Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study.
Details
Serval ID
serval:BIB_9982CD87F060
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study.
Journal
Pediatric blood & cancer
ISSN
1545-5017 (Electronic)
ISSN-L
1545-5009
Publication state
Published
Issued date
11/2018
Peer-reviewed
Oui
Volume
65
Number
11
Pages
e27363
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Risk stratification is crucial to treatment decision-making in neuroblastoma. This study aimed to explore factors present at diagnosis affecting outcome in patients aged ≥18 months with metastatic neuroblastoma and to develop a simple risk score for prognostication.
Data were derived from the European high-risk neuroblastoma 1 (HR-NBL1)/International Society for Paediatric Oncology European Neuroblastoma (SIOPEN) trial with analysis restricted to patients aged ≥18 months with metastatic disease and treated prior to the introduction of immunotherapy. Primary endpoint was 5-year event-free survival (EFS). Prognostic factors assessed were sex, age, tumour MYCN amplification (MNA) status, serum lactate dehydrogenase (LDH)/ferritin, primary tumour and metastatic sites. Factors significant in univariate analysis were incorporated into a multi-variable model and an additive scoring system developed based on estimated log-cumulative hazard ratios.
The cohort included 1053 patients with median follow-up 5.5 years and EFS 27 ± 1%. In univariate analyses, age; serum LDH and ferritin; involvement of bone marrow, bone, liver or lung; and >1 metastatic system/compartment were associated with worse EFS. Tumour MNA was not associated with worse EFS. A multi-variable model and risk score incorporating age (>5 years, 2 points), serum LDH (>1250 U/L, 1 point) and number of metastatic systems (>1, 2 points) were developed. EFS was significantly correlated with risk score: EFS 52 ± 9% for score = 0 versus 6 ± 3% for score = 5 (P < 0.0001).
A simple score can identify an "ultra-high risk" (UHR) cohort (score = 5) comprising 8% of patients with 5-year EFS <10%. These patients appear not to benefit from induction therapy and could potentially be directed earlier to alternative experimental therapies in future trials.
Data were derived from the European high-risk neuroblastoma 1 (HR-NBL1)/International Society for Paediatric Oncology European Neuroblastoma (SIOPEN) trial with analysis restricted to patients aged ≥18 months with metastatic disease and treated prior to the introduction of immunotherapy. Primary endpoint was 5-year event-free survival (EFS). Prognostic factors assessed were sex, age, tumour MYCN amplification (MNA) status, serum lactate dehydrogenase (LDH)/ferritin, primary tumour and metastatic sites. Factors significant in univariate analysis were incorporated into a multi-variable model and an additive scoring system developed based on estimated log-cumulative hazard ratios.
The cohort included 1053 patients with median follow-up 5.5 years and EFS 27 ± 1%. In univariate analyses, age; serum LDH and ferritin; involvement of bone marrow, bone, liver or lung; and >1 metastatic system/compartment were associated with worse EFS. Tumour MNA was not associated with worse EFS. A multi-variable model and risk score incorporating age (>5 years, 2 points), serum LDH (>1250 U/L, 1 point) and number of metastatic systems (>1, 2 points) were developed. EFS was significantly correlated with risk score: EFS 52 ± 9% for score = 0 versus 6 ± 3% for score = 5 (P < 0.0001).
A simple score can identify an "ultra-high risk" (UHR) cohort (score = 5) comprising 8% of patients with 5-year EFS <10%. These patients appear not to benefit from induction therapy and could potentially be directed earlier to alternative experimental therapies in future trials.
Keywords
Age Factors, Biomarkers, Tumor/analysis, Child, Child, Preschool, Clinical Trials as Topic, Disease-Free Survival, Female, Ferritins/blood, Humans, Infant, Kaplan-Meier Estimate, L-Lactate Dehydrogenase/blood, Male, N-Myc Proto-Oncogene Protein/genetics, Neuroblastoma/mortality, Neuroblastoma/pathology, Prognosis, Progression-Free Survival, Proportional Hazards Models, Risk Factors, Sex Factors, lactate dehydrogenase, metastatic, neuroblastoma, relapse, risk stratification, ultra-high risk
Pubmed
Web of science
Create date
31/07/2018 15:52
Last modification date
20/08/2019 16:01