Corrias, MV, Parodi, S, Tchirkov, A et al. (14 more authors) (2018) 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. Pediatric Blood and Cancer, 65 (7). e27052. ISSN 1545-5009
Abstract
1 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).
2 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.
3 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.
4 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Wiley Periodicals, Inc. This is the peer reviewed version of the following article: Corrias MV, Parodi S, Tchirkov A, et al. 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. Pediatr Blood Cancer. 2018;65:e27052., which has been published in final form at https://doi.org/10.1002/pbc.27052. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | infants; neuroblastoma; outcome; RTqPCR; toddlers |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) |
Funding Information: | Funder Grant number Candlelighters Not Known Cancer Research UK A18226 |
Depositing User: | Symplectic Publications |
Date Deposited: | 19 Apr 2018 15:18 |
Last Modified: | 30 Mar 2019 01:42 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/pbc.27052 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:129816 |