Prognostic value of circulating cell-free DNA in patients with pancreatic cancer: A systemic review and meta-analysis

Chen, Linyan; Zhang, Yi; Yuan, Cheng; Zhang, Dan; Zhu, Sha; Ma, Xuelei

doi:10.1016/j.gene.2018.09.029

Cited by 47 publications

(43 citation statements)

References 43 publications

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“…Whether one measurement confers more accurate prognostic information than the other requires further investigation. The prognostic value of ctDNA for OS ( p = 0.005) is in line with the results of a recent meta‐analysis of ctDNA in PDAC . In our study, ctDNA was an predictor of OS after adjustment for CA19.9 and treatment regimen, while CA19.9 was not an independent predictor after adjustment for ctDNA, an observation also reported by others .…”

Section: Discussionsupporting

confidence: 92%

“…This provides a good representation of the patient population but might have resulted in lower detection rates. In most other studies with mPDAC patients, patient flow and selection methods were unclear, hampering comparisons . Our finding that higher ctDNA detection rates occurred in patients with liver metastases of PDAC has also been reported for colorectal cancer .…”

Section: Discussionmentioning

confidence: 58%

“…The ctDNA detection rate of 46% in the total cohort and 75% in patients with high tumor volume and liver metastases are within the ranges reported in literature. Studies reporting exclusively on mPDAC showed detection rates of 29.3–33% . When various tumor stages were studied, a sensitivity between 38.8% and 86.1% was determined for those patients with metastatic disease .…”

Section: Discussionmentioning

confidence: 99%

“…As illustrated by the joint review of the American Society of Clinical Oncology and the College of American Pathologists, questions remain about the validity and reproducibility of ctDNA analysis, hampering clinical application . ctDNA detection rates vary widely depending on cancer type and analysis technique; for mPDAC, rates between 38.8% and 86.1% have been reported . In addition, ctDNA detection appears to have a strong prognostic value in patients with PDAC, but validation of this finding is required .…”

Section: Introductionmentioning

confidence: 99%

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Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma

Strijker

Soer

Pastena

et al. 2019

Intl Journal of Cancer

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Circulating tumor DNA (ctDNA) is assumed to reflect tumor burden and has been suggested as a tool for prognostication and follow‐up in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). However, the prognostic value of ctDNA and its relation with tumor burden has yet to be substantiated, especially in mPDAC. In this retrospective analysis of prospectively collected samples, cell‐free DNA from plasma samples of 58 treatment‐naive mPDAC patients was isolated and sequenced using a custom‐made pancreatobiliary NGS panel. Pathogenic mutations were detected in 26/58 (44.8%) samples. Cross‐check with droplet digital PCR showed good agreement in Bland–Altman analysis (p = 0.217, nonsignificance indicating good agreement). In patients with liver metastases, ctDNA was more frequently detected (24/37, p < 0.001). Tumor volume (3D reconstructions from imaging) and ctDNA variant allele frequency (VAF) were correlated (Spearman's ρ = 0.544, p < 0.001). Median overall survival (OS) was 3.2 (95% confidence interval [CI] 1.6–4.9) versus 8.4 (95% CI 1.6–15.1) months in patients with detectable versus undetectable ctDNA (p = 0.005). Both ctDNA VAF and tumor volume independently predicted OS after adjustment for carbohydrate antigen 19.9 and treatment regimen (hazard ratio [HR] 1.05, 95% CI 1.01–1.09, p = 0.005; HR 1.00, 95% CI 1.01–1.05, p = 0.003). In conclusion, our study showed that ctDNA detection rates are higher in patients with larger tumor volume and liver metastases. Nevertheless, measurements may diverge and, thus, can provide complementary information. Both ctDNA VAF and tumor volume were strong predictors of OS.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma

Strijker

Soer

Pastena

et al. 2019

Intl Journal of Cancer

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“…Kras is the most frequently reported oncogenic mutation in ctDNA of pancreatic cancer with the rate ranging from 65% to 85% . Several studies identified that Kras mutation in ctDNA plays a prognostic role in pancreatic cancer . However, Kras‐related target therapy or immune treatment almost failed to improve survival in clinical trials …”

Section: Introductionmentioning

confidence: 99%

Kras mutation correlating with circulating regulatory T cells predicts the prognosis of advanced pancreatic cancer patients

Luo

Jin

et al. 2020

Cancer Medicine

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Purpose Kras mutation and abnormal immune status are associated with pancreatic cancer development and progression. In this study, we evaluated the Kras mutation status in circulating tumor DNA and circulating T cell subsets in a cohort of advanced pancreatic cancer patients. Methods Samples were retrospectively obtained from a series of 210 pathological advanced pancreatic cancer patients between 2012 and 2014. The Kras mutation status was detected in cell‐free circulating tumor DNA (ctDNA) by ddPCR and circulating T cell subsets were analyzed by flow cytometry. Results Univariate analysis found that tumor node metastasis (TNM) stage, chemotherapy, circulating regulatory T cells, CA19‐9 levels, CA125 levels, and KrasG12D and KrasG12V mutations were significantly related to overall survival in advanced pancreatic cancer patients. Multivariate analysis identified that TNM stage (P = .03, HR:1.422), Tregs (P = .004, HR:1.522), CA19‐9 levels (P = .009, HR:1.488), KrasG12D mutation (P = .044, HR:1.353), and KrasG12V mutation (P = .001, HR:1.667) were independent prognostic markers. Furthermore, we found that KrasG12V mutation in ctDNA was correlated with high circulating proportion of Tregs, and patients with both KrasG12V mutation and high levels of Tregs were associated with extremely poor survival in advanced pancreatic cancer. Conclusion KrasG12V mutation was associated with high circulating regulatory T cell levels, and both of them predicted worse prognosis in advanced pancreatic cancer patients.

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Survival and Late Morbidity after Resection of Pancreatic Cancer

Yeo

2023

The Pancreas

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Prognostic value of circulating cell-free DNA in patients with pancreatic cancer: A systemic review and meta-analysis

Cited by 47 publications

References 43 publications

Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma

Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma

Kras mutation correlating with circulating regulatory T cells predicts the prognosis of advanced pancreatic cancer patients

Survival and Late Morbidity after Resection of Pancreatic Cancer

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