Evidence map›Paper›PMID 39722049›Full record

ArticleJournal of experimental & clinical cancer research : CR2024

Sensitive liquid biopsy monitoring correlates with outcome in the prospective international GPOH-DCOG high-risk neuroblastoma RT-qPCR validation study.

Lieke M J van Zogchel, Boris Decarolis, Esther M van Wezel, Lily Zappeij-Kannegieter, Nina U Gelineau, Roswitha Schumacher-Kuckelkorn, Thorsten Simon, Frank Berthold, Max M van Noesel, Marta Fiocco and 4 more

Abstract readValidation Study
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Lieke M J van ZogchelPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0003-3557-7195
Boris DecarolisDepartment of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, and Medical Faculty, University of Cologne, Köln, Germany.
Esther M van WezelDepartment of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory of the Amsterdam UMC, Amsterdam, The Netherlands.
Lily Zappeij-KannegieterDepartment of Immunocytology, Sanquin Research and Landsteiner Laboratory of the Amsterdam UMC, Amsterdam, The Netherlands.
Nina U GelineauPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Roswitha Schumacher-KuckelkornDepartment of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, and Medical Faculty, University of Cologne, Köln, Germany.
Thorsten SimonDepartment of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, and Medical Faculty, University of Cologne, Köln, Germany.
Frank BertholdDepartment of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, and Medical Faculty, University of Cologne, Köln, Germany.
Max M van NoeselPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Marta FioccoPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
C Ellen van der SchootDepartment of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory of the Amsterdam UMC, Amsterdam, The Netherlands.
Barbara Hero *Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, and Medical Faculty, University of Cologne, Köln, Germany.
Janine Stutterheim *Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Godelieve A M Tytgat *Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. g.a.m.tytgat@prinsesmaximacentrum.nl.

Funding

KWF Kankerbestrijding TRANSCAN 8352/TRS-2018-00000715KWF Kankerbestrijding UVA 2010-4738
6 · The paper itself

Abstract

backgroundLiquid biopsies offer less burdensome sensitive disease monitoring. Bone marrow (BM) metastases, common in various cancers including neuroblastoma, is associated with poor outcomes. In pediatric high-risk neuroblastoma most patients initially respond to treatment, but in the majority the disease recurs with only 40% long-term survivors, stressing the need for more sensitive detection of disseminated disease during therapy.

methodsTo validate sensitive neuroblastoma mRNA RT-qPCR BM testing, we prospectively assessed serial BM samples from 345 international high-risk neuroblastoma patients, treated in trials NB2004 (GPOH) or NBL2009 (DCOG), using PHOX2B, TH, DDC, CHRNA3, and GAP43 RT-qPCR mRNA markers and BM GD2-immunocytology. Association between BM-infiltration levels and event-free survival (EFS) and overall survival (OS) was estimated by using Cox regression models and Kaplan-Meier's methodology.

resultsBM infiltration >10% by RT-qPCR at diagnosis was prognostic for survival (adjusted hazard ratio (HR) 1.82 [95%CI 1.25-2.63] and 2.04 [1.33-3.14] for EFS and OS, respectively). Any post-induction RT-qPCR positivity correlated with poor EFS and OS, with a HR of 2.10 [1.27-3.49] and 1.76 [1.01-3.08] and 5-years EFS of 26.6% [standard error 5.2%] versus 60.4% [6.7] and OS of 43.8% [5.9] versus 65.7% [6.6] for RT-qPCR-positive patients versus RT-qPCR-negative patients. In contrast, post-induction immunocytology positivity was not associated with EFS or OS (HR 1.22 [0.68-2.19] and 1.26 [0.54-2.42]).

conclusionThis study validates the association of not clearing of BM metastases by sensitive RT-qPCR detection with very poor outcome. We therefore propose implementation of RT-qPCR for minimal residual disease testing in neuroblastoma to guide therapy.

Indexed as

NeuroblastomaBiomarkers, TumorChildChild, PreschoolFemaleHumansInfantLiquid BiopsyMalePrognosisProspective StudiesReal-Time Polymerase Chain ReactionBiomarkers, Tumor

Identifiers

PMID39722049
PMCPMC11670466

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.