Clinical value of ctDNA in upper-GI cancers: A systematic review and meta-analysis

Creemers, Aafke; Krausz, Sarah; Strijker, Marin; Wel, Myrtle J. van der; Soer, Eline C.; Reinten, Roy J.; Besselink, Marc G.; Wilmink, Johanna W.; Vijver, Marc J. van de; Noesel, Carel J. M. van; Verheij, Joanne; Meijer, Sybren L.; Dijk, Frederike; Bijlsma, Maarten F.; Oijen, Martijn G.H. van; Laarhoven, Hanneke W. M. van

doi:10.1016/j.bbcan.2017.08.002

Cited by 54 publications

(51 citation statements)

References 53 publications

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“…Some studies have been performed evaluating cell free DNA in plasma/serum of GAC patients. 31,39,41,[48][49][50][51][52] In our study, 40% of the patients had the same tumor-biopsy TP53 mutations found in their plasma samples. In agreement with the literature, tumor-derived mutation frequencies in our cohort were higher in patients with stages III and IV.…”

Section: Discussionsupporting

confidence: 71%

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Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: Possible implications for liquid biopsies and patient follow‐up

Pizzi

Bartelli

Pelosof

et al. 2019

Intl Journal of Cancer

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Whereas cancer patients have benefited from liquid biopsies, the scenario for gastric adenocarcinoma (GAC) is still dismal. We used next‐generation deep sequencing of TP53—a highly mutated and informative gene in GAC—to assess mutations in tumor biopsies, plasma (PL) and stomach fluids (gastric wash—GW). We evaluated their potential to reveal tumor‐derived mutations, useful for monitoring mutational dynamics at diagnosis, progression and treatment. Exon‐capture libraries were constructed from 46 patients including tumor biopsies, GW and PL pre and post‐treatment (196 samples), with high vertical coverage >8,000×. At diagnosis, we detected TP53 mutations in 15/46 biopsies (32.6%), 7/46 GW‐ (15.2%) and 6/46 PL‐samples (13%). Biopsies and GW were concordant in 38/46 cases (82.6%) for the presence/absence of mutations and, furthermore, four GW‐exclusive mutations were identified, suggesting tumor heterogeneity. Considering the combined analysis of GW and PL, TP53 mutations found in biopsies were also identified in 9/15 (60%) of cases, the highest detection level reported for GAC. Our study indicates that GW could be useful to track DNA alterations, especially if anchored to a comprehensive gene‐panel designed for this malignancy.

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Section: Discussionsupporting

confidence: 71%

“…Some studies have been performed evaluating cell free DNA in plasma/serum of GAC patients . In our study, 40% of the patients had the same tumor‐biopsy TP53 mutations found in their plasma samples.…”

Section: Discussionmentioning

confidence: 51%

Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: Possible implications for liquid biopsies and patient follow‐up

Pizzi

Bartelli

Pelosof

et al. 2019

Intl Journal of Cancer

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“…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 . Lastly, it has been suggested that ctDNA is a surrogate marker for tumor burden, but very few studies have formally assessed the relationship between ctDNA quantity and 3D tumor volumes, and never in PDAC .…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8][9] In addition, ctDNA detection appears to have a strong prognostic value in patients with PDAC, but validation of this finding is required. 7,10 Lastly, it has been suggested that ctDNA is a surrogate marker for tumor burden, but very few studies have formally assessed the relationship between ctDNA quantity and 3D tumor volumes, and never in PDAC. [11][12][13] As PDAC is comprised of dense desmoplastic stroma with comparatively few tumor cells, the relationship between tumor volume and ctDNA quantity is difficult to predict.…”

Section: Introductionmentioning

confidence: 99%

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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“…A recent meta‐analysis by Creemers et al . () showed that the ctDNA in pancreatic cancer is significantly associated with a poor prognosis. In contrast, Bernard et al .…”

Section: Clinical Application Of Ctdna In Pdacmentioning

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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Clinical value of ctDNA in upper-GI cancers: A systematic review and meta-analysis

Cited by 54 publications

References 53 publications

Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: Possible implications for liquid biopsies and patient follow‐up

Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: Possible implications for liquid biopsies and patient follow‐up

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

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

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