Abstract
BackgroundNeuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is thus an urgent need to identify effective predictive biomarkers of disease recurrence.MethodsA total of 116 patients with high-risk neuroblastoma were recruited at Beijing Children’s Hospital between February 2015 and December 2017. All patients received multidisciplinary treatment, were evaluated for the therapeutic response, and then initiated on maintenance treatment. Blood samples were collected at the beginning of maintenance treatment, every 3 months thereafter, and at the time of disease recurrence. Plasma levels of cell-free DNA (cfDNA) were quantified by qPCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of plasma cfDNA concentration to predict recurrence.ResultsOf the 116 patients, 36 (31.0%) developed recurrence during maintenance treatment. The median time to recurrence was 19.00, 9.00, and 8.00 months for patients who had achieved complete response (n = 6), partial response (n = 25), and stable disease (n = 5), respectively, after multidisciplinary treatment. The median plasma cfDNA concentration at the time of recurrence was significantly higher than the concentration in recurrence-free patients throughout maintenance treatment (29.34 ng/mL vs 10.32 ng/mL). Patients recorded a plasma cfDNA level ≥ 29 ng/mL an average of 0.55 months before diagnosis of disease recurrence. ROC analysis of the power of plasma cfDNA to distinguish between patients with or without recurrence yielded an area under the curve of 0.825, with optimal sensitivity and specificity of 80.6 and 71.3%, respectively, at a cfDNA level of 12.93 ng/mL.ConclusionsHigh plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.
Highlights
Neuroblastoma is the most common extracranial solid tumor of childhood
We found that a high level of plasma cell-free DNA (cfDNA) preceded disease recurrence and had good discriminatory power, suggesting that it could be used as a molecular marker of NB progression in the clinic
Demographic and clinical characteristics A total of 116 pediatric patients (56 female, 60 male) with high-risk NB were enrolled at the beginning of maintenance treatment (Table 1)
Summary
Neuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is an urgent need to identify effective predictive biomarkers of disease recurrence. CfDNA consists of degraded DNA fragments derived from tumor cells undergoing apoptosis or necrosis. Such fragments are normally taken up by tissue macrophages, excessive release of DNA from large tumors can result in some reaching the bloodstream. This observation hinted at the possibility that circulating cfDNA could be used to monitor cancer progression [3, 19, 20]. Little is known about plasma cfDNA concentration in patients with NB or its potential value as a biomarker for disease recurrence
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