scholarly journals High concentration of plasma cell free DNA alerting disease recurrence in high risk neuroblastoma children

2019 ◽  
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Hongjun Fan ◽  
...  
Keyword(s):  
High Risk ◽  
Plasma Cell ◽  
Maintenance Treatment ◽  
Treatment Phase ◽  
Disease Recurrence ◽  
High Rate ◽  
High Concentration ◽  
Cell Free Dna ◽  
Free Dna ◽  
High Level

Abstract Background Neuroblastoma is the third-most common cancer in children. The high rate of tumor recurrence accounts for a low survival rate in high risk neuroblastoma. Therefore it is clinically of extreme importance to find an effective biomarker for alerting disease recurrence.Methods Total 116 high risk neuroblastoma patients were recruited in Beijing Children’s Hospital from February, 2015 to December, 2017. All patients had received multiple-disciplinary treatment, then went into maintenance treatment phase after evaluation. Blood samples were collected to quantify plasma cell-free DNA (cfDNA) at time points of the beginning of maintenance treatment, every three months afterwards, and diagnosis of recurrence.Results Results showed that 36 high risk neuroblastoma patients developed recurrence during maintenance treatment. The plasma cfDNA concentration was significantly higher in recurrence than in event-free patients (29.34 ng/ml VS 10.32 ng/ml). The time span of cfDNA level higher than 29 ng/ml was consistently detected ahead of recurrence at mean of 0.55 months. The ROC analysis showed that AUC was 0.825, optimal sensitivity and specificity of 80.6% and 71.3% respectively, at cfDNA level of 12.93 ng/ml.Conclusions We concluded that high level of plasma cfDNA could serve as a promising molecular marker to alert recurrence disease in high risk neuroblastoma children.

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

2020 ◽  
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Hongjun Fan ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Treatment ◽  
Roc Analysis ◽  
Treatment Phase ◽  
Disease Recurrence ◽  
High Rate ◽  
Cell Free Dna ◽  
Free Dna ◽  
High Level ◽  
Cancer In Children

Abstract Background Neuroblastoma is the third-most common cancer in children. The high rate of tumor recurrence accounts for a low survival rate in high risk neuroblastoma. Therefore it is clinically of extreme importance to find an effective biomarker for alerting disease recurrence.Methods Total 116 high risk neuroblastoma patients were recruited in Beijing Children's Hospital from February, 2015 to December, 2017. All patients had received multiple-disciplinary treatment, then went into maintenance treatment phase after evaluation. Blood samples were collected to quantify plasma cell-free DNA (cfDNA) at time points of the beginning of maintenance treatment, every three months afterwards, and diagnosis of recurrence.Results Results showed that 36 high risk neuroblastoma patients developed recurrence during maintenance treatment. The plasma cfDNA concentration was significantly higher in recurrence than in event-free patients (29.34 ng/ml VS 10.32 ng/ml). The time span of cfDNA level higher than 29 ng/ml was consistently detected ahead of recurrence at mean of 0.55 months. The ROC analysis showed that AUC was 0.825, optimal sensitivity and specificity of 80.6% and 71.3% respectively, at cfDNA level of 12.93 ng/ml.Conclusions We concluded that high level of plasma cfDNA could serve as a promising molecular marker to alert recurrence disease in high risk neuroblastoma children.

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

2020 ◽  
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Hongjun Fan ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Treatment ◽  
Multidisciplinary Treatment ◽  
Area Under The Curve ◽  
Predictive Biomarkers ◽  
Disease Recurrence ◽  
High Rate ◽  
Roc Curve Analysis ◽  
Cell Free Dna ◽  
Free Dna

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.

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

2020 ◽  
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Hongjun Fan ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Treatment ◽  
Multidisciplinary Treatment ◽  
Area Under The Curve ◽  
Predictive Biomarkers ◽  
Disease Recurrence ◽  
High Rate ◽  
Roc Curve Analysis ◽  
Cell Free Dna ◽  
Free Dna

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.

