Serial ctDNA and Molecular Residual Disease Monitoring in Neuroblastoma

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.

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.