Cell-free circulating tumor DNA somatic alteration burden and its impact on survival in metastatic cancer.

Background: Circulating tumor DNA (ctDNA) offers high sensitivity and specificity in metastatic cancer. However, many ctDNA assays rely on specific mutations in recurrent genes or require the sequencing of tumor tissue, difficult to do in a metastatic disease. The purpose of this study was to define the predictive and prognostic values of the whole-genome sequencing (WGS) of ctDNA in metastatic breast cancer (MBC). Methods: Plasma from 25 patients with MBC were taken at the baseline, prior to treatment (T0), one week (T1) and two weeks (T2) after treatment initiation and subjected to low-pass WGS. DNA copy number changes were used to calculate a Genomic Instability Number (GIN). A minimum predefined GIN value of 170 indicated detectable ctDNA. GIN values were correlated with the treatment response at three and six months by Response Evaluation Criteria in Solid Tumours assessed by imaging (RECIST) criteria and with overall survival (OS). Results: GIN values were detectable (>170) in 64% of patients at the baseline and were significantly prognostic (41 vs. 18 months OS for nondetectable vs. detectable GIN). Detectable GIN values at T1 and T2 were significantly associated with poor OS. Declines in GIN at T1 and T2 of > 50% compared to the baseline were associated with three-month response and, in the case of T1, with OS. On the other hand, a rise in GIN at T2 was associated with a poor response at three months. Conclusions: Very early measurements using WGS of cell-free DNA (cfDNA) from the plasma of MBC patients provided a tumor biopsy-free approach to ctDNA measurement that was both predictive of the early tumor response at three months and prognostic.

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Potentials, challenges and limitations of a molecular characterization of circulating tumor DNA for the management of cancer patients

LaboratoriumsMedizin ◽

10.1515/labmed-2016-0049 ◽

2016 ◽

Vol 40 (5) ◽

Author(s):

Peter Ulz ◽

Armin Gerger ◽

Jelena Belic ◽

Ellen Heitzer

Keyword(s):

Cancer Patients ◽

Residual Disease ◽

Metastatic Cancer ◽

Circulating Tumor Dna ◽

Disease Assessment ◽

Tumor Evolution ◽

Non Invasive ◽

New Findings ◽

Technological Improvements ◽

Tumor Dna

Abstract:A liquid profiling, i.e. the analysis of cell-free circulating tumor DNA (ctDNA), enables a continuous non-invasive monitoring of tumor-specific changes during the entire course of the disease with respect to early detection, identification of minimal residual disease, assessment of treatment response and monitoring tumor evolution. Technological improvements, advances in understanding the nature of ctDNA, the implementation of ctDNA analyses in clinical trials as well as efforts for the establishment of benchmarks, will bring an actual widespread clinic use within reach in the near future. However, despite this progress there are still hurdles that have to be overcome, which are discussed in this review. Moreover, present knowledge and new findings about the biology of ctDNA as well as selected potential clinical applications for metastatic cancer patients are pointed out.

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Analysis of cell-free circulating tumor DNA in 419 patients with glioblastoma and other primary brain tumors

CNS Oncology ◽

10.2217/cns-2018-0015 ◽

2019 ◽

Vol 8 (2) ◽

pp. CNS34 ◽

Cited By ~ 26

Author(s):

David E Piccioni ◽

Achal Singh Achrol ◽

Lesli A Kiedrowski ◽

Kimberly C Banks ◽

Najee Boucher ◽

...

Keyword(s):

Brain Tumors ◽

Genomic Analysis ◽

Circulating Tumor Dna ◽

Single Nucleotide Variants ◽

Viable Option ◽

Single Nucleotide ◽

Primary Brain Tumors ◽

Somatic Alteration ◽

Tumor Sequencing ◽

Tumor Dna

Aim: Genomically matched trials in primary brain tumors (PBTs) require recent tumor sequencing. We evaluated whether circulating tumor DNA (ctDNA) could facilitate genomic interrogation in these patients. Methods: Data from 419 PBT patients tested clinically with a ctDNA NGS panel at a CLIA-certified laboratory were analyzed. Results: A total of 211 patients (50%) had ≥1 somatic alteration detected. Detection was highest in meningioma (59%) and gliobastoma (55%). Single nucleotide variants were detected in 61 genes, with amplifications detected in ERBB2, MET, EGFR and others. Conclusion: Contrary to previous studies with very low yields, we found half of PBT patients had detectable ctDNA with genomically targetable off-label or clinical trial options for almost 50%. For those PBT patients with detectable ctDNA, plasma cfDNA genomic analysis is a clinically viable option for identifying genomically driven therapy options.

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