Circulating Nucleic Acids Are Associated With Outcomes of Patients With Pancreatic Cancer

Bernard, Vincent; Kim, Dong U.; Lucas, F. Anthony San; Castillo, Jonathan; Allenson, Kelvin; Mulu, Feven C.; Stephens, Bret M.; Huang, Jonathan; Semaan, Alexander; Guerrero, Paola A.; Kamyabi, Nabiollah; Zhao, Jun; Hurd, Mark W.; Koay, Eugene J.; Taniguchi, Cullen M.; Herman, Joseph M.; Javle, Milind; Wolff, Robert A.; Katz, Matthew H.; Varadhachary, Gauri R.; Maitra, Anirban; Alvarez, Hector A.

doi:10.1053/j.gastro.2018.09.022

Cited by 312 publications

(313 citation statements)

References 37 publications

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“…Other studies demonstrated that, among various cancer types, concordance was variable with a range of ~70–98%, depending on the gene(s) examined . Several previous studies evaluated the concordance of KRAS alterations between tissue and ctDNA and found overall concordance to range 67–96% . These studies did not evaluate the impact of time interval between tissue biopsy and blood draw, nor did they examine the correlation with site of biopsy or the association with outcome for discordant vs .…”

Section: Introductionmentioning

confidence: 99%

“…8,14,15 Several previous studies evaluated the concordance of KRAS alterations between tissue and ctDNA and found overall concordance to range 67-96%. 6,[16][17][18] These studies did not evaluate the impact of time interval between tissue biopsy and blood draw, nor did they examine the correlation with site of biopsy or the association with outcome for discordant vs. concordant KRAS alterations.…”

Section: Introductionmentioning

confidence: 99%

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Temporal and spatial effects and survival outcomes associated with concordance between tissue and blood KRAS alterations in the pan‐cancer setting

Mardinian

Okamura

Kato

et al. 2019

Intl Journal of Cancer

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We investigated the impact of time interval, primary vs. metastatic biopsy site, variant allele fraction (VAF) and histology on concordance of KRAS alterations in tissue vs. circulating tumor DNA (ctDNA), and association of concordance with survival. Blood and tissue were evaluated by next‐generation sequencing in 433 patients with diverse cancers. Altogether, 101 patients (23.3%) had KRAS alterations: 56, ctDNA (12.9%); 81, tissue (18.7%); and 36, both (8.3%). The overall blood and tissue concordance rate for KRAS alterations was 85%, but was mainly driven by the large negative/negative subset. Therefore, specificity of one test for the other was high (88.1–94.3%), while sensitivity was not high (44.4–64.3%) and was lower still in patients with >6 vs. ≤2 months between blood and tissue sampling (31.0–40.9% vs. 51.2–84.0%; p = 0.14 time interval‐dependent sensitivity of blood for tissue; p = 0.003, tissue for blood). Positive concordance rate for KRAS alterations was 57.1% vs. 27.4% (colorectal vs. noncolorectal cancer; p = 0.01), but site of biopsy (primary vs. metastatic) and VAF (%ctDNA) was not impactful. The presence of KRAS alterations in both tests was independently associated with shorter survival from diagnosis (hazard ratio, 1.72; 95% confidence interval, 1.04–2.86) and from recurrent/metastatic disease (1.70; 1.03–2.81). Positive concordance of KRAS alterations between ctDNA and tissue was negatively affected by a longer time period between blood and tissue sampling and was higher in colorectal cancer than in other malignancies. The presence of KRAS alterations in both tests was an independent prognostic factor for poor survival.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Temporal and spatial effects and survival outcomes associated with concordance between tissue and blood KRAS alterations in the pan‐cancer setting

Mardinian

Okamura

Kato

et al. 2019

Intl Journal of Cancer

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“…In contrast, Bernard et al . () analyzed longitudinal KRAS mutant allele fraction from ctDNA and exosome DNA and determined that longitudinal monitoring through exosome DNA rather than ctDNA provides prognostic information.…”

Section: Clinical Application Of Ctdna In Pdacmentioning

confidence: 99%

“…A recent meta-analysis by Creemers et al (2017) showed that the ctDNA in pancreatic cancer is significantly associated with a poor prognosis. In contrast, Bernard et al (2019) analyzed longitudinal KRAS mutant allele fraction from ctDNA and exosome DNA and determined that longitudinal monitoring through exosome DNA rather than ctDNA provides prognostic information.…”

Section: Prognostic Markermentioning

confidence: 99%

Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA

et al. 2019

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Reliable biomarkers are required to evaluate and manage pancreatic ductal adenocarcinoma. Circulating tumor cells and circulating tumor DNA are shed into blood and can be relatively easily obtained from minimally invasive liquid biopsies for serial assays and characterization, thereby providing a unique potential for early diagnosis, forecasting disease prognosis, and monitoring of therapeutic response. In this review, we provide an overview of current technologies used to detect circulating tumor cells and circulating tumor DNA and describe recent advances regarding the multiple clinical applications of liquid biopsy in pancreatic ductal adenocarcinoma.

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“…These existing data, which may be leveraged to guide treatment sequencing, are clearly rudimentary. However, we and others are investigating assays of circulating tumor cells, nucleic acids, and exosomes that may quantify and characterize occult metastatic disease and more accurately predict the role of local therapies . Our group also has defined an imaging biomarker that can be evaluated using routine computed tomographic images and may be used to stratify patients’ tumors into distinct biophysical subtypes .…”

Section: Comparison Of Possible Trial Designs For Patients With Brpcmentioning

confidence: 99%

Borderline resectable pancreatic cancer—At the crossroads of precision medicine

Katz

Varadhachary

2019

Cancer

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Circulating Nucleic Acids Are Associated With Outcomes of Patients With Pancreatic Cancer

Abstract: In a prospective cohort of pancreatic cancer patients, we show how longitudinal monitoring using liquid biopsy samples through exoDNA and ctDNA provides both predictive and prognostic information relevant to therapeutic stratification.

Cited by 312 publications

References 37 publications

Temporal and spatial effects and survival outcomes associated with concordance between tissue and blood KRAS alterations in the pan‐cancer setting

Temporal and spatial effects and survival outcomes associated with concordance between tissue and blood KRAS alterations in the pan‐cancer setting

Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA

Borderline resectable pancreatic cancer—At the crossroads of precision medicine

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