INTRODUCTION
Outcomes for children with high-risk neuroblastoma have improved over the past two decades with the addition of immunotherapy and tandem autologous hematopoietic cell transplantation (AHCT).1-3 Park et al demonstrated a significant improvement in survival for patients treated with tandem AHCT vs single AHCT on the Children’s Oncology Group (COG) trial ANBL0532, “A Phase III Randomized Trial of Single versus Tandem Myeloablative Consolidation Therapy for High-Risk Neuroblastoma”, with 3-year EFS 61.6% vs 48.4%, respectively.3 Preparative regimens for tandem AHCT included cyclophosphamide/thiotepa and dose-reduced carboplatin/etoposide/melphalan (CEM); while single AHCT utilized CEM.3-5 Despite the current multimodal approach, approximately 10-15% of patients develop disease progression during induction therapy and another 40% relapse after an initial response to induction therapy.4,6 For patients who develop relapsed disease, specifically those who relapse 6-18 months from initial diagnosis, 5-year overall survival (OS) is less than 20%.7 The ability to identify both clinical and/or biologic prognostic markers of response earlier in a patient’s treatment course may guide subsequent treatment decision-making.
Meta-iodobenzylguanidine (mIBG) is a structural analogue of the catecholamine norepinephrine. Approximately 90% of neuroblastomas concentrate mIBG within sites of disease including marrow, cortical bone, and soft tissue.8-10 In 1995, a semiquantitative mIBG scoring system (Curie scoring; CS) was developed to describe the extent of mIBG uptake within individual patients, and serve as an imaging biomarker for outcome prediction.11 The role of Curie scoring as a prognostic indicator for high-risk neuroblastoma has been reported in several institutional and cooperative group trials, including trials within the COG and the International Society of Paediatric Oncology European Neuroblastoma (SIOPEN) Research Network.12-14 In particular, a CS>2 at the end of induction (EOI) was associated with inferior outcomes in two independent, cooperative group trials, the European high-risk neuroblastoma trial SIOPEN/HR-NBL1 and the COG high-risk neuroblastoma study COG A3973.12,13
To date, the prognostic significance of Curie scoring has been reported within the context of patients who underwent induction followed by consolidation therapy with a single AHCT, with either busulfan/melphalan or CEM given as AHCT conditioning,12,13 although few patients received post-transplant anti-disialoganglioside (GD2) immunotherapy which is now considered standard of care.1,15 The aim of our current study was to investigate the prognostic significance of CS at diagnosis and at EOI for patients with newly diagnosed high-risk neuroblastoma treated with tandem AHCT on COG ANBL0532, including those who also received anti-GD2 immunotherapy.