidy, mitosiskaryorrhexis index, and histologic grade. For MYCN-amplified tumors, the presence (CS . 0) versus absence (CS 5 0) of residual mIBG avidity after induction was associated with a significantly worse outcome (3-y EFS: 11.8% 6 7.8% vs. 49.6% 6 7.7%, respectively; P 5 0.003). After transplantation, patients with a CS . 0 had an EFS inferior to that of patients with a CS of 0 (3-y EFS: 28.9% 6 6.8% vs. 49.3% 6 4.9%, respectively [n 5 133]; P 5 0.009). Conclusion: Curie scoring carries prognostic significance in the management of patients with high-risk neuroblastoma. In particular, patients with CSs . 2 after induction have extremely poor outcomes and should be considered for alternative therapeutic strategies.