The correlation between cell-free DNA and tumour burden was estimated by PET/CT in patients with advanced NSCLC

Nygaard, Anneli Dowler; Holdgaard, Paw; Spindler, Karen Lise Garm; Pallisgaard, Niels; Jakobsen, Anders

doi:10.1038/bjc.2013.705

Cited by 99 publications

(84 citation statements)

References 30 publications

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“…Nevertheless, it is the first time, to our knowledge, that this parameter has been studied simultaneously on two different genes by targeting either a KRAS or a BRAF WT sequence highlighting the robustness of our analytic process and the robustness of the prognostic significance of total ccfDNA concentration. Previous observations of our group on xenografted mice have shown the strong correlation between tumor volume and ccfDNA concentration (33), and other works have showed that ccfDNA concentration is positively correlated to tumor burden (7,28,34). Spindler and colleagues (8) revealed the correlation between the concentration of mutant ccfDNA (mA) and OS.…”

Section: Discussionmentioning

confidence: 81%

“…Tumor cells release ccfDNA, which exhibits the genetic and epigenetic alterations of the tumor of origin (4). The clinical significance of tumor-derived ccfDNA released in the blood of patients with colorectal cancer has already been investigated as a prognostic tool in previous studies using various technologic approaches (5)(6)(7)(8)(9). In a recent large meta-analysis, a high correlation between ccfDNA concentration and mCRC patient survival was observed, revealing that patients with relatively low levels of ccfDNA lived significantly longer than patients with higher levels (6).…”

Section: Introductionmentioning

confidence: 99%

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Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Messaoudi

Moulière

Manoir

et al. 2016

Clinical Cancer Research

148

108

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Purpose: Circulating cell-free DNA (ccfDNA) is a valuable source of tumor material obtained from a simple blood sampling that enables noninvasive analysis of the tumor genome. Our goal was to carry out a multiparametric analysis of ccfDNA and evaluate its prognostic value by investigating the overall survival (OS) of 97 metastatic colorectal cancer patients (mCRC).Experimental Design: Qualitative parameters (determination of the main KRAS exon2 and BRAF V600E mutations) and quantitative parameters (total ccfDNA concentration, mutant ccfDNA concentration, the proportion of mutant ccfDNA, and ccfDNA integrity index) were determined simultaneously in a single run using a unique Q-PCR multimarker approach (100% success rate).Results: The median follow-up time was 36 months and median OS was 22 months. Patients showing high ccfDNA levels had significantly shorter OS (18.07 months vs. 28.5 months, P ¼ 0.0087). Moreover, multivariate analysis revealed that a high ccfDNA level is an independent prognostic factor (P ¼ 0.034). All ccfDNA parameters were of prognostic interest: patients with higher levels of mutant ccfDNA and higher mutation loads for the detected mutations had shorter OS (P ¼ 0.0089 and P ¼ 0.05, respectively). In addition, the level of ccfDNA fragmentation correlated positively with decreased OS in the exclusive KRAS/ BRAF-mutant cohort of patients (P ¼ 0.0052) and appeared as a strong independent prognostic factor (P ¼ 0.0072), whereas it was not significant in the exclusive KRAS/BRAF WT cohort of patients (P ¼ 0.67).Conclusions: Our data provide for the first time qualitative and quantitative evidence in favor of multiparametric ccfDNA analysis in mCRC patients for prognostic assessment.

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Messaoudi

Moulière

Manoir

et al. 2016

Clinical Cancer Research

148

108

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“…In contrast, Morelli et al recently measured the sums of lesion volumes measured (manually on each image, by three independent readers in a total of 23 patients), but found no significant correlation between tumor volume and percentage of acquired mutant reads in the plasma [78]. In a Danish group of patients with mCRC, both total cfDNA and mutated DNA were analyzed in relation to positron emission tomography-computed tomography (PET-CT) parameters similar to a study published in lung cancer [79]. Data revealed a weak correlation to quantitative measures of both total and mutated DNA [33].…”

Section: Methodsmentioning

confidence: 99%

Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer

Spindler

2016

Acta Oncologica

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Background: Circulating DNA can be used to measure the total cell-free DNA (cfDNA) and for detection and quantification of tumor-specific genetic alterations in the peripheral blood, and the broad clinical potential of circulating DNA has attracted increasing focus over the past decade. Concentrations of circulating DNA are high in metastatic colorectal cancer (CRC), and the total levels of cfDNA have been reported to hold strong prognostic value. Colorectal tumors are characterized by a high frequency of well known, clinically relevant genetic alteration, which is readily detected in the cfDNA and holds potential for tailoring of palliative therapy and for monitoring during treatment. This review aims to present the current literature which has specifically reported data on the potential utility of cfDNA and on tumor-specific mutations in metastatic colorectal cancer (mCRC). Method: Methodological, biological and clinical aspects are discussed based on the most recent development in this specific setting, and eligible studies were identified by systematic literature searched from Pubmed and EMBASE in addition to conference papers and communications. Results: The literature regarding cfDNA in CRC is broad and heterogeneous concerning aims, nomenclature, methods, cohorts and clinical endpoints and consequently difficult to include in a single systematic search. However, the available data underline a strong clinical value of measuring both total cfDNA levels and tumor-specific mutations in the plasma of patients with mCRC, pre-and during systemic therapy. Conclusion: This paper had gathered the most recent literature on several aspects of cfDNA in mCRC, including methodological, biological and clinical aspects, and discussed the large clinical potential in this specific setting, which needs to be validated in carefully designed prospective studies in statistically relevant cohorts.

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“…It has been shown that higher pretreatment ctDNA levels were associated with worse OS in patients who were treated with first-line platinum doublet chemotherapy (16.8 vs. 22.4 months) (15). In another report, increased plasma ctDNA levels were correlated with advanced tumor stage, tumor progression after chemotherapy as well as poor survival (16,17).…”

Section: Circulating (Cell-free) Tumor Dna (Ctdna)mentioning

confidence: 99%

Blood-based biomarkers in lung cancer: prognosis and treatment decisions

Xu‐Welliver¹,

Carbone²

2017

Transl. Lung Cancer Res.

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Despite recent advances, non-small cell lung cancer (NSCLC) remains a devastating disease with overall poor prognosis. Major contributing factors include obstacles to diagnosing the disease early in its course during the asymptomatic stage as well as diversity and complexity of its biology underlying tumorigenesis and tumor progression. Advances in molecularly targeted therapies which drives the development of personalized cancer care require precise and comprehensive understanding of tumor biology, not only at the time of diagnosis but also during treatment course and surveillance. As lung tumor tissue can be difficult to obtain without invasive and potentially risky procedures, it is difficult to monitor treatment response with serial tissue biopsies. Development of non-invasive but reliable blood based tumor markers has become an important research area. In this review, we focus on the following circulating biomarkers that have been identified in recent years: circulating tumor cells (CTCs); circulating cell-free nucleic acids, such as circulating tumor DNA (ctDNA) and microRNA (miR); and other biomarkers such as genomic and proteomic features. These biomarkers not only have prognostic values, but also can help guild treatment decisions by monitoring tumor burden, detecting minimal residual disease and/or recurrent disease, as well as monitoring evolution of genetic alterations throughout the treatment course.

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The correlation between cell-free DNA and tumour burden was estimated by PET/CT in patients with advanced NSCLC

Cited by 99 publications

References 30 publications

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer

Blood-based biomarkers in lung cancer: prognosis and treatment decisions

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