Serial ctDNA and Molecular Residual Disease Monitoring in Neuroblastoma

A Prospective Observational Study of Serial Circulating Tumor DNA and Molecular Residual Disease Monitoring for Molecular Profiling, Treatment Response Assessment, and Early Relapse Detection in Patients With Neuroblastoma

This prospective observational study evaluates serial circulating tumor DNA (ctDNA) and molecular residual disease (MRD) monitoring in patients with neuroblastoma. The study aims to characterize baseline genomic alterations, assess ctDNA detectability and dynamic changes during treatment and follow-up, compare tumor-informed personalized MRD assays with fixed-panel assays, and determine the clinical utility of ctDNA/MRD for treatment response assessment, molecular remission evaluation, relapse surveillance, and early detection of disease progression.

Study Overview

• Status: Recruiting
• Conditions: Neuroblastoma

Detailed Description

Neuroblastoma is a biologically and clinically heterogeneous pediatric malignancy. Despite multimodal therapy, a substantial proportion of patients, particularly those with high-risk disease, experience relapse or treatment resistance. Current disease assessment relies on imaging, bone marrow evaluation, serum markers, and tissue-based molecular testing, but these methods may not adequately reflect real-time tumor dynamics, molecular evolution, or minimal residual disease.

Circulating tumor DNA (ctDNA) analysis provides a minimally invasive approach for serial molecular profiling and disease monitoring. In neuroblastoma, ctDNA and molecular residual disease (MRD) testing may help identify baseline genomic alterations, evaluate treatment response, detect persistent molecular disease after surgery or systemic therapy, and provide earlier warning of relapse or progression than conventional clinical assessment in selected patients.

This study prospectively enrolls patients with neuroblastoma, including newly diagnosed and relapsed/refractory cases, and collects serial biospecimens during routine clinical care. Plasma samples are obtained at predefined time points including baseline, during treatment, after surgery when applicable, during post-treatment surveillance, and at suspected relapse or progression. In selected patients, bone marrow and/or cerebrospinal fluid specimens may also be analyzed according to disease status and sample availability. Molecular testing includes tumor-informed personalized MRD assays and/or fixed-panel liquid biopsy assays according to protocol-defined sample availability and assay feasibility.

The study evaluates baseline molecular profiling, ctDNA detectability, dynamic ctDNA/MRD changes during therapy, concordance with clinical response, molecular clearance, and early molecular detection of relapse or progression. Additional analyses include associations between baseline ctDNA metrics and disease stage, risk classification, metastatic status, and other clinicopathologic variables, as well as comparison of the clinical consistency of personalized MRD assays versus fixed-panel approaches.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Yizhuo Zhang, Doctor of Haematology; Phone Number: +86 18819241079; Email: zhangyzh@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Yizhuo Zhang Professor, Chief Physician, Doctor; Email: zhangyzh@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Child, Adult

Description

Inclusion Criteria:

• Patients with histologically or clinically confirmed neuroblastoma according to institutional or protocol-defined diagnostic criteria.

Newly diagnosed, relapsed, refractory, or progressive neuroblastoma eligible for serial biospecimen collection during routine clinical care.

Availability of peripheral blood samples for ctDNA/MRD analysis at baseline and/or longitudinal follow-up time points.

Availability of clinical data required for molecular-clinical correlation analyses, including response and outcome assessment.

Availability of tumor tissue and matched control samples for tumor-informed assay development, if applicable and feasible.

Written informed consent from a parent or legal guardian, and assent from the participant when applicable.

Exclusion Criteria:

• Inability to provide protocol-required blood samples for ctDNA/MRD testing. Insufficient clinical information for protocol-defined response or outcome analyses.

Poor-quality or insufficient biospecimens that preclude molecular analysis, when molecular testing is a required component of the study dataset.

Any condition that, in the opinion of the investigator, would make study participation inappropriate.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Newly Diagnosed Neuroblastoma Cohort; Patients with newly diagnosed neuroblastoma undergoing protocol-defined serial ctDNA/MRD monitoring during treatment and follow-up.
Relapsed or Refractory Neuroblastoma Cohort; Patients with relapsed, refractory, or progressive neuroblastoma undergoing serial ctDNA/MRD monitoring during salvage treatment and follow-up.
Adult Neuroblastoma Cohort; Adult patients with neuroblastoma undergoing serial ctDNA/MRD monitoring for molecular characterization and disease surveillance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Concordance of Serial ctDNA/MRD Dynamics With Disease Status	Proportion of evaluable patients in whom longitudinal ctDNA/MRD status is concordant with protocol-defined clinical disease status, including treatment response, molecular remission, relapse, or progression.	From baseline through follow-up, up to 36 months
Rate of Baseline ctDNA Detectability	Proportion of enrolled patients with detectable tumor-derived alterations in baseline plasma ctDNA/cfDNA samples.	At baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Clinical Concordance Between Personalized MRD Assays and Fixed-Panel Assays	Comparison of the proportion of patients with ctDNA/MRD dynamics concordant with clinical disease status between tumor-informed personalized MRD assays and fixed-panel liquid biopsy assays.	From baseline through follow-up, up to 36 months
Association Between ctDNA/MRD Clearance and Best Clinical Response	Association between ctDNA/MRD clearance during treatment and best clinical response, including complete response and partial response, as defined by protocol-specified clinical assessment.	From baseline through end of treatment, up to 24 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: neuroblastoma; ctDNA; disease monitoring; molecular residual disease
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neuroblastoma
• Other Study ID Numbers: NB-ctDNA-2024-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO