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.