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Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma.

ABSTRACT: BACKGROUND: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 thus an urgent need to identify effective predictive biomarkers of disease recurrence. METHODS:A 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. RESULTS:Of 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. CONCLUSIONS:High plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.

SUBMITTER: Su Y

PROVIDER: S-EPMC7006086 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma.

Su Yan Y Wang Lijun L Jiang Chiyi C Yue Zhixia Z Fan Hongjun H Hong Huimin H Duan Chao C Jin Mei M Zhang Dawei D Qiu Lihua L Cheng Xianfeng X Xu Zhong Z Ma Xiaoli X

BMC cancer 20200206 1

<h4>Background</h4>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 thus an urgent need to identify effective predictive biomarkers of disease recurrence.<h4>Methods</h4>A 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 treatmen ...[more]

PMID: 32028911

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Project description:ObjectiveBy virtue of largely disparate clinical outcomes of prostate cancer (PCA), there is a pressing need to search for useful biomarkers for PCA prognosis. Cell-free DNA (cfDNA) is a promising biomarker for detecting, monitoring, and predicting survival of prostate cancer (PCA). However, the utility of total cfDNA quantitation in PCA in clinical setting remains elusive. Here, we performed a thorough meta-analysis to assess the prognostic value of cfDNA concentration for patients with PCA. In addition, we tested the possibility of the combination of PSA and cfDNA test results to improve the prediction power in PCA prognosis.Method and materialsMore than six databases, including PubMed, Web of Science, Medline, PMC, EMBASE and the Cochrane Library were searched. Results yielded all eligible articles from the date of inception to June 30, 2020. Continuous, diagnostic, and prognostic variables in cfDNA in PCA were included in the meta-analysis by STATA.ResultsA total of 23 articles were enrolled in our meta-analysis: 69.6% (16/23) were related to diagnosis, and 56.5% (13/23) were related to prognosis. The pooled concentration of cfDNA in PCA patients was significantly higher than in the control group (SMD = 0.89, 95%CI = 0.53, 1.26), mirroring results for the prostate-specific antigen (PSA). For the detection test variables, the SROC with 95%CI was 0.87 (0.84-0.90) for cfDNA concentration. In terms of prognostic variables, the concentrations of cfDNA were significantly related with progression-free survival (PFS, logHR = 0.84 (95%CI0.39, 1.28) and overall survival [OS, log HR = 0.60 (95%CI0.29, 0.90)]. Lastly, the test showed no significant publication bias in the present meta-analysis, excluding the diagnostic meta-analysis.ConclusionsThe concentration of cell-free DNA is high in the prostate cancer patients. The present study substantiates the prognostic value of the cfDNA concentration. High concentration cfDNA correlates with poor disease outcome of CRPC. The study cohort with large sample size is needed to evaluate the prognosis value of cfDNA in the future. We also emphasized that combination of PSA and cf DNA quantitation is important in future large individual meta study.

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Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma.

Publications

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma.

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