Multi-Purpose Utility of Circulating Plasma DNA Testing in Patients with Advanced Cancers

Perkins, Géraldine; Yap, Timothy A.; Pope, Lorna; Mulick, Amy; Dukes, Juliet; Riisnaes, Ruth; Massard, Christophe; Cassier, Philippe; Miranda, Susana; Clark, Jeremy; Denholm, Katie Ann; Thway, Khin; Castro, David González de; Attard, Gerhardt; Molife, L Rhoda; Kaye, Stan B.; Banerji, Udai; Bono, Johann S. de

doi:10.1371/journal.pone.0047020

Cited by 133 publications

(107 citation statements)

References 28 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In general, the levels are higher in mCRC patients than in healthy controls, as shown in Table 1 [15,20,47,58,[63][64][65][66][67][68][69][70][71][72]; and the levels have some correlation to stage as reported in a limited number of studies [15,41,68,73] in primary CRC. These findings give important biological information, and researchers suggest that cfDNA has potential as a diagnostic or screening tool; a potential that is currently being investigated by several groups.…”

Section: Methodsmentioning

confidence: 71%

“…Furthermore, analysis of samples from a large normal cohort enabled definition of an upper normal limit [57]. In addition, the levels of cfDNA seem stable between different cohorts of CRC patients, (whereas some differences seem to exist between different tumor types as illustrated in the data from Perkins et al [64]). A systematic review and meta analysis, including more than 1000 patients, indicates a strong and consistant prognostic value of total cfDNA in favor of the patients with the lowest levels of the marker [85].…”

Section: Clinical Utility Of Total Cell-free Dnamentioning

confidence: 99%

See 1 more Smart Citation

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

Spindler

2016

Acta Oncologica

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 71%

Section: Clinical Utility Of Total Cell-free Dnamentioning

confidence: 99%

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

Spindler

2016

Acta Oncologica

View full text Add to dashboard Cite

show abstract

“…11,24,30,31). To introduce the liquid biopsy in the clinical management of cancer patients, it is important that these parameters be standardized for consensus analysis and reporting (32).…”

Section: Discussionmentioning

confidence: 99%

Circulating Cell-Free Tumor DNA Analysis of 50 Genes by Next-Generation Sequencing in the Prospective MOSCATO Trial

Jovelet

Ileana

Deley

et al. 2016

Clinical Cancer Research

Self Cite

101

View full text Add to dashboard Cite

Purpose: Liquid biopsies based on circulating cell-free DNA (cfDNA) analysis are described as surrogate samples for molecular analysis. We evaluated the concordance between tumor DNA (tDNA) and cfDNA analysis on a large cohort of patients with advanced or metastatic solid tumor, eligible for phase I trial and with good performance status, enrolled in MOSCATO 01 trial (clinical trial NCT01566019).Experimental Design: Blood samples were collected at inclusion and cfDNA was extracted from plasma for 334 patients. Hotspot mutations were screened using next-generation sequencing for 50 cancer genes.Results: Among the 283 patients with tDNA-cfDNA pairs, 121 had mutation in both, 99 in tumor only, 5 in cfDNA only, and for 58 patients no mutation was detected, leading to a 55.0% estimated sensitivity [95% confidence interval (CI), 48.4%-61.6%] at the patient level. Among the 220 patients with mutations in tDNA, the sensitivity of cfDNA analysis was significantly linked to the number of metastatic sites, albumin level, tumor type, and number of lines of treatment. A sensitivity prediction score could be derived from clinical parameters. Sensitivity is 83% in patients with a high score (!8). In addition, we analyzed cfDNA for 51 patients without available tissue sample. Mutations were detected for 22 patients, including 19 oncogenic variants and 8 actionable mutations.Conclusions: Detection of somatic mutations in cfDNA is feasible for prescreening phase I candidates with a satisfactory specificity; overall sensitivity can be improved by a sensitivity score allowing to select patients for whom cfDNA constitutes a reliable noninvasive surrogate to screen mutations.

show abstract

“…One study including 105 patients with solid tumors, who were referred for participation in phase I trials of molecularly targeted drugs using the Sequenom MassArray System and OncoCarta panel for somatic mutation profiling, demonstrated that a liquid biopsy was beneficial in advanced cancer patients when repeated tumor biopsy was not safely feasible and genomic analysis of archival tumor was deemed insufficient (75 ). Schwarzenbach et al conducted a multicenter study that recruited a cohort of 388 patients with primary breast cancer before chemotherapy and investigated LOH in a set of 8 genes (76 ).…”

Section: Clinical Implementation Of Liquid Biopsymentioning

confidence: 99%

Circulating Tumor DNA as a Liquid Biopsy for Cancer

2015

View full text Add to dashboard Cite

BACKGROUND Targeted therapies have markedly changed the treatment of cancer over the past 10 years. However, almost all tumors acquire resistance to systemic treatment as a result of tumor heterogeneity, clonal evolution, and selection. Although genotyping is the most currently used method for categorizing tumors for clinical decisions, tumor tissues provide only a snapshot, or are often difficult to obtain. To overcome these issues, methods are needed for a rapid, cost-effective, and noninvasive identification of biomarkers at various time points during the course of disease. Because cell-free circulating tumor DNA (ctDNA) is a potential surrogate for the entire tumor genome, the use of ctDNA as a liquid biopsy may help to obtain the genetic follow-up data that are urgently needed. CONTENT This review includes recent studies exploring the diagnostic, prognostic, and predictive potential of ctDNA as a liquid biopsy in cancer. In addition, it covers biological and technical aspects, including recent advances in the analytical sensitivity and accuracy of DNA analysis as well as hurdles that have to be overcome before implementation into clinical routine. SUMMARY Although the analysis of ctDNA is a promising area, and despite all efforts to develop suitable tools for a comprehensive analysis of tumor genomes from plasma DNA, the liquid biopsy is not yet routinely used as a clinical application. Harmonization of preanalytical and analytical procedures is needed to provide clinical standards to validate the liquid biopsy as a clinical biomarker in well-designed and sufficiently powered multicenter studies.

show abstract

Multi-Purpose Utility of Circulating Plasma DNA Testing in Patients with Advanced Cancers

Cited by 133 publications

References 28 publications

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

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

Circulating Cell-Free Tumor DNA Analysis of 50 Genes by Next-Generation Sequencing in the Prospective MOSCATO Trial

Circulating Tumor DNA as a Liquid Biopsy for Cancer

Contact Info

Product

Resources

About