Evaluating the Prognostic Significance of Circulating mRNAs in Children with Refractory or Relapsed Neuroblastoma (RR-NBL); a BEACON-Neuroblastoma Biomarker Study
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All Authors
Bentham, Matt
Burchill, Susan A.
Roundhill, Elizabeth
Weston, Rebekah
Laidler, Jennifer
Wheatley, Keith
Moreno, Lucas
LTHT Author
LTHT Department
Non Medic
Publication Date
2025
Item Type
Conference Abstract
Language
Subject
Subject Headings
Bitstream
Abstract
Introduction/Background
Despite therapeutic advances, high-risk neuroblastoma remains clinically challenging, with a 5-year survival below 50%. For relapsed/refractory (RR) cases, overall survival (OS) drops to <20%. Previously, we showed that detecting the adrenergic (ADR) neuroblastoma mRNAs, PHOX2B (paired-like homeobox 2B) and TH (tyrosine hydroxylase), in blood predicts prognosis (1). Given that neuroblastoma comprises both ADR and more mesenchymal-like (MES) cells, which influence progression and relapse (2,3), we analysed the expression of ADR and a panel of MES mRNAs in RR-NBL patients from the BEACON-Neuroblastoma trial (NCT02308527).
Aims
Early risk identification could improve outcomes by guiding treatment modifications. Using ADR markers we predict outcomes in 80% of high-risk patients using simple blood samples. We hypothesis that by including MES-marker expression prognostic information for the remaining 20 % of patient could be obtained.
Methods
RNA was extracted from 2ml blood samples collected in PAXgene™ tubes at trial entry (n=74) and at cycles 2 (n=42), 4 (n=31), 6 (n=24), and end of treatment (n=25) (4). Panels of ADR and MES mRNAs were quantified by RT-qPCR using TaqMan Low Density Arrays (TLDA). Euclidean clustering generated heat maps identifying ADR and MES gene signatures.
Results
Baseline detection of TH, PHOX2B, or both correlated with reduced progression-free survival (PFS) and OS, with combined detection showing stronger associations (PFS HR 2.68; OS HR 2.84). Their presence post-cycle 2 and 6 correlated with progression and poor OS. Clustering of the TLDA data revealed an ADR signature at baseline, which intensified at treatment end, supporting its role in relapse. MES mRNA profiling further stratified patients, offering potential new biomarkers of risk.
Conclusion/Implications
Blood-based detection of TH and PHOX2B at trial entry and treatment end identifies RR-NBL patients at highest risk. MES mRNAs could enhance risk stratification. This simple test could help prioritise children for alternative therapies.