Plasma cell-free DNA for noninvasive molecular profiling in high-risk stage 4 neuroblastoma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 10554-10554 ◽  
Author(s):  
Prachi Kothari ◽  
Julie Yang ◽  
Michael F. Berger ◽  
Neerav Narendra Shukla ◽  
Shakeel Modak ◽  
...  
Keyword(s):  
High Risk ◽  
Plasma Cell ◽  
Molecular Profiling ◽  
Cell Free Dna ◽  
Free Dna ◽  
Stage 4

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

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Hongjun Fan ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
High Risk ◽  
Disease Recurrence ◽  
Cell Free Dna ◽  
Free Dna

High concentration of plasma cell free DNA alerted progressive and recurrent disease in children with high risk neuroblastoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21506-e21506
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Fan Hongjun ◽  
...  
Keyword(s):  
High Risk ◽  
Recurrent Events ◽  
Recurrent Disease ◽  
Evaluation Criteria ◽  
High Concentration ◽  
Cell Free Dna ◽  
Free Dna ◽  
Maintenance Stage ◽  
Important Time ◽  
Event Rates

e21506 Background: Neuroblastoma (NB) happens most frequently among babies and it is also the third-most common cancer in children after leukemia and brain tumor. The unexpected occurrence of NB progression and relapse accounts for the low survival free event rates, therefore finding an effective biomarker to predict the progressive and recurrent events is urgent. Methods: A total of 116 NB patients with high risk (HR-NB) from Beijing Children’s Hospital between February 1, 2015 and December 31, 2017 were recruited. All patients received the regular multiple-disciplinary treatments and then followed the evaluation for therapeutic response according to the standards of Response Evaluation Criteria in Solid Tumors (RECIST). Blood samples were collected to quantify cell-free DNA levels at important time points including one week before or the beginning of maintenance stage, every or every three month after the beginning of maintenance stage, diagnosis of progression and recurrence. Results: Results showed that 36 HR-NB patients developed progressive disease (PD) and recurrent disease. More intriguingly, cfDNA concentration was extremely higher in NB patients with progression and recurrence than those with events free (29.34 ng/ml VS 10.32 ng/ml), and increasing cfDNA levels happened at least 0.55 months before the progression and recurrence was confirmed. By analyzing the area under the receiver operator characteristic (ROC) curve (AUC), it showed that the area of cfDNA level was 0.67 at 12.93 ng/ml with 62.5% sensitivity and 71.3% specificity. Conclusions: Taken together, it was suggested increasing cfDNA concentration in plasma may benefit to warn the incurrence of progression and recurrence in NB patients in clinic, which will help clinicians win much more valuable time to save patients’ lives.

Genomic variations in plasma cell free DNA differentiate early stage lung cancers from normal controls

Lung Cancer ◽  
2015 ◽  
Vol 90 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Shu Xia ◽  
Chiang-Ching Huang ◽  
Min Le ◽  
Rachel Dittmar ◽  
Meijun Du ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Early Stage ◽  
Cell Free Dna ◽  
Lung Cancers ◽  
Genomic Variations ◽  
Free Dna ◽  
Normal Controls

scholarly journals PATH-27. MUTATION DETECTION USING PLASMA CELL-FREE DNA IN CHILDREN WITH CENTRAL NERVOUS SYSTEM TUMORS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii430-iii430
Author(s):  
Ross Mangum ◽  
Jacquelyn Reuther ◽  
Koel Sen Baksi ◽  
Ryan C Zabriskie ◽  
Ilavarasi Gandhi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Plasma Cell ◽  
Pediatric Patients ◽  
Cns Tumors ◽  
Cell Free Dna ◽  
Pilot Studies ◽  
Dna And Rna ◽  
Free Dna ◽  
Initial Cohort

Abstract BACKGROUND The role of plasma cell-free DNA (cfDNA) as a cancer biomarker for tracking treatment response and detecting early relapse has been well described for solid tumors outside the central nervous system (CNS). However, the presence of a blood-brain barrier complicates the application of plasma cfDNA analysis for patients with CNS malignancies. METHODS cfDNA was extracted from plasma of pediatric patients with CNS tumors utilizing a QIAmp® MinElute® kit and quantitated with Qubit 2.0 Fluorometer. Extensive genomic testing, including targeted DNA and RNA solid tumor panels, exome and transcriptome sequencing, as well as copy number array, was performed on matched tumor samples as part of the Texas KidsCanSeq study. An Archer® Reveal ctDNA28 NGS kit was then used for assaying the sensitivity of detecting tumor-specific mutations in the plasma of these patients. RESULTS A median of 10.7ng cfDNA/mL plasma (Interquartile range: 6.4 – 15.3) was extracted from 78 patients at time of study enrollment. Longitudinal samples from 24 patients exhibited a median yield of 7.7ng cfDNA/mL plasma (IQR: 5.9 – 9.1). An initial cohort of 6 patients was identified with 7 somatic variants covered by the Archer® Reveal kit. Four of seven mutations identified in matched tumor specimens were detected in patient plasma at variant allele frequencies ranging from 0.2–1%. CONCLUSIONS While challenging, detection of cfDNA in the plasma of pediatric patients with CNS tumors is possible and is being explored in a larger patient cohort along with pilot studies investigating cerebrospinal fluid as an additional source for tumor-specific cfDNA.

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