Event‐free survival of infants and toddlers enrolled in the HR‐NBL‐1/SIOPEN trial is associated with the level of neuroblastoma mRNAs at diagnosis

Background The purpose of this study was to evaluate whether levels of neuroblastoma mRNAs in bone marrow and peripheral blood from stage M infants (≤12 months of age at diagnosis, MYCN amplified) and toddlers (between 12 and 18 months, any MYCN status) predict event‐free survival (EFS). Methods Bon...

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Published inPediatric blood & cancer Vol. 65; no. 7; pp. e27052 - n/a
Main Authors Corrias, Maria V., Parodi, Stefano, Tchirkov, Andrei, Lammens, Tim, Vicha, Ales, Pasqualini, Claudia, Träger, Catarina, Yáñez, Yania, Dallorso, Sandro, Varesio, Luigi, Luksch, Roberto, Laureys, Genevieve, Valteau‐Couanet, Dominique, Canete, Adela, Pöetschger, Ulrike, Ladenstein, Ruth, Burchill, Susan A.
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.07.2018
Wiley
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Online AccessGet full text
ISSN1545-5009
1545-5017
1545-5017
DOI10.1002/pbc.27052

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Summary:Background The purpose of this study was to evaluate whether levels of neuroblastoma mRNAs in bone marrow and peripheral blood from stage M infants (≤12 months of age at diagnosis, MYCN amplified) and toddlers (between 12 and 18 months, any MYCN status) predict event‐free survival (EFS). Methods Bone marrow aspirates and peripheral blood samples from 97 infants/toddlers enrolled in the European High‐Risk Neuroblastoma trial were collected at diagnosis in PAXgene™ blood RNA tubes. Samples were analyzed by reverse transcription quantitative polymerase chain reaction according to standardized procedures. Results Bone marrow tyrosine hydroxylase (TH) or paired‐like homeobox 2b (PHOX2B) levels in the highest tertile were associated with worse EFS; hazard ratios, adjusted for age and MYCN status, were 1.5 and 1.8 respectively. Expression of both TH and PHOX2B in the highest tertile predicted worse outcome (p = 0.015), and identified 20 (23%) infants/toddlers with 5‐year EFS of 20% (95%CI: 4%–44%). Prognostic significance was maintained after adjusting for over‐fitting bias (p = 0.038), age and MYCN status. In peripheral blood, PHOX2B levels in the highest tertile predicted a two‐fold increased risk of an event (p = 0.032), and identified 23 (34%) infants/toddlers with 5‐year EFS of 29% (95%CI: 12%–48%). Time‐dependent receiver operating characteristic analysis confirmed the prognostic value of combined TH and PHOX2B in bone marrow and of PHOX2B in peripheral blood during the first year of follow‐up. Conclusions High levels of bone marrow TH and PHOX2B and of peripheral blood PHOX2B at diagnosis allow early identification of a group of high‐risk infant and toddlers with neuroblastoma who may be candidates for alternative treatments. Integration with additional biomarkers, as well as validation in additional international trials is warranted.
Bibliography:Maria V. Corrias, Andrei Tchirkov, Tim Lammens, Ales Vicha, Claudia Pasqualini, Catarina Träger, Yania Yáñez, Sandro Dallorso, Luigi Varesio, and Susan A. Burchill are members of the SIOPEN Molecular Monitoring Group.
Grant sponsor: Neuroblastoma UK, University of Leeds, Fondazione Italiana per la Lotta al Neuroblastoma, French National Hospital research project, Association Les Bagouz’à Manon, vzw Kinderkankerfonds, Onderzoeksproject gerealiseerd met de steun van Kom op tegen Kanker, Asociacion Pablo Ugarte
Dr. Luigi Varesio prematurely passed away last December. The colleagues that had the privilege to collaborate with him dedicate this manuscript to his memory.
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ISSN:1545-5009
1545-5017
1545-5017
DOI:10.1002/pbc.27052