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

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...

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Autores principales: Su, Yan, Wang, Lijun, Jiang, Chiyi, Yue, Zhixia, Fan, Hongjun, Hong, Huimin, Duan, Chao, Jin, Mei, Zhang, Dawei, Qiu, Lihua, Cheng, Xianfeng, Xu, Zhong, Ma, Xiaoli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006086/
https://www.ncbi.nlm.nih.gov/pubmed/32028911
http://dx.doi.org/10.1186/s12885-020-6562-8
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author Su, Yan
Wang, Lijun
Jiang, Chiyi
Yue, Zhixia
Fan, Hongjun
Hong, Huimin
Duan, Chao
Jin, Mei
Zhang, Dawei
Qiu, Lihua
Cheng, Xianfeng
Xu, Zhong
Ma, Xiaoli
author_facet Su, Yan
Wang, Lijun
Jiang, Chiyi
Yue, Zhixia
Fan, Hongjun
Hong, Huimin
Duan, Chao
Jin, Mei
Zhang, Dawei
Qiu, Lihua
Cheng, Xianfeng
Xu, Zhong
Ma, Xiaoli
author_sort Su, Yan
collection PubMed
description 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.
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spelling pubmed-70060862020-02-11 Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma Su, Yan Wang, Lijun Jiang, Chiyi Yue, Zhixia Fan, Hongjun Hong, Huimin Duan, Chao Jin, Mei Zhang, Dawei Qiu, Lihua Cheng, Xianfeng Xu, Zhong Ma, Xiaoli BMC Cancer Research Article 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. BioMed Central 2020-02-06 /pmc/articles/PMC7006086/ /pubmed/32028911 http://dx.doi.org/10.1186/s12885-020-6562-8 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Su, Yan
Wang, Lijun
Jiang, Chiyi
Yue, Zhixia
Fan, Hongjun
Hong, Huimin
Duan, Chao
Jin, Mei
Zhang, Dawei
Qiu, Lihua
Cheng, Xianfeng
Xu, Zhong
Ma, Xiaoli
Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma
title Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma
title_full Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma
title_fullStr Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma
title_full_unstemmed Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma
title_short Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma
title_sort increased plasma concentration of cell-free dna precedes disease recurrence in children with high-risk neuroblastoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006086/
https://www.ncbi.nlm.nih.gov/pubmed/32028911
http://dx.doi.org/10.1186/s12885-020-6562-8
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