Meta-Analysis of Circulating Cell-Free DNA’s Role in the Prognosis of Pancreatic Cancer

Milin-Lazović, Jelena; Madzarevic, Petar; Rajović, Nina; Djordjević, Vladimir; Milic, Nikola; Pavlović, Sonja; Veljković, Nevena; Milić, Nataša; Radenković, Dejan

doi:10.3390/cancers13143378

Cited by 9 publications

(7 citation statements)

References 84 publications

(240 reference statements)

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“…The prognostic value of ctDNA has been evaluated in a recent meta-analysis of 48 studies of over 3000 patients with different stages of PC. This study found that the detection of KRAS mutations via ctDNA has a negative impact on OS and PFS in PC (HR = 2.42; 95% CI = 1.95 - 2.99 and HR = 2.46; 95% CI = 2.01 - 3.00, respectively) ( 94 ). In localized PC, detection of ctDNA preoperatively is associated with poorer RFS (HR = 4.1; P = 0.002) and OS (HR = 4.0; P = 0.003) ( 95 ).…”

Section: Pancreatico-biliary Cancermentioning

confidence: 93%

“…Collectively, several studies have shown that ctDNA increase tends to precede clinical progression as determined by imaging and serum Ca19.9 level by a few months ( 100 – 102 ). In a meta-analysis of studies on patients with detectable KRAS before treatment, conversion to undetectable KRAS after treatment is associated with better prognosis ( 94 ). ctDNA has also been used to track other cancer-specific mutations such as TP53 , APC , ATM , FBXW7 , SMAD4 , CDKN2A and other variants ( 101 , 103 ).…”

Section: Pancreatico-biliary Cancermentioning

confidence: 99%

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Clinical applications of circulating tumor-derived DNA in the management of gastrointestinal cancers – current evidence and future directions

Lam

Johnson²,

Lam³

et al. 2022

Front. Oncol.

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Advances in Next Generation Sequencing (NGS) technologies have enabled the accurate detection and quantification of circulating tumor-derived (ct)DNA in most gastrointestinal (GI) cancers. The prognostic and predictive utility of ctDNA in patiets with different stages of colorectal (CRC), gastro-esophageal (GEC) and pancreaticobiliary cancers (PBC) are currently under active investigation. The most mature clinical data to date are derived from studies in the prognostic utility of personalized ctDNA-based NGS assays in the detection of minimal residual disease (MRD) and early recurrence after surgery in CRC and other GI cancers. These findings are being validated in several prospective studies which are designed to test if ctDNA could outperform conventional approaches in guiding adjuvant chemotherapy, and in post-operative surveillance in some GI cancers. Several adaptive studies using ctDNA as a screening platform are also being used to identify patients with actionable genomic alterations for clinical trials of targeted therapies. In the palliative setting, ctDNA monitoring during treatment has shown promise in the detection and tracking of clonal variants associated with acquired resistance to targeted therapies and immune-checkpoint inhibitors (ICI). Moreover, ctDNA may help to guide the therapeutic re-challenge of targeted therapies in patients who have prior exposure to such treatment. This review will examine the most updated research findings on ctDNA as a biomarker in CRC, GEC and PBCs. It aims to provide insights into how the unique strengths of this biomarker could be optimally leveraged in improving the management of these GI cancers.

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Section: Pancreatico-biliary Cancermentioning

confidence: 93%

Section: Pancreatico-biliary Cancermentioning

confidence: 99%

Clinical applications of circulating tumor-derived DNA in the management of gastrointestinal cancers – current evidence and future directions

Lam

Johnson²,

Lam³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…KRAS mutations are the most common target used for PDAC detection. Many studies have reviewed the available data in the literature and shown this [ 165 , 182 , 183 , 184 , 185 ]. KRAS mutations are rarely found in clones during age-associated clonal hematopoiesis, such as in DNMT3A, TET2, JAK2, ASXL1, TP53 , GNAS, PPM1D, BCORL1, and SF3B1.…”

Section: Circulating Cell-free Tumoral Dna (Ctdna)mentioning

confidence: 99%

Circulating Cell-Free Nucleic Acids as Biomarkers for Diagnosis and Prognosis of Pancreatic Cancer

et al. 2023

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A lack of reliable early diagnostic tools represents a major challenge in the management of pancreatic cancer (PCa), as the disease is often only identified after it reaches an advanced stage. This highlights the urgent need to identify biomarkers that can be used for the early detection, staging, treatment monitoring, and prognosis of PCa. A novel approach called liquid biopsy has emerged in recent years, which is a less- or non-invasive procedure since it focuses on plasmatic biomarkers such as DNA and RNA. In the blood of patients with cancer, circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) have been identified such as DNA, mRNA, and non-coding RNA (miRNA and lncRNA). The presence of these molecules encouraged researchers to investigate their potential as biomarkers. In this article, we focused on circulating cfNAs as plasmatic biomarkers of PCa and analyzed their advantages compared to traditional biopsy methods.

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“…The detection of mut- KRAS in aPDAs indicates poorer outcomes, as demonstrated by multiple studies [ 64 , 67 , 73 , 74 , 76 , 80 , 82 ]. A recent meta-analysis of 48 studies examined the prognostic role of mut- KRAS detection in cfDNA to provide a more comprehensive summary [ 83 ]. The study examined 3524 patients across all stages of the disease, before and after treatment (both surgical and pharmacologic).…”

Section: Prognostic Value Of Cfdna In Pdamentioning

confidence: 99%

Is Cell-Free DNA Testing in Pancreatic Ductal Adenocarcinoma Ready for Prime Time?

Sheel

Addison

Nuguru

et al. 2022

Cancers

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Cell-free DNA (cfDNA) testing currently does not have a significant role in PDA management: it is insufficient to diagnose PDA, and its use is primarily restricted to identifying targetable mutations (if tissue is insufficient or unavailable). cfDNA testing has the potential to address critical needs in PDA management, such as pre-operative risk stratification (POR), prognostication, and predicting (and monitoring) treatment response. Prior studies have focused primarily on somatic mutations, specifically KRAS variants, and have shown limited success in addressing prognosis and POR. Recent studies have demonstrated the importance of other less prevalent mutations (ERBB2 and TP53), but no studies have provided reliable mutation panels for clinical use. Methylation aberrations in cfDNA (epigenetic markers) in PDA have been relatively less explored. However, early evidence has suggested they offer diagnostic and, to some extent, prognostic value. The inclusion of epigenetic markers of cfDNA adds another dimension to genomic testing and may open new therapeutic avenues beyond addressing critical areas of need in PDA treatment. For cfDNA to substantially influence PDA management, concerted efforts are required to include less frequent mutations and epigenetic markers. Furthermore, relying on KRAS mutations for PDA management will always be inadequate.

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Meta-Analysis of Circulating Cell-Free DNA’s Role in the Prognosis of Pancreatic Cancer

Cited by 9 publications

References 84 publications

Clinical applications of circulating tumor-derived DNA in the management of gastrointestinal cancers – current evidence and future directions

Clinical applications of circulating tumor-derived DNA in the management of gastrointestinal cancers – current evidence and future directions

Circulating Cell-Free Nucleic Acids as Biomarkers for Diagnosis and Prognosis of Pancreatic Cancer

Is Cell-Free DNA Testing in Pancreatic Ductal Adenocarcinoma Ready for Prime Time?

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