Serial ctDNA and Molecular Residual Disease Monitoring in Neuroblastoma

Overview

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.

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.