Neuroblastoma
Conditions
Keywords
ctDNA, molecular residual disease, neuroblastoma, disease monitoring
Brief summary
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.
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.
Interventions
None listed
Sponsors
Sun Yat-sen University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Concordance of Serial ctDNA/MRD Dynamics With Disease Status | From baseline through follow-up, up to 36 months | 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. |
| Rate of Baseline ctDNA Detectability | At baseline | Proportion of enrolled patients with detectable tumor-derived alterations in baseline plasma ctDNA/cfDNA samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Clinical Concordance Between Personalized MRD Assays and Fixed-Panel Assays | From baseline through follow-up, up to 36 months | 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. |
| Association Between ctDNA/MRD Clearance and Best Clinical Response | From baseline through end of treatment, up to 24 months | Association between ctDNA/MRD clearance during treatment and best clinical response, including complete response and partial response, as defined by protocol-specified clinical assessment. |
Countries
China
Contacts
CONTACTYizhuo Zhang, Doctor of Haematology
Outcome results
None listed