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 in | Pediatric blood & cancer Vol. 65; no. 7; pp. e27052 - n/a |
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Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Wiley Subscription Services, Inc
01.07.2018
Wiley |
Subjects | |
Online Access | Get full text |
ISSN | 1545-5009 1545-5017 1545-5017 |
DOI | 10.1002/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. |
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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. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 |
ISSN: | 1545-5009 1545-5017 1545-5017 |
DOI: | 10.1002/pbc.27052 |