Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study

Daniel A Morgenstern, Ulrike Pötschger, Lucas Moreno, Vassilios Papadakis, Cormac Owens, Shifra Ash, Claudia Pasqualini, Roberto Luksch, Alberto Garaventa, Adela Canete, Martin Elliot, Aleksandra Wieczorek, Geneviève Laureys, Per Kogner, Josef Malis, Ellen Ruud, Maja Beck-Popovic, Gudrun Schleiermacher, Dominique Valteau-Couanet, Ruth Ladenstein

Research output: Contribution to journalArticle

Abstract

BACKGROUND: 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.

PROCEDURE: 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.

RESULTS: 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).

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)e27363
JournalPediatric Blood and Cancer
Volume65
Issue number11
DOIs
Publication statusPublished - Nov 2018

Fingerprint

Neuroblastoma
Disease-Free Survival
L-Lactate Dehydrogenase
Ferritins
Serum
Neoplasms
Investigational Therapies
Complementary Therapies
Immunotherapy
Decision Making
Bone Marrow
Pediatrics
Bone and Bones
Lung
Liver
Therapeutics

Cite this

Morgenstern, D. A., Pötschger, U., Moreno, L., Papadakis, V., Owens, C., Ash, S., ... Ladenstein, R. (2018). Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study. Pediatric Blood and Cancer, 65(11), e27363. https://doi.org/10.1002/pbc.27363

Risk stratification of high-risk metastatic neuroblastoma : A report from the HR-NBL-1/SIOPEN study. / Morgenstern, Daniel A; Pötschger, Ulrike; Moreno, Lucas; Papadakis, Vassilios; Owens, Cormac; Ash, Shifra; Pasqualini, Claudia; Luksch, Roberto; Garaventa, Alberto; Canete, Adela; Elliot, Martin; Wieczorek, Aleksandra; Laureys, Geneviève; Kogner, Per; Malis, Josef; Ruud, Ellen; Beck-Popovic, Maja; Schleiermacher, Gudrun; Valteau-Couanet, Dominique; Ladenstein, Ruth.

In: Pediatric Blood and Cancer, Vol. 65, No. 11, 11.2018, p. e27363.

Research output: Contribution to journalArticle

Morgenstern, DA, Pötschger, U, Moreno, L, Papadakis, V, Owens, C, Ash, S, Pasqualini, C, Luksch, R, Garaventa, A, Canete, A, Elliot, M, Wieczorek, A, Laureys, G, Kogner, P, Malis, J, Ruud, E, Beck-Popovic, M, Schleiermacher, G, Valteau-Couanet, D & Ladenstein, R 2018, 'Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study', Pediatric Blood and Cancer, vol. 65, no. 11, pp. e27363. https://doi.org/10.1002/pbc.27363
Morgenstern, Daniel A ; Pötschger, Ulrike ; Moreno, Lucas ; Papadakis, Vassilios ; Owens, Cormac ; Ash, Shifra ; Pasqualini, Claudia ; Luksch, Roberto ; Garaventa, Alberto ; Canete, Adela ; Elliot, Martin ; Wieczorek, Aleksandra ; Laureys, Geneviève ; Kogner, Per ; Malis, Josef ; Ruud, Ellen ; Beck-Popovic, Maja ; Schleiermacher, Gudrun ; Valteau-Couanet, Dominique ; Ladenstein, Ruth. / Risk stratification of high-risk metastatic neuroblastoma : A report from the HR-NBL-1/SIOPEN study. In: Pediatric Blood and Cancer. 2018 ; Vol. 65, No. 11. pp. e27363.
@article{abca092960ff490f94de012f26f4d52d,
title = "Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study",
abstract = "BACKGROUND: 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.PROCEDURE: 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.RESULTS: 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).CONCLUSIONS: 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.",
author = "Morgenstern, {Daniel A} and Ulrike P{\"o}tschger and Lucas Moreno and Vassilios Papadakis and Cormac Owens and Shifra Ash and Claudia Pasqualini and Roberto Luksch and Alberto Garaventa and Adela Canete and Martin Elliot and Aleksandra Wieczorek and Genevi{\`e}ve Laureys and Per Kogner and Josef Malis and Ellen Ruud and Maja Beck-Popovic and Gudrun Schleiermacher and Dominique Valteau-Couanet and Ruth Ladenstein",
note = "{\circledC} 2018 Wiley Periodicals, Inc.",
year = "2018",
month = "11",
doi = "10.1002/pbc.27363",
language = "English",
volume = "65",
pages = "e27363",
journal = "Pediatric Blood and Cancer",
issn = "1545-5009",
publisher = "John Wiley and Sons Inc.",
number = "11",

}

TY - JOUR

T1 - Risk stratification of high-risk metastatic neuroblastoma

T2 - A report from the HR-NBL-1/SIOPEN study

AU - Morgenstern, Daniel A

AU - Pötschger, Ulrike

AU - Moreno, Lucas

AU - Papadakis, Vassilios

AU - Owens, Cormac

AU - Ash, Shifra

AU - Pasqualini, Claudia

AU - Luksch, Roberto

AU - Garaventa, Alberto

AU - Canete, Adela

AU - Elliot, Martin

AU - Wieczorek, Aleksandra

AU - Laureys, Geneviève

AU - Kogner, Per

AU - Malis, Josef

AU - Ruud, Ellen

AU - Beck-Popovic, Maja

AU - Schleiermacher, Gudrun

AU - Valteau-Couanet, Dominique

AU - Ladenstein, Ruth

N1 - © 2018 Wiley Periodicals, Inc.

PY - 2018/11

Y1 - 2018/11

N2 - BACKGROUND: 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.PROCEDURE: 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.RESULTS: 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).CONCLUSIONS: 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.

AB - BACKGROUND: 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.PROCEDURE: 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.RESULTS: 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).CONCLUSIONS: 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.

U2 - 10.1002/pbc.27363

DO - 10.1002/pbc.27363

M3 - Article

C2 - 30015396

VL - 65

SP - e27363

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

SN - 1545-5009

IS - 11

ER -