Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy

Coco, Simona; Alama, Angela; Vanni, Irene; Fontana, Vincenzo; Genova, Carlo; Bello, Maria Giovanna Dal; Truini, Anna; Rijavec, Erika; Biello, Federica; Sini, Claudio; Burrafato, Giovanni; Maggioni, C.; Barletta, Giulia; Grossi, Francesco

doi:10.3390/ijms18051035

Cited by 43 publications

(44 citation statements)

References 41 publications

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“…Compared to patients with benign tumors and healthy controls, the concentrations of circulating cfDNA were significantly distinguished and higher in adult patients with various cancers, including lung cancer, colorectal cancer, and breast cancer. Moreover, a great number of researchers have demonstrated that plasma DNA could be applied to estimate the therapy response and prognosis of broad cancers in the clinic . Generally, increased levels of cfDNA were closely correlated with exacerbation or poor outcomes in cancer patients.…”

Section: Discussionmentioning

confidence: 99%

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Plasma cell‐free DNA quantification is highly correlated to tumor burden in children with neuroblastoma

Wang

Wang²,

et al. 2018

Cancer Medicine

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To evaluate plasma cell‐free DNA (cfDNA) as a promising biomarker for neuroblastoma (NB) tumor burden. Seventy‐nine eligible patients with newly diagnosed NB were recruited from Beijing Children's Hospital between April 2016 and April 2017. Additionally, from September 2011 to June 2017, 79 patients with stable NB were evaluated with a median follow‐up time of 21 months. Approximately 2 mL of peripheral blood was drawn upon enrollment, and plasma cfDNA levels were measured via quantitative polymerase chain reaction (qPCR). Total cfDNA analysis was performed using the long interspersed nuclear element 1 (LINE‐1) 79 bp fragment, and DNA integrity was calculated by the ratio of the LINE‐1 300 bp fragment to the LINE‐1 79 bp fragment. A total of 79 NB patients with a median age of 36 months comprised the group of newly diagnosed NB patients. The main primary tumor site was the retroperitoneal and adrenal region (81%). Three or more metastatic sites were found in 17.7% of patients. Stable NB patients older than 18 months comprised 98.7% of the stable NB patients. Neuron‐specific enolase (NSE), lactate dehydrogenase (LDH), and cfDNA levels were dramatically increased in the newly diagnosed NB patients and significantly different from those in the stable NB patients. Moreover, the concentration of cfDNA was much higher in patients with larger tumors. By analyzing the area under the receiver operator characteristic (ROC) curve (AUC), the areas of total cfDNA, NSE, and LDH levels were 0.953, 0.929, and 0.906, respectively. The sensitivity and specificity data clarified that the level of circulating cfDNA in plasma can be considered as a reliable biomarker for describing tumor load in NB. The plasma cfDNA concentration was as good as the levels of LDH and NSE to discriminate the tumor burden in children with NB.

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Section: Discussionmentioning

confidence: 99%

“…It is important and necessary to determine whether plasma cfDNA could serve as a biomarker for NB. Based on others reports, [9][10][11][12][13][14] it is feasible to introduce plasma cfDNA to evaluate the tumor burden in NB patients. The method is reproducible and convenient.…”

Section: Introductionmentioning

confidence: 99%

Plasma cell‐free DNA quantification is highly correlated to tumor burden in children with neuroblastoma

Wang

Wang²,

et al. 2018

Cancer Medicine

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“…On the contrary, Coco and colleagues showed an inverse but non significant relationship between baseline CTC number (6 CTC/3 mL of blood) and OS in 73 NSCLC patients (stage IIIB-IV) candidates for palliative first-line platinum-based chemotherapy. The authors hypothesized that a higher baseline number of heterogeneous CTC populations could exhibit different responsiveness to chemotherapy [14].…”

Section: Circulating Tumor Cellsmentioning

confidence: 99%

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Rijavec

Coco

Genova

et al. 2019

Cancers

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Non-small cell lung cancer is one leading cause of death worldwide, and patients would greatly benefit from an early diagnosis. Since targeted and immunotherapies have emerged as novel approaches for more tailored treatments, repeated assessments of the tumor biology have become pivotal to drive clinical decisions. Currently, tumor tissue biopsy is the gold standard to investigate potentially actionable biomarkers, but this procedure is invasive and may prove inadequate to represent the whole malignancy. In this regard, liquid biopsy represents a minimally invasive and more comprehensive option for early detection and investigation of this tumor. Today, cell-free DNA is the only approved circulating marker to select patients for a targeted therapy. Conversely, the other tumor-derived markers (i.e., circulating tumor cells, miRNAs, exosomes, and tumor educated platelets) are still at a pre-clinical phase, although they show promising results for their application in screening programs or as prognostic/predictive biomarkers. The main challenges for their clinical translation are the lack of reliable cutoffs and, especially for miRNAs, the great variability among the studies. Moreover, no established tool has been approved for circulating tumor cells and exosome isolation. Finally, large prospective clinical trials are mandatory to provide evidence of their clinical utility.

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“…Plasma cell-free DNA (cfDNA) has become an increasingly attractive potential biomarker for various cancers [16][17][18]. Typically, cfDNA consists of degraded DNA fragments derived from tumor cells undergoing apoptosis or necrosis.…”

Section: Introductionmentioning

confidence: 99%

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

Wang²,

Jiang

et al. 2020

BMC Cancer

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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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Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy

Cited by 43 publications

References 41 publications

Plasma cell‐free DNA quantification is highly correlated to tumor burden in children with neuroblastoma

Plasma cell‐free DNA quantification is highly correlated to tumor burden in children with neuroblastoma

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

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

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