Clinical Validation of a Cell-Free DNA Gene Panel

Cheng, Ju; Cao, Yi; Macleay, Allison; Lennerz, Jochen K.; Baig, Aymen; Frazier, Ryan P.; Lee, Vivian; Hu, Krista; Pacula, Maciej; Meneses, Enrique; Robinson, Hayley; Batten, Julie M.; Brastianos, Priscilla K.; Heist, Rebecca S.; Bardia, Aditya; Le, Long P.; Iafrate, A. John

doi:10.1016/j.jmoldx.2019.02.008

Cited by 16 publications

(17 citation statements)

References 39 publications

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“…Among 211 patients with EGFR-mutant NSCLC initiating first-line therapy with an EGFR inhibitor, the positive percentage agreement (sensitivity) of the cobas ctDNA assay for the detection of common sensitizing EGFR mutations present in tissue has been reported at 68-79% 35 . Similar false-negative rates, of ~20%, have been described in the clinical validation of NGS-based assays, both for EGFR mutations and for other targetable genotypes [25][26][27][28][29][30] . This high but imperfect level of sensitivity is believed to be related to variations in the amounts of ctDNA shed into the plasma, with an understandable decline in sensitivity in the presence of negligible amounts of ctDNA.…”

Section: Genotyping Of Ctdnasupporting

confidence: 65%

“…This high PPV means that the detection of sensitizing EGFR mutations in ctDNA can be clinically actionable, even at extremely low AFs. This high level of specificity for targetable genotypes has now been replicated in the clinical validation of targeted NGS-based assays designed for the sensitive detection of a range of variants in plasma DNA, albeit in smaller cohorts [25][26][27][28][29] . The results obtained using a commercially available plasma NGS platform revealed a PPV of 100% in 34 patients with advanced-stage NSCLC, including the detection of alterations in EGFR (n = 27), ALK (n = 5) or BRAF (n = 2) 30 .…”

Section: Genotyping Of Ctdnamentioning

confidence: 87%

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Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice

et al. 2020

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Section: Genotyping Of Ctdnasupporting

confidence: 65%

Section: Genotyping Of Ctdnamentioning

confidence: 87%

Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice

et al. 2020

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“…All this can be achieved by the introduction of this minimally invasive procedure that can be repeated several times throughout the disease progression without arm for the patients. Moreover, liquid biopsies provide a broader genetic characterization of the tumor reflecting its heterogeneity [9,36,40,49] and possibly identify disseminating aggressive clones.…”

Section: Of 20mentioning

confidence: 99%

“…Nevertheless, through the analysis of tumor-specific alterations, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs) [40], and methylation alterations [16,57,59], one can identify tumor-derived DNA-ctDNA, among the total pool of cfDNA, providing a much more accurate form of cancer genotyping and, consequently, of diagnosis. Importantly, these (epi)genetic alterations seem to be highly concordant in blood ctDNA and in corresponding tumor tissues in a variety of cancers, including lung [17,29,42], breast [35], colorectal [17,44,50,52], pancreatic [32], liver [57], esophageal [17], gastric [6,43], and ovarian [17] cancers.…”

Section: Liquid Biopsies For Diagnosis and Tumor Profilingmentioning

confidence: 99%

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Liquid Biopsies: Applications for Cancer Diagnosis and Monitoring

Martins

Ribeiro

Jorge

et al. 2021

Genes

102

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The minimally—or non-invasive detection of circulating tumor-derived components in biofluids, such as blood, liquid biopsy is a revolutionary approach with significant potential for the management of cancer. Genomic and transcriptomic alterations can be accurately detected through liquid biopsies, which provide a more comprehensive characterization of the heterogeneous tumor profile than tissue biopsies alone. Liquid biopsies could assist diagnosis, prognosis, and treatment selection, and hold great potential to complement current surveilling strategies to monitor disease evolution and treatment response in real-time. In particular, these are able to detect minimal residual disease, to predict progression, and to identify mechanisms of resistance, allowing to re-orient treatment strategies in a timelier manner. In this review we gathered current knowledge regarding the role and potential of liquid biopsies for the diagnosis and follow-up of cancer patients. The presented findings emphasize the strengths of liquid biopsies, revealing their chance of improving the diagnosis and monitoring of several tumor types in the near future. However, despite growing evidence supporting their value as a management tool in oncology, some limitations still need to be overcome for their implementation in the routine clinical setting.

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Clinical Utility of Molecular Genetic Cancer Profiling

Joseph¹

2020

Encyclopedia of Life Sciences

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The ability to sequence entire genomes and transcriptomes is revolutionising cancer biology and, more slowly, cancer medicine. The evidence that large‐scale sequencing has clinical utility, that it improves outcomes, is slowly accumulating. A major controversy has centred on whether or not all tumours refractory to standard therapy should undergo therapy selection by molecular genetic cancer profiling (MGCP). Despite several completed or ongoing clinical trials, this issue is not settled; however, other forces now ensure that MGCP will become a routine diagnostic tool. Biopsies are becoming smaller, providing greater safety for patients, but yielding less DNA/RNA while there are now sufficiently many molecularly targeted agents approved in major cancers that testing by single‐gene assays is no longer practical or economical. Key Concepts A clinical test does not have inherent clinical utility. The clinical utility of molecule genetic cancer profiling varies with the intended clinical use: diagnosis, prognosis, treatment selection, and cancer risk assessment. Assessment of clinical utility does NOT include consideration of cost. There is incomplete consensus on which genes should be in a molecular genetic cancer profile but in practice panels cover at most several hundred genes (ie much smaller than an exome). Most molecular genetic cancer profiling has used tumor genomic DNA but assays are increasingly including analysis of RNA for translocation detection and gene expression. The traditional method for determining clinical utility, the randomized clinical trial, is evolving to facilitate screening of many genes and many molecularly targeted agents rapidly. Large‐scale clinical trials are underway to assess the clinical utility of applying molecular genetic panels to all cancers in a histology‐agnostic fashion. Clinical trials for molecularly targeted agents predicted to be beneficial by molecular genetic cancer profiling are always conducted on patients with advanced disease who have already failed several established ‘lines of therapy’. Likelihood of response to a new class of therapy, immune checkpoint inhibitors, might be predicted by microsatellite instability and, possibly, by the Tumor Mutation Burden. Response to another new class of therapy, CAR‐T cells, might be mutation agnostic.

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Clinical Validation of a Cell-Free DNA Gene Panel

Cited by 16 publications

References 39 publications

Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice

Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice

Liquid Biopsies: Applications for Cancer Diagnosis and Monitoring

Clinical Utility of Molecular Genetic Cancer Profiling

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