Impact of diagnostic and end-of-induction Curie scores with tandem high-dose chemotherapy and autologous transplants for metastatic high-risk neuroblastoma: A report from the Children's Oncology Group.

Abstract

Diagnostic mIBG (meta-iodobenzylguanidine) scans are an integral component of response assessment in children with high-risk neuroblastoma. The role of end-of-induction (EOI) Curie scores (CS) was previously described in patients undergoing a single course of high-dose chemotherapy (HDC) and autologous hematopoietic cell transplant (AHCT) as consolidation therapy. We now examine the prognostic significance of CS in patients randomized to tandem HDC and AHCT on the Children's Oncology Group (COG) trial ANBL0532. A retrospective analysis of mIBG scans obtained from patients enrolled in COG ANBL0532 was performed. Evaluable patients had mIBG-avid, International Neuroblastoma Staging System (INSS) stage 4 disease, did not progress during induction therapy, consented to consolidation randomization, and received either single or tandem HDC (n=80). Optimal CS cut points maximized the outcome difference (≤CS vs. >CS cut-off) according to the Youden index. For recipients of tandem HDC, the optimal cut point at diagnosis was CS=12, with superior event-free survival (EFS) from study enrollment for patients with CS≤12 (3-year EFS 74.2% ± 7.9%) versus CS>12 (59.2% ± 7.1%) (p=.002). At EOI, the optimal cut point was CS=0, with superior EOI EFS for patients with CS=0 (72.9% ± 6.4%) versus CS>0 (46.5% ± 9.1%) (p=.002). In the setting of tandem transplantation for children with high-risk neuroblastoma, CS at diagnosis and EOI may identify a more favorable patient group. Patients treated with tandem HDC who exhibited a CS≤12 at diagnosis or CS=0 at EOI had superior EFS compared to those with CS above these cut points.